Capacities

What declines with age, how fast, and what moves it back.

Blood tests are one slice of the landscape. Strength, aerobic capacity, vagal tone, the senses, processing speed, learning, emotional stability, balance, sleep and immune response are capacities too, and so are the tissue properties beneath them: muscle-fibre size, ejection fraction, flow-mediated dilation, brain and vessel structure. Each can be measured. For every one, this page lists the change with age, its link to healthspan, and the remedies with the size of the shift they produced.

Framework: Halma M, Marik P, Varon J, Tuszynski J. Reversing Decline in Aging Muscles: Expected Trends, Impacts and Remedies. J Funct Morphol Kinesiol. 2025;10(1):29., applied beyond muscle. Every literature number is copied from the linked PubMed abstract; units are the abstract's own. 76 of 76 capacities and parameters have evidence so far, from 1,266 sources, and all 238 biomarkers with catalogue data are tabulated at the end.

Musculoskeletal · Muscle and nerve physiology · Cardiorespiratory · Cardiac structure and function · Vascular · Autonomic · Brain structure · Sensory · Cognitive · Emotional · Motor performance · Sleep and recovery · Immune · Metabolic · Body composition and tissue · Biomarkers

Each item is collapsed; open it for its trajectory with age, by default and given an intervention, and the evidence behind it.

Musculoskeletal

Muscle mass Appendicular lean mass (DXA) (kg) · capacity

1 4 7

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↓ 36% (36 to 48) Trunk muscle thickness, older vs younger adults · Rectus abdominis, internal and external oblique thickness 36% to 48% smaller in older (>=50 y) than younger adults; value is the lower bound of the stated range
ages older (>=50 y) vs younger adults · adults >=50 y (best-evidence synthesis) · systematic review · Cuellar WA, et al. Physiotherapy. 2017. PMID 27667760

Link to healthspan (4)

↑ ratio 2.97 (2.15 to 4.08) Sarcopenia and Alzheimer's disease → dementia (Alzheimer's disease) · Pooled odds ratio, sarcopenia vs no sarcopenia; MCI pooled OR 1.58 (1.42-1.76), non-AD dementia 1.68 (1.09-2.58)
adults >=50 y, 77 studies (mostly cross-sectional) · n = 92,058 · meta analysis · Amini N, et al. J Cachexia Sarcopenia Muscle. 2024. PMID 38715252
↑ ratio 2.3 (2.01 to 2.63) Sarcopenia and mortality in cirrhosis → mortality · Adjusted hazard ratio, sarcopenia vs no sarcopenia; per-unit quantitative muscle mass index aHR 0.95 (0.93-0.98)
patients with cirrhosis, 22 cohort studies · n = 6,965 · meta analysis · Tantai X, et al. J Hepatol. 2022. PMID 34785325
↑ ratio 1.69 (1.28 to 2.23) Low appendicular skeletal muscle mass index and all-cause mortality (KNHANES) → all-cause mortality · Total natural direct effect of low ASMI on all-cause mortality, hazard ratio, mediation analysis
Korean adults, KNHANES 2008-2011 · n = 14,449 · prospective cohort · Moon S, et al. J Cachexia Sarcopenia Muscle. 2025. PMID 40230053
↑ ratio 2.08 (1.57 to 2.76) Low appendicular skeletal muscle mass index and all-cause mortality (NHANES) → all-cause mortality · Total natural direct effect of low ASMI on all-cause mortality, hazard ratio, mediation analysis
US adults, NHANES 1999-2006 and 2011-2018 · n = 8,036 · prospective cohort · Moon S, et al. J Cachexia Sarcopenia Muscle. 2025. PMID 40230053

Remedy and magnitude (7)

↑ 8.9% High-intensity interval training (muscle fibre cross-sectional area) · Percentage increase in fibre CSA after HIT (8.9 +/- 4.9%); endurance training 6.5 +/- 3.5%, sprint interval training 11.9 +/- 15.1%
adults in exercise training studies · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025. PMID 39390310
↑ SMD 0.45 Nutrition interventions (Mediterranean diet, antioxidant-rich foods, protein) · Standardised mean difference for muscle mass across lifestyle RCTs; no confidence interval reported
adults 50+, 35 RCTs · n = 25,000 · meta analysis · Joshi S, et al. Invest Educ Enferm. 2025. PMID 41289530
↑ 1.08 kg (0.77 to 1.38) Creatine supplementation (lean tissue mass) · Mean difference in lean tissue mass, creatine vs placebo
older adults and adults with chronic disease at risk of functional disability, 33 RCTs · n = 1,076 · meta analysis · Davies TW, et al. JPEN J Parenter Enteral Nutr. 2024. PMID 38417175
↑ 0.34 kg (0.1 to 0.58) Protein supplementation after exercise (skeletal muscle mass) · Mean difference vs placebo for post-exercise protein timing; fat-free mass MD 0.54 kg (0.10, 0.99)
protein taken after exercise, alongside resistance training · adults undergoing resistance training, 116 RCTs · n = 4,711 · meta analysis · Zhou HH, et al. Int J Sport Nutr Exerc Metab. 2024. PMID 38039960
SMD -0.01 (-0.16 to 0.18) Concurrent aerobic plus strength training vs strength training alone (hypertrophy) · Standardised mean difference for muscle hypertrophy, concurrent vs strength-only training of at least 4 weeks
>=4 weeks supervised training · healthy adults, 43 studies · meta analysis · Schumann M, et al. Sports Med. 2022. PMID 34757594
↑ SMD 0.22 (0.14 to 0.3) Increased daily protein intake with resistance exercise (lean body mass) · Standardised mean difference in lean body mass, higher vs lower daily protein, studies with resistance exercise (62 studies)
1.2-1.59 g protein/kg/day (>=65 y); >=1.6 g/kg/day (<65 y) · healthy non-obese adults, 74 RCTs · meta analysis · Nunes EA, et al. J Cachexia Sarcopenia Muscle. 2022. PMID 35187864
↑ 0.3 kg (0.09 to 0.52) Protein supplementation during resistance training (fat-free mass) · Change in fat-free mass with protein supplementation vs no supplementation during RET of at least 6 weeks; effect smaller with increasing age (-0.01 kg per year)
no further FFM gain above ~1.62 g protein/kg/day · healthy adults, 49 RCTs · n = 1,863 · meta analysis · Morton RW, et al. Br J Sports Med. 2018. PMID 28698222

Muscle strength Hand-grip strength (kg) · capacity on the landscape

2 6 13

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, NHANES adults, 2013-2014 (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Illustration, not a forecast: the effect is applied at once from the chosen age, assumed to persist and to add to the default, with the rate of ageing unchanged. Trial effects were measured over weeks to months in selected groups.

Change with age (2)

↓ -2.5 kg Median, ages 40–59 vs 20–39 catalogue · 41 → 38.5 (-6%)
ages 40–59 vs 20–39 · NHANES adults, 2013-2014 · n = 4,500 · cross sectional · National Center for Health Statistics. National Health and Nutrition Examination Survey: 2017-2018 laboratory data. Hyattsville, MD: Centers for Disease Control and Prevention; 2020. doi 10.15620/cdc:106318
↓ -9.5 kg Median, ages 60+ vs 20–39 catalogue · 41 → 31.5 (-23%)
ages 60+ vs 20–39 · NHANES adults, 2013-2014 · n = 4,550 · cross sectional · National Center for Health Statistics. National Health and Nutrition Examination Survey: 2017-2018 laboratory data. Hyattsville, MD: Centers for Disease Control and Prevention; 2020. doi 10.15620/cdc:106318

Link to healthspan (6)

↑ ratio 1.51 (1.34 to 1.7) Low handgrip strength and worsening activities of daily living → disability (ADL dependence) · Pooled odds ratio, low vs normal handgrip strength; IADL 1.59 (1.04-2.31)
adults >=65 y, longitudinal cohorts (83 articles) · n = 108,428 · meta analysis · Wang DXM, et al. J Cachexia Sarcopenia Muscle. 2020. PMID 31788969
↓ ratio 0.69 (0.64 to 0.74) Higher handgrip strength and all-cause mortality → all-cause mortality · Hazard ratio, higher vs lower handgrip strength; women 0.60 (0.51-0.69), men 0.69 (0.62-0.77)
apparently healthy adults, 38 cohort studies · n = 1,907,580 · meta analysis · Garcia-Hermoso A, et al. Arch Phys Med Rehabil. 2018. PMID 29425700
↑ ratio 1.27 (1.13 to 1.43) Low grip strength and incident Parkinson disease → Parkinson disease · Hazard ratio for the low-grip-strength frailty criterion; frailty overall HR 1.87 (1.53-2.28)
UK Biobank, British White descent, mean age 56.1 y · n = 314,998 · prospective cohort · Zheng Z, et al. JAMA Neurol. 2023. PMID 36912851
↑ ratio 1.16 (1.15 to 1.17) Grip strength and all-cause mortality, men (UK Biobank) → all-cause mortality · Hazard ratio per 5 kg lower grip strength; cardiovascular mortality 1.22 (1.18-1.26)
UK Biobank adults 40-69 y · n = 502,293 · prospective cohort · Celis-Morales CA, et al. BMJ. 2018. PMID 29739772
↑ ratio 1.2 (1.17 to 1.23) Grip strength and all-cause mortality, women (UK Biobank) → all-cause mortality · Hazard ratio per 5 kg lower grip strength; cardiovascular mortality 1.19 (1.13-1.25)
UK Biobank adults 40-69 y · n = 502,293 · prospective cohort · Celis-Morales CA, et al. BMJ. 2018. PMID 29739772
ratio 0.74 (0.69 to 0.79) PURE Prospective Cohort (17 High-, Middle-, Low-Income Countries) catalogue → mortality · per 1 SD
general · n = 139,691 · prospective cohort · Leong DP, et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet. 2015;386(9990):266-273. PMID 25982160

Remedy and magnitude (13)

↑ SMD 0.23 (0.01 to 0.45) Creatine supplementation · Standardised mean difference in handgrip strength, creatine vs placebo
older adults and adults with chronic disease, 33 RCTs · n = 1,076 · meta analysis · Davies TW, et al. JPEN J Parenter Enteral Nutr. 2024. PMID 38417175
↑ 2.85 kg (0.49 to 5.22) Protein supplementation at night with resistance training · Mean difference in handgrip strength vs placebo for night-time protein timing; leg press MD 12.12 kg (3.26, 20.99)
protein taken at night, alongside resistance training · adults undergoing resistance training, 116 RCTs · n = 4,711 · meta analysis · Zhou HH, et al. Int J Sport Nutr Exerc Metab. 2024. PMID 38039960
↑ 4.19 kg Resistance and balance exercise plus nutrition (sarcopenia) · Mean difference in handgrip strength vs usual care, network meta-analysis; MID 5 kg; no CI reported
12 wk · older adults with sarcopenia, 42 RCTs, median age 72.9 y · n = 3,728 · meta analysis · Shen Y, et al. J Cachexia Sarcopenia Muscle. 2023. PMID 37057640
↑ 1.35 kg Resistance training in adults 60+ · Mean difference in handgrip strength vs control; no CI reported (p = 0.003)
adults >=60 y, 21 studies · n = 1,610 · meta analysis · Khodadad Kashi S, et al. Biol Res Nurs. 2023. PMID 35968662
↑ 4 kg (1.13 to 7) Hand exercise in rheumatoid arthritis (short term) · Right-hand grip strength vs no treatment, SMD 0.46 (0.13 to 0.8) re-expressed as kg; left hand 3.5 kg (0.87 to 6.1)
adults with rheumatoid arthritis of the hand, 3 studies · n = 141 · meta analysis · Williams MA, et al. Cochrane Database Syst Rev. 2018. PMID 30063798
↑ 4.61 kg (2.93 to 6.28) HMB supplementation added to resistance training (sarcopenia) · Difference in change in handgrip strength, HMB vs placebo, both with resistance exercise twice weekly
12 wk · HMB twice daily plus resistance exercise twice a week · adults >=60 y with sarcopenia (HMB n = 18, placebo n = 16) · rct · Yang C, et al. J Nutr Health Aging. 2023. PMID 37248756
↑ 25% (15 to 35) Progressive whole-body resistance training (Heavy compound lifting) catalogue · vs Standard care / no intervention
meta analysis · Peterson MD, et al. Ageing Res Rev. 2010;9:226-237. PMID: 20385254 PMID 20385254
↓ -17.5% (-25 to -10) Prolonged bed rest, immobilization, and neuromuscular disuse catalogue · vs Standard care / no intervention
rct · Kortebein P, et al. JAMA. 2007;297:1772-1774. PMID: 17456818 PMID 17456818
↓ -45% (-60 to -30) Severe protein malnutrition and cancer cachexia syndrome catalogue · vs Standard care / no intervention
clinical guideline · Cruz-Jentoft AJ, et al. Age Ageing. 2019;48:16-31. PMID: 30312372 PMID 30312372
↑ 1.4 kg (-0.27 to 3.07) Hand exercise programme in rheumatoid arthritis (Cochrane review, medium term) catalogue · vs usual care
adults with rheumatoid arthritis of the hands (1 high-quality trial, n=400 at 3-11 months) · n = 400 · meta analysis · Williams MA, et al. The Cochrane database of systematic reviews. 2018. Exercise for rheumatoid arthritis of the hand. PMID 30063798
↑ 1.56 kg (1.13 to 1.99) Baduanjin qigong exercise 60 min x3/week for 24 weeks in sarcopenia catalogue · vs active comparator (resistance training)
24 wk · 60.0 min 3 times per week · 90 older adults aged 60-77 with primary sarcopenia (13 men, 77 women), Chengdu · n = 90 · rct · Wu K, et al. Journal of cachexia, sarcopenia and muscle. 2025. Efficacy of Baduanjin Exercise for Sarcopenia in Older Adults: A 24-Week Randomized Controlled Tr PMID 41371252
↑ 1.7 kg Resistance exercise training 60 min x2/week for 24 weeks in obese older women catalogue · vs no exercise control
24 wk · 60.0 min 2 times per week · 30 obese older women (age 80.6 +/- 4.9, body fat 36%) completing the trial · n = 15 · rct · Kim SW, et al. International journal of environmental research and public health. 2022. Effects of Twenty-Four Weeks of Resistance Exercise Training on Body Com PMID 36361434
↑ 2.5 kg Vitamin C 1000 mg + vitamin E 335 mg daily added to 12-week elastic-band resistance training catalogue · vs placebo plus resistance training
12 wk · 335.0 mg vitamin E (+1000 mg vitamin C) daily · 60 older women aged 60-75 with sarcopenia · n = 60 · rct · Liu X, et al. Medicine. 2025. Effects of vitamins C and E supplementation combined with 12-week resistance training in older women with sarcopenia: A randomized PMID 40859523

Muscle power Leg-extensor power / chair-rise time (W; s) · capacity

5 3 4

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Physical capacity decline rate, 47-year longitudinal cohort, 2.2% per year.

Change with age (5)

↓ -0.05 W/kg per year Relative sit-to-stand power, 30-50 years · Decline in relative 30 s STS power, not significant (p > 0.05)
ages 30-50 y · European adults 20-103 y · n = 9,320 · cross sectional · Alcazar J, et al. J Cachexia Sarcopenia Muscle. 2021. PMID 34216098
↓ -0.1 W/kg per year Relative sit-to-stand power, 50-80 years · Decline in relative (body-mass normalised) 30 s STS power, -0.10 to -0.13 W/kg per year across sexes; value is the smaller rate
ages 50-80 y · European adults 20-103 y (9320 older adults plus 586 young and middle-aged adults) · n = 9,320 · cross sectional · Alcazar J, et al. J Cachexia Sarcopenia Muscle. 2021. PMID 34216098
↓ -0.07 W/kg per year Relative sit-to-stand power, over 80 years · Decline in relative 30 s STS power, -0.07 to -0.08 W/kg per year; value is the smaller rate
ages >80 y · European adults 20-103 y · n = 9,320 · cross sectional · Alcazar J, et al. J Cachexia Sarcopenia Muscle. 2021. PMID 34216098
↑ 0.1 s per year Five-times sit-to-stand time, reference equation · 5TSTS = 3.89 + (0.10 x age) - (0.96 x physical activity), r2 = 27%; 1-minute STS = 61.53 - (0.34 x age) - (3.57 x sex) - (0.33 x BMI)
ages 18-95 y · Portuguese adults without disabilities, 58% female · n = 546 · normative study · Vilarinho R, et al. Physiotherapy. 2024. PMID 38875841
↓ 2.2% per year Physical capacity decline rate, 47-year longitudinal cohort · Rate of decline small initially (0.2%-0.5% per year) rising to 2.2% per year with age; muscle power (Sargent jump) peaked at 27 y in men, 19 y in women
ages 16-63 y · Swedish cohort born 1958, 48% women · n = 427 · prospective cohort · Westerstahl M, et al. J Cachexia Sarcopenia Muscle. 2025. PMID 41243424

Link to healthspan (3)

↑ ratio 14.1 (10.9 to 18.2) Low relative sit-to-stand power and mobility limitation, men → mobility limitation · Age-adjusted odds ratio, relative STS power below 2.6 W/kg vs above
older men 60-103 y · n = 3,159 · cross sectional · Alcazar J, et al. J Cachexia Sarcopenia Muscle. 2021. PMID 34216098
↑ ratio 10.6 (9 to 12.6) Low relative sit-to-stand power and mobility limitation, women → mobility limitation · Age-adjusted odds ratio, relative STS power below 2.1 W/kg vs above
older women 60-103 y · n = 6,161 · cross sectional · Alcazar J, et al. J Cachexia Sarcopenia Muscle. 2021. PMID 34216098
↑ ratio 1.9 (1.63 to 2.21) Slow chair stand test time and worsening activities of daily living → disability (ADL dependence) · Pooled odds ratio, slow vs normal chair stand test time, longitudinal cohorts
adults >=65 y, longitudinal cohorts (83 articles) · n = 108,428 · meta analysis · Wang DXM, et al. J Cachexia Sarcopenia Muscle. 2020. PMID 31788969

Remedy and magnitude (4)

↑ 1.71 reps (-0.26 to 3.67) Power training, 30-second sit-to-stand · Mean difference in 30s-STS repetitions, power training vs other training or control; TUG MD -0.31 s (-0.63, 0.00)
older adults able to exercise independently, 6 RCTs · n = 217 · meta analysis · Jimenez-Lupion D, et al. Arch Phys Med Rehabil. 2023. PMID 36868491
↓ 1.72 s Resistance plus aerobic/balance exercise, five-repetition chair stand (sarcopenia) · Mean difference in five-repetition chair stand time vs usual care, 1.72 to 2.28 s across resistance+aerobic, resistance+balance and resistance+aerobic+nutrition arms; value is the smaller; MID 2.3 s; no CI reported
12 wk · older adults with sarcopenia, 42 RCTs · n = 3,728 · meta analysis · Shen Y, et al. J Cachexia Sarcopenia Muscle. 2023. PMID 37057640
↑ 2.36 reps (1.5 to 3.21) Tai Chi, 30-second chair stand (sarcopenia/frailty) · Weighted mean difference in 30CST vs control (non-exercise or exercise); sit-to-stand test WMD -2.20 (-2.22 to -2.18) vs non-exercise control
8-48 weeks, 2-7 sessions/week, 30-90 min/session · adults >=60 y with sarcopenia or frailty, 11 RCTs · n = 1,676 · meta analysis · Huang CY, et al. Ageing Res Rev. 2022. PMID 36223875
SMD 0.11 (-0.36 to 0.57) Exercise training (any mode), chair stand time (sarcopenia) · Standardised mean difference in chair stand times vs control, all exercise modes pooled; no change
older people with sarcopenia, 26 studies · n = 1,191 · meta analysis · Lu L, et al. BMC Geriatr. 2021. PMID 34911483

Muscle quality Intramuscular fat / specific force (%; N/cm2) · capacity

2 5 4

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Intermuscular fat area, men with COPD, 0.57 cm2 per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (2)

↑ 0.57 cm2 per year Intermuscular fat area, men with COPD · Per-year increase in L1 intermuscular fat area (11.1% per year)
ages mean 69.7 y · male COPD patients, repeat chest CT · n = 129 · prospective cohort · Wang Y, et al. Front Endocrinol. 2022. PMID 36589831
↓ -2.41 HU per year Trunk muscle CT density, men with COPD · Per-year decrease in L1 trunk muscle density (6.6% per year); mean density 36.4 HU at baseline, mean age 69.7 y
ages mean 69.7 y · male COPD patients, repeat chest CT · n = 129 · prospective cohort · Wang Y, et al. Front Endocrinol. 2022. PMID 36589831

Link to healthspan (5)

↓ ratio 0.69 (0.66 to 0.72) Muscle quality index and all-cause mortality (UK Biobank) → all-cause mortality · Hazard ratio, highest vs lowest sex-specific quintile of MQI (grip strength / arm fat-free mass)
UK Biobank adults · n = 355,209 · prospective cohort · Wang Y, et al. Am J Clin Nutr. 2025. PMID 40930464
↓ ratio 0.69 (0.64 to 0.76) Muscle quality index and incident dementia (UK Biobank) → dementia · Hazard ratio, highest vs lowest quintile of MQI; cardiovascular disease 0.70 (0.68-0.73), type 2 diabetes 0.36 (0.34-0.39)
UK Biobank adults · n = 355,209 · prospective cohort · Wang Y, et al. Am J Clin Nutr. 2025. PMID 40930464
↑ ratio 1.19 (1.05 to 1.35) Intramuscular adipose tissue volume and all-cause mortality (UK Biobank MRI) → all-cause mortality · Adjusted hazard ratio for whole-body MRI intramuscular adipose tissue volume; skeletal muscle fat fraction aHR 1.06 (1.02-1.10)
UK Biobank imaging participants 45-84 y, mean age 65.1 y · n = 36,317 · prospective cohort · Jung M, et al. EBioMedicine. 2024. PMID 39622188
↓ ratio 0.87 (0.78 to 0.97) Thigh muscle density and incident heart failure → heart failure · Hazard ratio per SD of CT thigh muscle density, adjusted for height, weight and cardiovascular risk factors
older adults, 2 cohorts with CT · n = 2,332 · prospective cohort · Zhang L, et al. J Am Heart Assoc. 2022. PMID 34927442
↑ ratio 1.51 (1.28 to 1.79) Quadriceps strength (as muscle quality marker) and mortality, men (Health ABC) → all-cause mortality · Crude hazard ratio per SD (38 Nm) lower isokinetic quadriceps strength; women 1.65 (1.19-2.30); muscle size by CT or DXA not strongly related to mortality
adults 70-79 y, Health ABC · n = 2,292 · prospective cohort · Newman AB, et al. J Gerontol A Biol Sci Med Sci. 2006. PMID 16456196

Remedy and magnitude (4)

↑ 16.7% Whole-body resistance training 2 sessions/week (sarcopenic older women) · Within-group improvement in muscle quality; skeletal muscle mass +4.0%, 1RM strength +20.4%
12 wk · 2 sessions/week, 8 exercises, single set of 10-15 repetitions · sarcopenic older women >60 y · n = 34 · rct · Dos Santos VR, et al. J Strength Cond Res. 2024. PMID 39178393
↑ 13.6% Whole-body resistance training 3 sessions/week (sarcopenic older women) · Within-group improvement in muscle quality; skeletal muscle mass +7.0%, 1RM strength +21.0%
12 wk · 3 sessions/week, 8 exercises, single set of 10-15 repetitions · sarcopenic older women >60 y · n = 34 · rct · Dos Santos VR, et al. J Strength Cond Res. 2024. PMID 39178393
↑ 2.47 kg/kg (1.15 to 3.8) HMB supplementation added to resistance training (sarcopenia) · Difference in change in muscle quality (strength per kg muscle), HMB vs placebo, both with resistance exercise twice weekly
12 wk · HMB twice daily plus resistance exercise twice a week · adults >=60 y with sarcopenia (HMB n = 18, placebo n = 16) · rct · Yang C, et al. J Nutr Health Aging. 2023. PMID 37248756
↑ 0.07 Nm/cm2 (0.03 to 0.11) Resistance training added to caloric restriction plus aerobic training (HFpEF) · Change in leg muscle quality (leg strength / leg skeletal muscle area), RT+CR+AT 0.07 (0.03, 0.11) vs CR+AT 0.02 (-0.02, 0.06), P = 0.04
2 wk · older obese patients with heart failure with preserved ejection fraction · n = 88 · rct · Brubaker PH, et al. Circ Heart Fail. 2023. PMID 36314122

Bone density Areal BMD (hip, spine) (g/cm2) · capacity

4 5 11

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Lumbar spine BMD loss, early postmenopause, -0.022 g/cm2 per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (4)

↓ -0.022 g/cm2 per year Lumbar spine BMD loss, early postmenopause · Average annual loss in the postmenopause (first postmenopausal years)
ages postmenopause · multiethnic women, SWAN · n = 1,902 · prospective cohort · Finkelstein JS, et al. J Clin Endocrinol Metab. 2008. PMID 18160467
↓ -0.018 g/cm2 per year Lumbar spine BMD loss, late perimenopause · Average annual loss during the late perimenopause (little change in pre/early perimenopause)
ages late perimenopause · multiethnic women, SWAN, pre/early perimenopausal at baseline · n = 1,902 · prospective cohort · Finkelstein JS, et al. J Clin Endocrinol Metab. 2008. PMID 18160467
↓ -0.013 g/cm2 per year Total hip BMD loss, early postmenopause · Average annual loss in the postmenopause
ages postmenopause · multiethnic women, SWAN · n = 1,902 · prospective cohort · Finkelstein JS, et al. J Clin Endocrinol Metab. 2008. PMID 18160467
↓ -0.01 g/cm2 per year Total hip BMD loss, late perimenopause · Average annual loss during the late perimenopause
ages late perimenopause · multiethnic women, SWAN · n = 1,902 · prospective cohort · Finkelstein JS, et al. J Clin Endocrinol Metab. 2008. PMID 18160467

Link to healthspan (5)

↓ ratio 0.91 (0.84 to 0.995) Higher femoral neck BMD and incident dementia → dementia · HR for dementia within 10 y per SD increase in baseline BMD (femoral neck DXA or heel eBMD)
adults >=60 y free of dementia (Framingham, Rotterdam, Rush MAP) · n = 4,431 · meta analysis · Lary CW, et al. J Am Geriatr Soc. 2024. PMID 37933827
↑ ratio 1.17 (1.13 to 1.22) Low BMD and all-cause mortality → all-cause mortality · HR per SD decrease in BMD at all sites (meta-analysis of prospective cohorts)
elderly, 10 prospective cohort studies (median follow-up 7 y) · n = 46,182 · meta analysis · Qu X, et al. Int J Cardiol. 2013. PMID 22112679
↑ ratio 1.13 (1.06 to 1.2) Low BMD and cardiovascular mortality → cardiovascular mortality · HR per SD decrease in BMD at all sites
elderly, 10 prospective cohort studies (median follow-up 7 y) · n = 46,182 · meta analysis · Qu X, et al. Int J Cardiol. 2013. PMID 22112679
↑ ratio 1.5 (1.4 to 1.6) Low BMD (any site) and osteoporotic fracture → osteoporotic fracture · Relative risk of fracture per 1 SD decrease in BMD below the age-adjusted mean, all measuring sites
women, 11 prospective cohort populations (~90,000 person-years, >2000 fractures) · meta analysis · Marshall D, et al. BMJ. 1996. PMID 8634613
↑ ratio 2.6 (2 to 3.5) Low hip BMD and hip fracture → hip fracture · Relative risk of hip fracture per 1 SD decrease in hip BMD
women, 11 prospective cohort populations (~90,000 person-years, >2000 fractures) · meta analysis · Marshall D, et al. BMJ. 1996. PMID 8634613

Remedy and magnitude (11)

SMD 0.13 (-0.08 to 0.33) High-intensity vs low-to-moderate-intensity resistance training, femoral neck BMD · Standardised mean difference, >=70% 1RM vs <70% 1RM; lumbar spine 0.28 (-0.02 to 0.58); no between-regimen difference
>=70% 1RM vs <70% 1RM · adults >=50 y, 18 RCTs · n = 1,283 · meta analysis · Shen YC, et al. Geriatr Gerontol Int. 2026. PMID 42366614
↑ SMD 0.41 (0.17 to 0.66) Mind-body exercise (tai chi, yoga, Pilates, qigong, baduanjin) · Standardised mean difference in BMD vs control, perimenopausal and postmenopausal women
perimenopausal and postmenopausal women, 11 RCTs · n = 1,005 · meta analysis · Xu H, et al. Menopause. 2024. PMID 38669625
↑ SMD 0.29 (0.16 to 0.42) Exercise training, lumbar spine BMD (postmenopausal women) · Standardised mean difference vs control, trials of at least 6 months
>=6 months · postmenopausal women, 80 studies · n = 5,581 · meta analysis · Mohebbi R, et al. Osteoporos Int. 2023. PMID 36749350
↑ SMD 0.41 (0.3 to 0.52) Exercise training, total hip BMD (postmenopausal women) · Standardised mean difference vs control, trials of at least 6 months; lumbar spine 0.29 (0.16-0.42), femoral neck 0.27 (0.16-0.39)
>=6 months · postmenopausal women, 80 studies · n = 5,581 · meta analysis · Mohebbi R, et al. Osteoporos Int. 2023. PMID 36749350
↑ 2.77% (0.44 to 5.1) Progressive resistance training, femur/hip BMD (65+) · Mean difference in percent change vs control; favoured by combined resistance plus weight-bearing exercise, lower volumes and higher loads
adults >=65 y, 14 RCTs · meta analysis · O'Bryan SJ, et al. Sports Med. 2022. PMID 35608815
1.6% (-1.44 to 4.63) Progressive resistance training, lumbar spine BMD (65+) · Mean difference in percent change vs control, not significant (p = 0.30)
adults >=65 y, 14 RCTs · meta analysis · O'Bryan SJ, et al. Sports Med. 2022. PMID 35608815
↑ SMD 0.51 (0.28 to 0.74) Dynamic resistance exercise, total hip BMD (postmenopausal women) · Standardised mean difference vs control, trials of at least 6 months; lumbar spine 0.40 (0.15-0.65), femoral neck 0.27 (0.09-0.45)
>=6 months · postmenopausal women, 18 dynamic resistance exercise groups · meta analysis · Kemmler W, et al. Calcif Tissue Int. 2020. PMID 32785775
↑ 3.22% (1.8 to 4.64) Combination exercise programmes, spine BMD · Mean difference in percentage change from baseline vs control
postmenopausal women, 43 RCTs · n = 4,320 · meta analysis · Howe TE, et al. Cochrane Database Syst Rev. 2011. PMID 21735380
↑ 1.03% (0.24 to 1.82) Progressive resistance strength training for the lower limbs, femoral neck BMD · Mean difference in percentage change from baseline vs control (non-weight-bearing high-force exercise)
postmenopausal women, 43 RCTs · n = 4,320 · meta analysis · Howe TE, et al. Cochrane Database Syst Rev. 2011. PMID 21735380
↑ 0.3% High-intensity resistance and impact training (LIFTMOR), femoral neck BMD · Percent change, HiRIT 0.3 +/- 2.6% vs control -1.9 +/- 2.6%, p = 0.004; FN cortical thickness 13.6% vs 6.3%
8 months, twice-weekly 30-min supervised sessions, 5 sets of 5 repetitions at >85% 1RM · postmenopausal women with low bone mass · n = 101 · rct · Watson SL, et al. J Bone Miner Res. 2018. PMID 28975661
↑ 2.9% High-intensity resistance and impact training (LIFTMOR), lumbar spine BMD · Percent change, HiRIT 2.9 +/- 2.8% vs home-based low-intensity control -1.2 +/- 2.8%, p < 0.001
8 months, twice-weekly 30-min supervised sessions, 5 sets of 5 repetitions at >85% 1RM · postmenopausal women with low bone mass, aged 65 +/- 5 y · n = 101 · rct · Watson SL, et al. J Bone Miner Res. 2018. PMID 28975661

Flexibility Sit-and-reach / joint range of motion (cm; degrees) · capacity

4 4 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (4)

↓ -32% Cervical extension range of motion, elderly vs young · Mean cervical extension approximately 32% less in adults 70-90 y than 20-30 y (p < .001), gravity goniometer
ages 70-90 y vs 20-30 y · 42 adults 70-90 y vs 31 adults 20-30 y · cross sectional · Kuhlman KA. Arch Phys Med Rehabil. 1993. PMID 8215859
↓ -12% Cervical flexion range of motion, elderly vs young · Mean cervical flexion approximately 12% less in adults 70-90 y than 20-30 y (p < .001)
ages 70-90 y vs 20-30 y · 42 adults 70-90 y vs 31 adults 20-30 y · cross sectional · Kuhlman KA. Arch Phys Med Rehabil. 1993. PMID 8215859
↓ -22% Cervical lateral flexion range of motion, elderly vs young · Mean cervical lateral flexion approximately 22% less in adults 70-90 y than 20-30 y (p < .001)
ages 70-90 y vs 20-30 y · 42 adults 70-90 y vs 31 adults 20-30 y · cross sectional · Kuhlman KA. Arch Phys Med Rehabil. 1993. PMID 8215859
↓ -25% Cervical rotation range of motion, elderly vs young · Mean cervical rotation approximately 25% less in adults 70-90 y than 20-30 y (p < .001)
ages 70-90 y vs 20-30 y · 42 adults 70-90 y vs 31 adults 20-30 y · cross sectional · Kuhlman KA. Arch Phys Med Rehabil. 1993. PMID 8215859

Link to healthspan (4)

↓ ratio 0.79 (0.67 to 0.93) Chair sit-and-reach and mortality in older adults → all-cause mortality · Adjusted HR, highest vs lowest performance quintile of the chair sit-and-reach test
community-dwelling adults >=65 y, Taiwan, median follow-up 7.0 y · n = 13,423 · prospective cohort · Wu MC, et al. JAMA Netw Open. 2026. PMID 42574013
↑ ratio 1.29 (1.19 to 1.38) Bilateral upper-limb flexibility impairment and mortality, oldest-old → all-cause mortality · Adjusted HR for impairment of both left and right upper-limb flexibility (neck, lower back, arms raised) vs none
oldest-old >=80 y, Chinese Longitudinal Healthy Longevity Survey · n = 21,861 · prospective cohort · Zhang Y, et al. J Glob Health. 2025. PMID 41039874
↑ ratio 1.87 (1.5 to 2.33) Low body flexibility (Flexindex) and mortality, men → all-cause mortality · Adjusted HR comparing the upper and bottom of the Flexindex distribution (20 movements, 7 joints, score 0-80)
adults aged 46-65 y (66% men), mean follow-up 12.9 y · n = 3,139 · prospective cohort · Araujo CGS, et al. Scand J Med Sci Sports. 2024. PMID 39165228
↑ ratio 4.78 (1.23 to 31.71) Low body flexibility (Flexindex) and mortality, women → all-cause mortality · Adjusted HR comparing the upper and bottom of the Flexindex distribution
adults aged 46-65 y (66% men), mean follow-up 12.9 y · n = 3,139 · prospective cohort · Araujo CGS, et al. Scand J Med Sci Sports. 2024. PMID 39165228

Remedy and magnitude (3)

↑ SMD 1.042 Resistance training in untrained or sedentary people (range of motion) · Effect size for range of motion in untrained/sedentary participants; trained or active people ES 0.43
untrained and sedentary healthy participants · meta analysis · Alizadeh S, et al. Sports Med. 2023. PMID 36622555
↑ SMD 0.73 Resistance training vs control (range of motion) · Effect size for joint range of motion, chronic resistance training vs control; no improvement with body-mass-only resistance training
external-load resistance training; no effect of age, duration or frequency in meta-regression · healthy participants, 55 studies · meta analysis · Alizadeh S, et al. Sports Med. 2023. PMID 36622555
SMD 0.08 Resistance training vs stretch training (range of motion) · Effect size, resistance training vs stretch training; resistance+stretch vs stretch alone ES -0.001 (p = 0.99)
healthy participants, 55 studies · meta analysis · Alizadeh S, et al. Sports Med. 2023. PMID 36622555

Trabecular bone quality Trabecular bone score / HR-pQCT microarchitecture (TBS; mm) · physical parameter

2 3 2

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: TBS decline after the final menstrual period, -0.89% per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (2)

↓ -0.89% per year TBS decline after the final menstrual period · Annual rate of TBS loss starting 2 years after the final menstrual period
ages postmenopause · midlife women (SWAN) · prospective cohort · Greendale GA, et al. J Clin Endocrinol Metab. 2020 PMID 31613958
↓ -1.16% per year TBS decline during the menopause transition · Annual TBS loss beginning 1.5 years before the final menstrual period
ages menopause transition · midlife women (SWAN) · prospective cohort · Greendale GA, et al. J Clin Endocrinol Metab. 2020 PMID 31613958

Link to healthspan (3)

↑ ratio 1.38 (1.04 to 1.84) Lumbar spine TBS and major osteoporotic fracture in older men → major osteoporotic fracture · HR per SD decrease in TBS, analysed jointly with bone strain index
men aged 60 or over, 12-year follow-up · n = 825 · prospective cohort · Blanc Q, et al. Eur J Endocrinol. 2024 PMID 39607895
↑ ratio 1.36 (1.3 to 1.42) Lumbar spine TBS and major osteoporotic fracture → major osteoporotic fracture · HR per SD reduction in TBS, unadjusted
women aged 40-100 · n = 33,352 · prospective cohort · Leslie WD, et al. Osteoporos Int. 2014 PMID 24951032
↑ ratio 1.32 (1.26 to 1.39) Lumbar spine TBS and mortality → mortality · HR per SD reduction in TBS, unadjusted
women aged 40-100 · n = 33,352 · prospective cohort · Leslie WD, et al. Osteoporos Int. 2014 PMID 24951032

Remedy and magnitude (2)

↑ 4.4% Abaloparatide then alendronate, cumulative TBS at 43 months · Abaloparatide 18 months then alendronate 24 months; placebo/alendronate cumulative increase 1.7%
abaloparatide 18 months then alendronate 24 months · postmenopausal women with osteoporosis · n = 911 · rct · Cosman F, et al. J Bone Miner Res. 2023 PMID 36588166
↑ 4% Abaloparatide, TBS at 18 months · Abaloparatide vs placebo for 18 months (ACTIVE); mean TBS (thickness-adjusted) change; unchanged with placebo
18 months · postmenopausal women with osteoporosis · n = 911 · rct · Cosman F, et al. J Bone Miner Res. 2023 PMID 36588166

Muscle and nerve physiology

Type II fibre size Type II muscle fibre cross-sectional area (biopsy) (um2) · physical parameter

1 1 7

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↓ r = -0.56 Type II fibre size vs age across adulthood · Type II fibre size smaller with increasing age in adults, vastus lateralis biopsies (18-86 yr); type I fibres not affected
ages 18-86 yr · healthy children and adults 18-86 yr · n = 165 · cross sectional · Verdijk LB, et al. Age. 2014 PMID 24122288

Link to healthspan (1)

↑ r = 0.63 Type II fibre area and functional recovery after hip-fracture arthroplasty → physical function recovery (SPPB) · Correlation of vastus lateralis type II average fibre area with SPPB 2 weeks after THA
patients undergoing THA for femoral neck fracture (vastus lateralis biopsy at surgery) · n = 34 · prospective cohort · Song SK, et al. Acta Orthop. 2024. PMID 39466193

Remedy and magnitude (7)

↑ 6.5% Endurance training, fibre CSA · Low/moderate-intensity continuous endurance training; muscle fibre CSA change
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310
↑ 11.9% Sprint interval training, fibre CSA · Sprint interval training; muscle fibre CSA change
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310
↓ SMD -0.13 (-0.39 to 0.12) Concurrent aerobic plus strength vs strength training alone · Type II fibre hypertrophy, concurrent training vs identical strength training without aerobic training (at least 4 weeks)
healthy adults · meta analysis · Lundberg TR, et al. Sports Med. 2022 PMID 35476184
↑ SMD 1.44 (0.93 to 1.95) Resistance vs aerobic training, type II fibre CSA · Pooled Hedges g, resistance training vs aerobic training, type II fibre CSA
healthy adults, knee extensor · meta analysis · Grgic J, et al. Sports Med. 2019 PMID 30341595
↑ 310 um2 (51 to 570) Protein supplementation during resistance training · Protein supplementation vs placebo during resistance exercise training of at least 6 weeks; muscle fibre CSA
healthy adults · n = 1,863 · meta analysis · Morton RW, et al. Br J Sports Med. 2018 PMID 28698222
↑ 17% Resistance training with active recovery, healthy men · 12-wk strength training 2 days/wk with active recovery after sessions; type II fibre CSA
12 wk · 2 days/week, active recovery · physically active young men · n = 21 · rct · Roberts LA, et al. J Physiol. 2015 PMID 26174323
↑ 20.1% Resistance training in older women · 12-wk resistance training (seven lower-extremity exercises) vs non-exercising control; type II fibre CSA
12 wk · seven exercises stressing lower-extremity muscle groups · healthy women, mean age 69 yr · n = 19 · rct · Charette SL, et al. J Appl Physiol. 1991 PMID 1864770

Type I fibre size Type I muscle fibre cross-sectional area (biopsy) (um2) · physical parameter

0 1 2

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (0)

no quantified finding yet

Link to healthspan (1)

r = 0.12 Type I fibre area and functional recovery after hip-fracture arthroplasty → physical function recovery (SPPB) · Partial correlation of vastus lateralis type I average fibre area with SPPB 2 weeks after THA
patients undergoing THA for femoral neck fracture (vastus lateralis biopsy at surgery) · n = 34 · prospective cohort · Song SK, et al. Acta Orthop. 2024. PMID 39466193

Remedy and magnitude (2)

↑ SMD 0.99 (0.44 to 1.54) Resistance vs aerobic training, type I fibre CSA · Pooled Hedges g, resistance training vs aerobic training, type I fibre CSA
healthy adults, knee extensor · meta analysis · Grgic J, et al. Sports Med. 2019 PMID 30341595
↑ 9.5% Progressive resistance training in older women with heart failure · 10-wk progressive resistance training vs stretching control; type I fibre area
1 wk · progressive resistance training · older women with chronic heart failure · n = 16 · rct · Pu CT, et al. J Appl Physiol. 2001 PMID 11356801

Motor unit number Motor unit number estimate / firing rate (units; Hz) · physical parameter

4 0 2

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (4)

↓ SMD -0.65 (-0.96 to -0.34) Motor unit discharge rate at high force, older vs younger · SMD of discharge rate, older vs younger adults, contractions above 60% MVC
ages older vs younger adults · older vs younger adults · meta analysis · Adugna DG, et al. Neurobiol Aging. 2026 PMID 42520337
↓ SMD -0.34 (-0.5 to -0.18) Motor unit discharge rate at low force, older vs younger · SMD of discharge rate, older vs younger adults, contractions below 30% MVC
ages older vs younger adults · older vs younger adults · meta analysis · Adugna DG, et al. Neurobiol Aging. 2026 PMID 42520337
↑ SMD 0.44 (0.15 to 0.72) Motor unit discharge rate variability, older vs younger · SMD of discharge rate variability, older vs younger adults (greater in older)
ages older vs younger adults · older vs younger adults · meta analysis · Adugna DG, et al. Neurobiol Aging. 2026 PMID 42520337
↓ SMD 0.66 (0.29 to 1.04) Motor unit discharge rate, young vs older adults · Pooled SMD, motor unit discharge rate higher in younger than older adults (29 studies)
ages young vs older adults · young vs older adults · meta analysis · Orssatto LBR, et al. Mech Ageing Dev. 2022 PMID 35218849

Link to healthspan (0)

no quantified finding yet

Remedy and magnitude (2)

↑ 11.3% Isometric strength training, discharge rate at constant force (older adults) · 4-week supervised isometric dorsiflexor strength training vs habitual-activity control; tibialis anterior motor units tracked longitudinally
4 wk · supervised isometric strength training · untrained older adults (~70 y), tibialis anterior HD-sEMG · n = 23 · rct · Casolo A, et al. J Physiol. 2026. PMID 41823343
↑ 8.2% Isometric strength training, discharge rate at recruitment (older adults) · 4-week supervised isometric dorsiflexor strength training vs control
4 wk · supervised isometric strength training · untrained older adults (~70 y), tibialis anterior HD-sEMG · n = 23 · rct · Casolo A, et al. J Physiol. 2026. PMID 41823343

Muscle cross-sectional area Quadriceps anatomical cross-sectional area / muscle thickness (cm2; mm) · physical parameter

4 1 7

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Mid-thigh muscle CSA decline with age, men, -0.6% per year.

Change with age (4)

↓ -30% Quadriceps volume, older vs young men · Quadriceps femoris muscle volume (MRI) 30% lower in older (1.6 L) than young (2.3 L) men
ages 27 +/- 4 y vs 71 +/- 6 y · healthy young (27 y) and older (71 y) men, MRI · n = 20 · cross sectional · Fuchs CJ, et al. Exp Gerontol. 2023. PMID 36967049
↓ -0.6% per year Mid-thigh muscle CSA decline with age, men · Thigh muscle cross-sectional area (CT) decreased 0.6%/year across age 40-89; quadriceps CSA accounted for 65.6% of the decrease
ages 40-89 y · randomly selected Japanese residents aged 40-89 y (mid-thigh CT) · n = 2,310 · cross sectional · Kasai T, et al. Geriatr Gerontol Int. 2015. PMID 25244543
↓ -0.4% per year Mid-thigh muscle CSA decline with age, women · Thigh muscle cross-sectional area (CT) decreased 0.4%/year; quadriceps CSA accounted for 81.6% of the decrease
ages 40-89 y · randomly selected Japanese residents aged 40-89 y (mid-thigh CT) · n = 2,310 · cross sectional · Kasai T, et al. Geriatr Gerontol Int. 2015. PMID 25244543
↓ -16.1% Quadriceps CSA over 12 years (longitudinal) · Quadriceps femoris CSA (CT) reduced by 16.1% between 1985-86 and 1997-98
ages 65.4 y at baseline, 12-y follow-up · healthy sedentary men, initial mean age 65.4 y, CT in 7 · n = 9 · prospective cohort · Frontera WR, et al. J Appl Physiol. 2000. PMID 10749826

Link to healthspan (1)

↓ ratio 16.6 (2 to 136) Ultrasound quadriceps thickness sarcopenia and acute decompensation → acute decompensation (liver disease) · US-defined sarcopenia (quadriceps thickness standardised per height, cut-off 1.83 cm/m) vs none; risk of acute decompensation within 1 year
chronic liver disease with portal hypertension · n = 63 · prospective cohort · Godiker J, et al. J Cachexia Sarcopenia Muscle. 2024 PMID 39529225

Remedy and magnitude (7)

↑ 0.11 cm (0.06 to 0.16) Electrotherapy after stroke, muscle thickness · Electrotherapy vs conventional therapy; lower limb muscle thickness
people after stroke · meta analysis · Debeuf R, et al. Disabil Rehabil. 2025 PMID 38557249
↑ SMD 0.11 (-0.02 to 0.25) Creatine plus resistance training, muscle hypertrophy · Creatine supplementation plus resistance training vs placebo plus resistance training; standardised direct imaging measures of regional hypertrophy
healthy adults · meta analysis · Burke R, et al. Nutrients. 2023 PMID 37432300
↑ SMD 0.88 Full vs partial range of motion training, lower-limb hypertrophy · Resistance training with full vs partial range of motion; lower-limb hypertrophy
healthy adults · meta analysis · Pallares JG, et al. Scand J Med Sci Sports. 2021 PMID 34170576
↑ 5.8% Blood flow restriction training after ACL reconstruction, muscle thickness · 8-wk BFR resistance training at 30% 1RM, biweekly leg press; vastus lateralis muscle thickness
8 wk · 30% 1RM with blood flow restriction, twice weekly · ACL reconstruction patients · n = 24 · rct · Hughes L, et al. Sports Med. 2019 PMID 31301034
↑ 6.7% Heavy-load training after ACL reconstruction, muscle thickness · 8-wk heavy-load resistance training at 70% 1RM, biweekly leg press; vastus lateralis muscle thickness
8 wk · 70% 1RM, twice weekly · ACL reconstruction patients · n = 24 · rct · Hughes L, et al. Sports Med. 2019 PMID 31301034
↑ 19.5% Heavy resistance training (80% 1RM), vastus lateralis CSA · 12-wk resistance training, 80% 1RM volume-matched condition; vastus lateralis CSA
12 wk · twice a week, 80% 1RM · men · n = 30 · rct · Lasevicius T, et al. Eur J Sport Sci. 2018 PMID 29564973
↑ 8.9% Light-load resistance training (20% 1RM), vastus lateralis CSA · 12-wk resistance training, 20% 1RM volume-matched condition; vastus lateralis CSA
12 wk · twice a week, 20% 1RM · men · n = 30 · rct · Lasevicius T, et al. Eur J Sport Sci. 2018 PMID 29564973

Muscle oxidative capacity 31P-MRS phosphocreatine recovery / mitochondrial respiration (s; pmol/s/mg) · physical parameter

1 2 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↑ r = 0.55 Phosphocreatine recovery time vs age · 31P-MRS PCr recovery after submaximal exercise lengthens with age (8-55 yr); prolonged recovery = lower oxidative capacity
ages 8-55 yr · healthy children and adults 8-55 yr · n = 121 · cross sectional · Fleischman A, et al. J Clin Endocrinol Metab. 2010 PMID 20554709

Link to healthspan (2)

↑ ratio 1.32 (1.13 to 1.54) Lower muscle mitochondrial respiration and multimorbidity → multimorbidity · Proportional OR for a higher multimorbidity index per SD decrement in maximal OXPHOS (CI+CII) of permeabilised fibres
older adults, Study of Muscle, Mobility and Aging (mean age 76.4 y), respirometry of biopsies · n = 764 · cross sectional · Mau T, et al. J Gerontol A Biol Sci Med Sci. 2024. PMID 38605684
↓ ratio 0.483 (0.24 to 0.972) Muscle oxidative capacity (kPCr) and incident MCI/dementia → mild cognitive impairment or dementia · HR per SD higher post-exercise PCr recovery rate (kPCr, 31P-MRS)
cognitively normal older adults, Baltimore Longitudinal Study of Aging (31P-MRS kPCr) · n = 469 · prospective cohort · Tian Q, et al. Alzheimers Dement. 2023. PMID 37530130

Remedy and magnitude (3)

↑ 23% Endurance training, mitochondrial content · Low/moderate-intensity continuous endurance training; skeletal muscle mitochondrial content
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310
↑ 27% High-intensity interval training, mitochondrial content · High-intensity interval or continuous training; skeletal muscle mitochondrial content
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310
↑ 27% Sprint interval training, mitochondrial content · Sprint interval training; skeletal muscle mitochondrial content
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310

Capillary density Capillaries per fibre / capillary density (biopsy) (capillaries/fibre) · physical parameter

1 0 6

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↓ r = -0.299 Capillary density vs age in male master cyclists · Vastus lateralis capillary density correlated with age in males aged 55-79
ages 55-79 yr · highly active master cyclists aged 55-79 · n = 90 · cross sectional · Pollock RD, et al. Aging Cell. 2018 PMID 29517834

Link to healthspan (0)

no quantified finding yet

Remedy and magnitude (6)

↑ 15% Endurance training, capillaries per fibre · Low/moderate-intensity continuous endurance training; capillaries per fibre
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310
↑ 13% High-intensity interval training, capillaries per fibre · High-intensity interval or continuous training; capillaries per fibre
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310
↑ 10% Sprint interval training, capillaries per fibre · Sprint interval training; capillaries per fibre
healthy and clinical adults · n = 5,973 · meta analysis · Molmen KS, et al. Sports Med. 2025 PMID 39390310
↑ SMD 0.4 (0.1 to 0.7) Hypoxic vs normoxic exercise training, capillarization · Exercise training in hypoxia vs normoxia; skeletal muscle capillarization
adults, mean age 19-57 yr · n = 182 · meta analysis · Montero D, et al. Sports Med. 2016 PMID 27286988
↑ 8.4% Endurance training in Huntington disease, capillary-to-fibre ratio · 26-wk endurance training; overall capillary-to-fibre ratio
26 wk · endurance training · Huntington disease patients · n = 13 · rct · Mueller SM, et al. Orphanet J Rare Dis. 2017 PMID 29258585
↑ 6.4% Endurance training in healthy controls, capillary-to-fibre ratio · 26-wk endurance training; overall capillary-to-fibre ratio
26 wk · endurance training · healthy controls · n = 11 · rct · Mueller SM, et al. Orphanet J Rare Dis. 2017 PMID 29258585

Voluntary activation Central activation ratio / voluntary activation (%) · physical parameter

2 0 1

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↓ -13% Calf activation capacity, older vs younger · Plantar-flexor activation capacity (twitch superimposition) decreased with age by 13%
ages 24 +/- 1 y vs 68 +/- 1 y · healthy younger (24 y), middle-aged (46 y) and older (68 y) subjects · n = 70 · cross sectional · Onambele GL, et al. J Appl Physiol. 2006. PMID 16455811
↓ SMD -0.45 (-0.62 to -0.29) Voluntary activation, old vs young (meta-analysis) · Lower voluntary activation during maximal isometric contractions in old vs young adults (Cohen d)
ages 18-35 y vs >60 y · young (18-35 y) vs old (>60 y) adults, 54 studies, ITT or CAR · meta analysis · Rozand V, et al. Med Sci Sports Exerc. 2020. PMID 31688647

Link to healthspan (0)

no quantified finding yet

Remedy and magnitude (1)

↑ 3% Short-term dexamethasone · Dexamethasone 8 mg/d vs placebo for 7 d; voluntary activation by interpolated twitch with TMS, ankle dorsiflexors
8 mg/d for 7 d · healthy young men · n = 17 · rct · mechanism: decreased excitability of intracortical inhibitory circuits · Baudry S, et al. Med Sci Sports Exerc. 2018 PMID 28930864

Rate of force development Isometric rate of force development (N/s) · physical parameter

2 1 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↓ -43% Knee-extensor RFD 0-100 ms, old vs young males · Voluntary rate of force development ~43% lower in old (70 y) than young (26 y) males (0-200 ms: ~40% lower)
ages 26.4 +/- 1.5 y vs 70.1 +/- 2.8 y · healthy young (26 y) and old (70 y) males, knee extensors · n = 16 · cross sectional · Dalton BE, et al. Eur J Appl Physiol. 2023. PMID 36484861
↓ -39% Knee-extensor RFD, old vs young males · Contractile RFD and impulse ~39% lower in old than young recreationally active men before disuse
ages 24.3 y vs 67.2 y · recreationally active healthy young (24 y) and old (67 y) males, knee extensors · n = 22 · cross sectional · Hvid LG, et al. Exp Gerontol. 2014. PMID 24447828

Link to healthspan (1)

↓ ratio 0.68 (0.51 to 0.92) Fastest vs slowest quadriceps RFD tertile and worsening of self-reported physical function → worsening self-reported physical function (WOMAC) · OR for worsening WOMAC physical function over 36 months, fastest vs slowest RFD tertile, adjusted for age, sex, BMI, depression, chronic disease, knee pain
adults with or at risk for knee osteoarthritis (Osteoarthritis Initiative) · n = 2,630 · prospective cohort · Hu B, et al. Arch Phys Med Rehabil. 2018 PMID 29408538

Remedy and magnitude (3)

↓ SMD -0.28 (-0.48 to -0.08) Concurrent aerobic plus strength vs strength training alone: explosive strength · Pooled SMD for explosive strength (concurrent minus strength alone); negative = attenuation
healthy adults · meta analysis · Schumann M, et al. Sports Med. 2022 PMID 34757594
↑ 38.9% Hypertrophy training (bench press) · RFD at 50% of 1RM, HT (3x8-12 at ~70-80% 1RM) vs control; 3 sessions/week
8 wk · 3 sessions/week, 3x8-12 reps at ~70%-80% 1RM · moderately trained adults · n = 63 · rct · Trane G, et al. Med Sci Sports Exerc. 2025 PMID 39679645
↑ 58.4% Maximal strength training (bench press) · RFD at 50% of 1RM, MST (4x4 at >=85% 1RM) vs control; 3 sessions/week
8 wk · 3 sessions/week, 4x4 reps at >=85% 1RM · moderately trained adults · n = 63 · rct · Trane G, et al. Med Sci Sports Exerc. 2025 PMID 39679645

Tendon stiffness Tendon stiffness / Young modulus (N/mm; GPa) · physical parameter

2 1 5

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↓ -44% Achilles tendon stiffness at matched activation, older vs younger · Achilles tendon stiffness 44% lower in older adults at matched triceps surae activations
ages 23 +/- 4 y vs 72 +/- 5 y · younger (23 y) and older (72 y) adults · n = 30 · cross sectional · Gray AJ, et al. J Appl Physiol. 2024. PMID 39508895
↓ -43% Achilles tendon stiffness, older vs younger active adults · Achilles tendon stiffness 43% lower in older than younger physically active adults
ages 21 +/- 3.25 y vs 69 +/- 2.86 y · physically active younger (21 y) and older (69 y) adults · cross sectional · Lindemann I, et al. J Biomech. 2020. PMID 33035839

Link to healthspan (1)

↓ ratio 0.982 (0.965 to 0.999) Achilles tendon shear-wave stiffness and frailty → frailty · Adjusted OR for Fried frailty per unit of Achilles tendon shear-wave elastography (kPa)
outpatients aged >=65 y (mean 73.8 y), Achilles shear-wave elastography · n = 148 · cross sectional · Ceker E, et al. Eur Geriatr Med. 2024. PMID 39090315

Remedy and magnitude (5)

↑ SMD 1.04 (0.65 to 1.43) High-strain vs low-strain resistance training, tendon stiffness · Higher localised tendon strain protocols: stiffness SMD
healthy adults (61 studies) · n = 763 · meta analysis · Lazarczuk SL, et al. Sports Med. 2022 PMID 35657492
↑ SMD 0.74 (0.62 to 0.86) Mechanical loading (mostly resistance training), tendon stiffness · Pooled effect of loading on lower-limb tendon stiffness
healthy adults (61 studies) · n = 763 · meta analysis · Lazarczuk SL, et al. Sports Med. 2022 PMID 35657492
↑ SMD 0.378 Collagen peptide supplementation, Achilles tendon stiffness · 10 g/day collagen peptide vs placebo; shear wave elastography; Cohen's d within the CP group
16 wk · 10 g/day · healthy young sedentary men · n = 50 · rct · Miyamoto N, et al. Med Sci Sports Exerc. 2025 PMID 40623147
↑ 39.1% Heavy strength training in triathletes: Achilles tendon · Strength training 3x/week added to endurance training vs endurance-only
12 wk · 3 sessions/week · well-trained triathletes · n = 18 · rct · Jacobs MW, et al. Sci Rep. 2025 PMID 40717194
↑ 15.8% Heavy strength training in triathletes: patellar tendon · Strength training 3x/week added to endurance training vs endurance-only
12 wk · 3 sessions/week · well-trained triathletes · n = 18 · rct · Jacobs MW, et al. Sci Rep. 2025 PMID 40717194

Knee-extensor torque Isometric/isokinetic knee-extensor torque (N*m) · physical parameter

2 4 5

Trajectory with age: default, and given an intervention

Intervention starts at age 65

Default (no intervention)Given the selected intervention

Default: Isometric knee extensor strength across ages 65-89, 1% per year (1 to 2).

Change with age (2)

↓ -34% Knee extensor strength, older vs younger adults · Knee extensor strength lower in the two older cohorts (61 y and 72 y) than in 25 y and 37 y cohorts
ages mean 61 and 72 y vs 25 and 37 y · untrained healthy men and women · n = 221 · cross sectional · Roberts BM, et al. Exp Gerontol. 2018 PMID 29481967
↓ 1% per year (1 to 2) Isometric knee extensor strength across ages 65-89 · Difference over the age range 65-89 y equivalent to 1-2% loss per annum (value shown is the lower bound of the stated range)
ages 65-89 y · healthy community-dwelling older men and women · n = 100 · cross sectional · Skelton DA, et al. Age Ageing. 1994 PMID 7825481

Link to healthspan (4)

↑ ratio 1.55 (1.17 to 2.06) Low quadriceps isometric strength and mortality in heart failure → mortality · Low QIS (< 36.2% body mass) vs not low, adjusted for HF risk score
older patients with heart failure · n = 1,273 · prospective cohort · Nakamura T, et al. Can J Cardiol. 2021 PMID 32622879
↑ ratio 1.77 (1.41 to 2.23) Knee extension strength cutpoints and mortality → mortality · High-risk category (<1.13 Nm/kg men, <1.01 Nm/kg women) vs low-risk category (>1.71 and >1.34 Nm/kg)
initially well-functioning adults aged ~73.6 · prospective cohort · Manini TM, et al. J Am Geriatr Soc. 2007 PMID 17341251
↑ ratio 1.51 (1.28 to 1.79) Quadriceps strength and mortality (men) → mortality · Crude HR per SD (38 Nm) lower quadriceps strength, men, isokinetic dynamometry
community-dwelling adults aged 70-79 · n = 2,292 · prospective cohort · Newman AB, et al. J Gerontol A Biol Sci Med Sci. 2006 PMID 16456196
↑ ratio 1.65 (1.19 to 2.3) Quadriceps strength and mortality (women) → mortality · Crude HR per SD (38 Nm) lower quadriceps strength, women, isokinetic dynamometry
community-dwelling adults aged 70-79 · n = 2,292 · prospective cohort · Newman AB, et al. J Gerontol A Biol Sci Med Sci. 2006 PMID 16456196

Remedy and magnitude (5)

↑ SMD 0.73 (0.29 to 1.16) NMES added to physiotherapy after ACL surgery · Neuromuscular electrical stimulation plus standard physical therapy vs physical therapy alone, quadriceps strength
NMES, 4-12 weeks after surgery · patients after anterior cruciate ligament surgery (6 RCTs pooled) · meta analysis · Hauger AV, et al. Knee Surg Sports Traumatol Arthrosc. 2018. PMID 28819679
↑ 18.4 Nm (10.1 to 26.6) Heavy resistance training + whey, dynamic strength · Heavy resistance training 3x/week with whey vs whey alone, dynamic knee extensor strength
52 wk · heavy resistance training 3x/week + 20 g whey protein twice daily · healthy older adults >65 y · n = 208 · rct · Mertz KH, et al. Am J Clin Nutr. 2021. PMID 33564844
↑ 23.9 Nm (14.2 to 33.6) Heavy resistance training + whey, isometric strength · Heavy resistance training 3x/week with whey vs whey alone, between-group difference in isometric knee extensor strength
52 wk · heavy resistance training 3x/week + 20 g whey protein twice daily · healthy older adults >65 y · n = 208 · rct · Mertz KH, et al. Am J Clin Nutr. 2021. PMID 33564844
↑ 13.7 Nm (5.3 to 22.1) Light-intensity resistance training + whey, dynamic strength · Light-intensity resistance training 3-5x/week with whey vs whey alone, dynamic knee extensor strength
52 wk · light-intensity resistance training 3-5x/week + whey · healthy older adults >65 y · n = 208 · rct · Mertz KH, et al. Am J Clin Nutr. 2021. PMID 33564844
↑ 31% Eccentric cross-education after ACL reconstruction · 8 weeks of eccentric isokinetic training of the uninjured knee (60 deg/s, 3 d/week) added to rehabilitation vs rehabilitation alone; quadriceps MVIC
8 wk · isokinetic eccentric training of contralateral knee, 3 days/week · patients 4 weeks after ACL reconstruction (mean age 29.5 y) · n = 48 · rct · Harput G, et al. Knee Surg Sports Traumatol Arthrosc. 2019. PMID 29959448

Nerve conduction velocity Motor/sensory nerve conduction velocity (m/s) · physical parameter

2 2 2

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Median sensory nerve conduction velocity, longitudinal, -0.41 m/s per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (2)

↓ -0.41 m/s per year Median sensory nerve conduction velocity, longitudinal · Rate of change, controlling for gender, age, hand temperature and BMI
adult attendees of annual meetings (two or more observations) · n = 704 · prospective cohort · Werner RA, et al. Muscle Nerve. 2012 PMID 22190308
↓ -0.29 m/s per year Ulnar sensory nerve conduction velocity, longitudinal · Rate of change, controlling for gender, age, hand temperature and BMI
adult attendees of annual meetings (two or more observations) · n = 704 · prospective cohort · Werner RA, et al. Muscle Nerve. 2012 PMID 22190308

Link to healthspan (2)

↑ ratio 1.18 (0.91 to 1.54) Slow peroneal conduction velocity and incident dementia (Health ABC) → dementia · Slow conduction velocity (impairment) borderline associated with dementia after covariate adjustment
Black and White adults 70-79 y without dementia, Health ABC · n = 2,174 · prospective cohort · Brenowitz WD, et al. Neurology. 2022. PMID 35264428
ratio 1.06 (0.95 to 1.19) Lower peroneal motor NCV and incident mobility disability (Health ABC) → incident mobility disability · HR per SD lower motor nerve conduction velocity, fully adjusted model (model 4); minimally adjusted 1.10 (0.99-1.22)
community-dwelling older adults, Health ABC · n = 2,148 · prospective cohort · Ward RE, et al. J Am Geriatr Soc. 2014. PMID 25482096

Remedy and magnitude (2)

↑ 2.1 m/s (0.35 to 3.86) Vitamin B supplementation: sural nerve conduction velocity · 13 RCTs, vitamin B (any form) vs placebo or standard care; sural NCV MD 2.10 m/s
adults with diabetic peripheral neuropathy · n = 834 · meta analysis · Mandra EV, et al. J Clin Med. 2026. PMID 42452619
↓ -1.23 m/s (-2.37 to -0.09) Vitamin B supplementation: tibial nerve conduction velocity · Tibial velocity favoured control: MD -1.23 m/s
adults with diabetic peripheral neuropathy · n = 834 · meta analysis · Mandra EV, et al. J Clin Med. 2026. PMID 42452619

Cardiorespiratory

Aerobic capacity VO2max (mL/kg/min) · capacity on the landscape

2 6 16

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, NHANES adults, 1999-2004 (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (2)

↓ -7 mL/kg/min Median, ages 40–59 vs 20–39 catalogue · 42 → 35 (-17%)
ages 40–59 vs 20–39 · NHANES adults, 1999-2004 · n = 3,500 · cross sectional · National Center for Health Statistics. National Health and Nutrition Examination Survey: 2017-2018 laboratory data. Hyattsville, MD: Centers for Disease Control and Prevention; 2020. doi 10.15620/cdc:106318
↓ -13.5 mL/kg/min Median, ages 60+ vs 20–39 catalogue · 42 → 28.5 (-32%)
ages 60+ vs 20–39 · NHANES adults, 1999-2004 · n = 2,800 · cross sectional · National Center for Health Statistics. National Health and Nutrition Examination Survey: 2017-2018 laboratory data. Hyattsville, MD: Centers for Disease Control and Prevention; 2020. doi 10.15620/cdc:106318

Link to healthspan (6)

↑ ratio 1.92 (1.43 to 2.57) All-cause mortality, normal weight-unfit vs normal weight-fit → all-cause mortality · Pooled HR, reference normal weight-fit; CRF from maximal or VO2peak exercise test
adults, 20 prospective cohorts · n = 398,716 · meta analysis · Weeldreyer NR, et al. Br J Sports Med. 2025. PMID 39537313
↑ ratio 0.87 (0.84 to 0.9) All-cause mortality per 1 MET higher fitness → all-cause mortality · Pooled RR per 1-MET higher maximal aerobic capacity (corresponding to 1 km/h higher running speed); healthy men and women
healthy adults, 33 cohort studies · n = 102,980 · meta analysis · Kodama S, et al. JAMA. 2009. PMID 19454641
↑ ratio 1.7 (1.51 to 1.92) All-cause mortality, low vs high fitness → all-cause mortality · RR for low CRF (<7.9 METs) vs high CRF (>=10.9 METs)
healthy adults, 33 cohort studies · n = 102,980 · meta analysis · Kodama S, et al. JAMA. 2009. PMID 19454641
↑ ratio 5.04 (4.1 to 6.2) All-cause mortality, low vs elite fitness → all-cause mortality · Adjusted HR for low (<25th percentile) vs elite (>=97.7th percentile) age- and sex-matched CRF on treadmill testing
adults referred for exercise treadmill testing, mean age 53.4 · n = 122,007 · prospective cohort · Mandsager K, et al. JAMA Netw Open. 2018. PMID 30646252
↑ ratio 0.47 (0.39 to 0.56) All-cause mortality, high vs low fitness (overview of meta-analyses) → all-cause mortality · HR high vs low CRF, general populations; 199 cohort studies, >20.9 million observations
adults, general populations · systematic review · Lang JJ, et al. Br J Sports Med. 2024. PMID 38599681
ratio 0.49 (0.42 to 0.57) Cleveland Clinic Exercise Treadmill Cohort catalogue → mortality · highest vs lowest tertile
general · n = 122,007 · prospective cohort · Mandsager K, et al. Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing. JAMA Netw Open. 2018;1(6):e183605. PMID 30646266

Remedy and magnitude (16)

↑ 3.82 ml/min/kg (3.17 to 4.48) Exercise training (all types), adults with overweight/obesity · Mean difference in VO2max vs control, pooled across aerobic, resistance, combined and HIIT; 66 RCTs
adults with overweight or obesity · n = 3,964 · meta analysis · van Baak MA, et al. Obes Rev. 2021. PMID 33939229
↑ 1.19 mL/kg/min (0.57 to 1.82) School-based physical activity programmes, children and adolescents · Mean difference in VO2max vs control; 13 studies
at least 12 weeks · children and adolescents aged 6-18 · meta analysis · Neil-Sztramko SE, et al. Cochrane Database Syst Rev. 2021. PMID 34555181
↑ 3.4 mL/kg/min (2.98 to 3.83) Cardiorespiratory training after stroke · Mean difference in VO2 peak vs usual care/no intervention; 9 studies
stroke survivors, mostly ambulatory · n = 438 · meta analysis · Saunders DH, et al. Cochrane Database Syst Rev. 2020. PMID 32196635
↑ 3.52 mL/kg.min (2.47 to 4.57) Short-interval HIIT after stroke · Within-group change in VO2peak at 12 weeks (HIIT); MICT group change 1.71 (0.55-2.86); between-group difference 1.81 (0.58-3.04)
12 wk · 3 d/wk, 10 x 1 min at 80-100% HRR with 1 min at 30% HRR · adults >=6 months post-stroke, mean age 64.9 · n = 82 · rct · Moncion K, et al. Stroke. 2024. PMID 39113181
↑ 3.04 mL.kg-1.min-1 (1.7 to 4.37) Exercise training in coronary artery disease (HRV-guided or predefined) · Change in maximum oxygen uptake after 6 weeks, pooled across both training groups
6 wk · 3 sessions/week · coronary artery disease patients · n = 21 · rct · Manresa-Rocamora A, et al. Int J Environ Res Public Health. 2022. PMID 36078179
↑ 6.2 mL/kg/min (4.2 to 8.3) Guideline-based exercise, sedentary adults with CVD risk factors · Change in cardiorespiratory fitness vs control (EXE vs CON); 8 weeks
8 wk · guideline-based regular exercise · adults aged 49 +/- 9 with low activity and >=1 CVD risk factor · n = 47 · rct · Lee E, et al. Am J Physiol Regul Integr Comp Physiol. 2022. PMID 35785965
↑ 1.5 mL/kg/min (0.4 to 2.7) High-intensity interval training, HFpEF · Change in peak VO2 at 3 months vs guideline-based advice (1.1 vs -0.6 mL/kg/min)
3 x 38 minutes/week; 3 months in clinic · sedentary patients with chronic stable HFpEF, mean age 70 · n = 180 · rct · Mueller S, et al. JAMA. 2021. PMID 33560320
↑ 2 mL/kg/min (0.9 to 3.1) Moderate continuous training, HFpEF · Change in peak VO2 at 3 months vs guideline-based advice (1.6 vs -0.6 mL/kg/min)
5 x 40 minutes/week; 3 months in clinic · sedentary patients with chronic stable HFpEF, mean age 70 · n = 180 · rct · Mueller S, et al. JAMA. 2021. PMID 33560320
↑ 3.6 mL/kg/min Aerobic and resistance exercise, adults 50+ (lifestyle review) · Mean difference in VO2 max reported in a systematic review of 35 lifestyle RCTs
adults aged 50 and above · n = 25,000 · systematic review · Joshi S, et al. Invest Educ Enferm. 2025. PMID 41289530
↑ 17% (12 to 22) High-Intensity Interval Training (HIIT 4x4 min @ 90% HRmax) catalogue · vs Standard care / no intervention
meta analysis · Milanović Z, et al. Sports Med. 2015;45:1469-1481. PMID: 26243014 PMID 26243014
↓ -10% (-10 to -10) Sedentary lifestyle and continuous physical inactivity catalogue · vs Standard care / no intervention
prospective cohort · Mandsager K, et al. JAMA Netw Open. 2018;1:e183605. PMID: 30646262 PMID 30646262
↓ -55% (-70 to -40) Severe chronic obstructive pulmonary disease (COPD) or HFrEF catalogue · vs Standard care / no intervention
clinical guideline · Mancini DM, et al. Circulation. 1991;83:778-786. PMID: 1999029 PMID 1999029
↑ 3.82 mL/kg/min (3.17 to 4.48) Structured exercise training (any modality) in adults with overweight/obesity catalogue · vs no exercise control
adults with overweight or obesity (66 RCTs, 3964 participants) · n = 3,964 · meta analysis · van Baak MA, Pramono A, Battista F, et al. Effect of different types of regular exercise on physical fitness in adults with overweight or obesity: Systematic re PMID 33939229
↑ 3.4 mL/kg/min (2.98 to 3.83) Cardiorespiratory fitness training after stroke catalogue · vs usual care / no intervention
mostly ambulatory stroke survivors (9 studies, 438 participants for VO2 peak) · n = 438 · meta analysis · Saunders DH, Sanderson M, Hayes S, et al. Physical fitness training for stroke patients. Cochrane Database Syst Rev. 2020. PMID 32196635
↑ 3.52 mL/kg/min (2.47 to 4.57) Short-interval HIIT (10 x 1 min at 80-100% HRR), 3 days/week for 12 weeks, after stroke catalogue · vs active comparator (moderate-intensity continuous training)
12 wk · 19.0 min 3 days per week · adults >=6 months post-stroke, mean age 65 · n = 42 · rct · Moncion K, Rodrigues L, De Las Heras B, et al. Cardiorespiratory Fitness Benefits of High-Intensity Interval Training After Stroke: A Randomized Controlled Tria PMID 39113181
↑ 2 mL/kg/min (0.9 to 3.1) Moderate continuous training 5 x 40 min/week, 3 months (HFpEF) catalogue · vs guideline-based physical activity advice
40.0 min 5 times per week, 3 months · sedentary patients with chronic stable HFpEF, mean age 70 · n = 60 · rct · Mueller S, Winzer EB, Duvinage A, et al. Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice o PMID 33560320

Lung function FEV1 (L) · capacity

4 3 3

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Annual FEV1 decline, women not engaged in cleaning (ECRHS), -18.5 ml/yr per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (4)

↓ -39.6 mL/year per year (-64.3 to -12.7) Annual FEV1 decline, persistent normal spirometry (Rotterdam Study) · Median FEV1 change per year in persistent controls re-examined after 4.5 years; lower/upper are the interquartile range, not a CI
ages mean 69.1 +/- 8.9 years at baseline · older adults, Rotterdam Study, re-examined subset · n = 1,603 · prospective cohort · Wijnant SRA, et al. Eur Respir J. 2020. PMID 31601717
↓ -18.5 ml/yr per year Annual FEV1 decline, women not engaged in cleaning (ECRHS) · Mixed-model adjusted change in FEV1 per year over 20 years of follow-up, reference group
ages adults, ECRHS I to III (20 years) · women, European Community Respiratory Health Survey · n = 6,235 · prospective cohort · Svanes O, et al. Am J Respir Crit Care Med. 2018. PMID 29451393
↓ -22.4 ml/yr per year Annual FEV1 decline, women working as occupational cleaners (ECRHS) · Adjusted change in FEV1 per year; vs -18.5 ml/yr in women not engaged in cleaning
ages adults, ECRHS I to III (20 years) · women, European Community Respiratory Health Survey · n = 6,235 · prospective cohort · Svanes O, et al. Am J Respir Crit Care Med. 2018. PMID 29451393
↓ -38 mL/year per year (-61.7 to -14.6) Excess FEV1 decline with chronic bronchitis in COPD (Rotterdam Study) · Additional annual FEV1 decline in COPD subjects with vs without chronic bronchitis over median 6.5 years
ages adults >=45 years · COPD subjects, Rotterdam Study · n = 972 · prospective cohort · Lahousse L, et al. Eur Respir J. 2017. PMID 28798087

Link to healthspan (3)

↑ ratio 1.19 (1.05 to 1.35) Incident CVD with obstructive spirometry in type 2 diabetes → cardiovascular disease · Adjusted subdistribution HR for obstructive physiology vs preserved lung function; median follow-up 13.9 years
UK Biobank participants with type 2 diabetes, free of CVD · n = 16,242 · prospective cohort · Chen C, et al. Diabetes Care. 2025. PMID 39932813
↑ ratio 1.24 (1.14 to 1.34) Incident all-cause dementia per 1 L lower FEV1 → dementia · HR per unit (liter) decrease in FEV1, UK Biobank, mean follow-up 8.65 years
non-demented UK Biobank participants with spirometry · n = 431,834 · prospective cohort · Ma YH, et al. Brain Behav Immun. 2023. PMID 36796705
↑ ratio 1.7 (1.4 to 2.1) All-cause mortality, COPD GOLD 2-4 vs normal spirometry → all-cause mortality · Adjusted HR vs controls (FEV1/FVC >=0.7, FEV1 >=80%); maximum 9.3 years follow-up
older adults, Rotterdam Study, mean age 69.1 · n = 5,487 · prospective cohort · Wijnant SRA, et al. Eur Respir J. 2020. PMID 31601717

Remedy and magnitude (3)

↑ 0.25 L VR-complemented pulmonary rehabilitation in COPD · VR-complemented PR vs comparators (16 RCTs)
COPD · n = 1,052 · meta analysis · Chen Y, et al. J Med Internet Res. 2025;27:e64742. PMID 40193185
↑ 30 ml per year (7 to 53) Tiotropium: slower annual FEV1 decline · Tiotropium vs placebo and ipratropium; difference in FEV1 decline over 1 year
52 wk · stable COPD · n = 8,002 · meta analysis · Barr RG, et al. Thorax. 2006;61(10):854-62. PMID 16844726
↑ 47 ml Smoking cessation: FEV1 gain in the year after quitting (Lung Health Study) · Sustained quitters within the randomized smoking-intervention trial
52 wk · 12-session cessation program with nicotine gum · smokers with mild-to-moderate airway obstruction, mean age 48.5 · n = 3,926 · rct · Scanlon PD, et al. Am J Respir Crit Care Med. 2000;161(2 Pt 1):381-90. PMID 10673175

Arterial stiffness Carotid-femoral pulse wave velocity (m/s) · capacity

4 4 4

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: cf-PWV age slope, healthy men (ELSA-Brasil), 0.05 m/s per year.

Change with age (4)

↑ 52.5% Aortic PWV, older vs younger normal controls · Percent difference in PWV between younger and older normal controls (+52.5%)
ages younger vs older normal controls (abstract frames the contrast as <50 vs >50 y) · normal controls (comparison group of an ESRD study) · n = 260 · cross sectional · Hsu PF, et al. J Chin Med Assoc. 2008. PMID 18436498
↑ 0.05 m/s per year cf-PWV age slope, healthy men (ELSA-Brasil) · Age-related slope of cf-PWV in the risk-factor-free healthy sample, men; whole-cohort slope 0.0919 m/s per year
ages 35-74 y · healthy adults free of major risk factors, men · n = 2,158 · normative study · Baldo MP, et al. Int J Cardiol. 2018. PMID 29111104
↑ 0.061 m/s per year cf-PWV age slope, healthy women (ELSA-Brasil) · Age-related slope of cf-PWV in the risk-factor-free healthy sample, women; whole-cohort slope 0.0960 m/s per year
ages 35-74 y · healthy adults free of major risk factors, women · n = 2,158 · normative study · Baldo MP, et al. Int J Cardiol. 2018. PMID 29111104
↑ 0.3% per year cf-PWV longitudinal progression, apparently healthy middle-aged men · Relative annual change in carotid-femoral PWV over 4.6 years: 0.3% +/- 5.3% per year (mean +/- SD)
ages 40-49 y at baseline · US men free of CVD (ERA JUMP, Pittsburgh) · n = 240 · prospective cohort · El Khoudary SR, et al. Atherosclerosis. 2012. PMID 23040831

Link to healthspan (4)

↑ ratio 1.9 (1.61 to 2.24) All-cause mortality, high vs low aortic PWV → all-cause mortality · Pooled RR high vs low aortic PWV; 11 studies, mean follow-up 7.7 years
17 longitudinal studies, mixed populations · n = 15,877 · meta analysis · Vlachopoulos C, et al. J Am Coll Cardiol. 2010. PMID 20338492
↑ ratio 2.02 (1.68 to 2.42) Cardiovascular mortality, high vs low aortic PWV → cardiovascular mortality · Pooled RR high vs low aortic PWV; 10 studies
17 longitudinal studies, mixed populations · n = 15,877 · meta analysis · Vlachopoulos C, et al. J Am Coll Cardiol. 2010. PMID 20338492
↑ ratio 2.26 (1.89 to 2.7) Total cardiovascular events, high vs low aortic PWV → cardiovascular events · Pooled RR high vs low aortic PWV; 14 studies
17 longitudinal studies, mixed populations · n = 15,877 · meta analysis · Vlachopoulos C, et al. J Am Coll Cardiol. 2010. PMID 20338492
↑ -0.057 SD/y (-0.105 to -0.01) Semantic fluency decline, highest tertile of brachial-ankle PWV → cognitive decline · Adjusted annual change in semantic fluency (SD/y) for highest vs lowest baPWV tertile, BRAVE cohort
adults aged 40-80 free of dementia, Beijing · n = 932 · prospective cohort · Liang J, et al. J Am Heart Assoc. 2024. PMID 39494555

Remedy and magnitude (4)

↓ -0.7 m/s (-1.2 to -0.19) Aerobic exercise, adults with hypertension · Weighted mean difference in PWV vs control, aerobic subgroup (5 groups)
4 or more weeks · adults with hypertension · n = 642 · meta analysis · Lopes S, et al. J Hypertens. 2021. PMID 32833924
↓ -0.74 m/s (-1.41 to -0.08) Combined aerobic and resistance exercise, adults with hypertension · Weighted mean difference in PWV vs control, combined subgroup (6 groups)
4 or more weeks · adults with hypertension · n = 642 · meta analysis · Lopes S, et al. J Hypertens. 2021. PMID 32833924
↓ -0.76 m/s (-1.05 to -0.47) Exercise training (all modes), adults with hypertension · Weighted mean difference in PWV, exercise vs control; 14 RCTs, 15 interventions
interventions lasting 4 or more weeks · adults with hypertension · n = 642 · meta analysis · Lopes S, et al. J Hypertens. 2021. PMID 32833924
↓ -0.98 m/s (-1.24 to -0.73) Isometric resistance exercise, adults with hypertension · Weighted mean difference in PWV vs control, isometric resistance subgroup (2 groups)
4 or more weeks · adults with hypertension · n = 642 · meta analysis · Lopes S, et al. J Hypertens. 2021. PMID 32833924

Heart-rate recovery HR drop at 1 min post-exercise (beats/min) · capacity

2 4 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↓ -5.64 bpm 7-year decline in HRR, young adults with >=2 metabolic syndrome components (CARDIA) · Longitudinal change in HRR (2 min) from baseline to year 7; one component -3.48 bpm; none -2.40 bpm
ages 18-30 years at baseline, re-tested 7 years later · CARDIA study young adults · n = 4,319 · prospective cohort · Kizilbash MA, et al. Eur Heart J. 2006. PMID 16728422
↓ -2.4 bpm 7-year decline in HRR, young adults without metabolic syndrome components (CARDIA) · Longitudinal change in heart rate recovery (max HR minus HR 2 min post-test) from baseline to year 7 in participants with no metabolic syndrome components
ages 18-30 years at baseline, re-tested 7 years later · CARDIA study young adults · n = 4,319 · prospective cohort · Kizilbash MA, et al. Eur Heart J. 2006. PMID 16728422

Link to healthspan (4)

↑ ratio 1.68 (1.51 to 1.88) All-cause mortality, attenuated vs fast HRR → all-cause mortality · Pooled HR attenuated vs fast HRR (referent); 9 prospective cohorts, 2082 cases
general population · n = 41,600 · meta analysis · Qiu S, et al. J Am Heart Assoc. 2017. PMID 28487388
↑ ratio 1.69 (1.05 to 2.71) Cardiovascular events, attenuated vs fast HRR → cardiovascular events · Pooled HR attenuated vs fast HRR; 5 prospective cohorts, 1061 cases
general population · n = 34,267 · meta analysis · Qiu S, et al. J Am Heart Assoc. 2017. PMID 28487388
↑ ratio 1.36 (1.15 to 1.61) Non-cardiovascular death, abnormal HRR (<13 beats/min) → non-cardiovascular mortality · Adjusted HR for abnormal heart rate recovery in a primary prevention exercise-test population; 12.7-year follow-up
patients 30-79 without baseline CVD, Minnesota · n = 13,382 · prospective cohort · Sydo N, et al. Mayo Clin Proc. 2023. PMID 37661140
↑ ratio 2 (1.5 to 2.7) All-cause mortality, abnormal 1-min HRR (<=12 bpm) → all-cause mortality · Adjusted relative risk for HRR <=12 bpm at 1 min vs normal, 6-year follow-up; unadjusted RR 4.0 (3.0-5.2)
adults referred for exercise thallium testing, mean age 57 · n = 2,428 · prospective cohort · Cole CR, et al. N Engl J Med. 1999. PMID 10536127

Remedy and magnitude (3)

↑ 2.74% HIIT (30 s work : 10 s rest), adolescent taekwondo athletes · Percent improvement in heart rate recovery after 8 weeks (HIIT-30S); HIIT-20S 2.57%
8 wk · 24 sessions, 30 min/session · adolescent taekwondo athletes aged 16-20 · n = 30 · rct · Xu N, et al. Eur J Sport Sci. 2025. PMID 40940682
↑ 4.33 bpm (1.15 to 7.52) Exercise training in coronary artery disease (HRR at 2 min) · Change in heart rate recovery at 2 min after 6 weeks, pooled across HRV-guided and predefined training
6 wk · 3 sessions/week · coronary artery disease patients · n = 21 · rct · Manresa-Rocamora A, et al. Int J Environ Res Public Health. 2022. PMID 36078179
↑ 22.95 beat/min (11.72 to 34.18) Exercise training after bariatric surgery (HRR at 60 s) · Between-group absolute change in HRR60s, exercised vs non-exercised women, over a 6-month programme
6-month exercise training programme · women undergoing bariatric surgery · n = 62 · rct · Gil S, et al. Obes Surg. 2021. PMID 33111247

Forced vital capacity FVC (L) · physical parameter on the landscape

3 1 6

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, Peto et al. 2017 (MortalityPredictors.org) anchor cohort (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (3)

↓ -20 mL per year FVC decline in persistent normal-spirometry controls · Median FVC change of -20.0 mL per year (IQR -55.4 to 18.8) over about 4.5 y in subjects with persistently normal spirometry
ages mean age 69.1 y (SD 8.9) · general-population cohort, mean age 69.1 y (Rotterdam Study), persistent controls · prospective cohort · Wijnant SRA, et al. Eur Respir J. 2020. PMID 31601717
↑ 0.368 L Median, ages 40–59 vs 20–39 catalogue · 4.232 → 4.6 (+9%)
ages 40–59 vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 1,138 · cross sectional · Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999;159(1):179-187. PMID 9872837
↑ 0.782 L Median, ages 60+ vs 20–39 catalogue · 4.232 → 5.014 (+18%)
ages 60+ vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 1,138 · cross sectional · Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999;159(1):179-187. PMID 9872837

Link to healthspan (1)

ratio 2.21 (1.14 to 4.3) Lee HM, Le H, Lee BT, Lopez VA, Wong ND. Forced vital capacity paired with Framingham Risk catalogue → mortality · highest vs lowest quartile
general · n = 569 · prospective cohort · Lee HM, Le H, Lee BT, Lopez VA, Wong ND. Forced vital capacity paired with Framingham Risk Score for prediction of all-cause mortality. Eur Respir J. 2010;36(5):1002-1006. PMID 20562119

Remedy and magnitude (6)

↑ SMD 0.87 (0.59 to 1.15) Pursed lip plus diaphragmatic breathing in COPD · Pursed lip breathing combined with diaphragmatic breathing vs control: FVC SMD 0.87 (95% CI 0.59-1.15)
COPD (15 RCTs) · n = 1,098 · meta analysis · Yang Y, et al. Physiother Theory Pract. 2022. PMID 32808571
↑ 0.069 L (0.03 to 0.107) Nerandomilast 18 mg twice daily (PDE4B inhibitor) in idiopathic pulmonary fibrosis catalogue · vs placebo
52 wk · 18.0 mg twice daily · adults with idiopathic pulmonary fibrosis (77.7% on background antifibrotic) · n = 1,177 · rct · Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2025. PMID 40387033
↑ 0.067 L (0.032 to 0.102) Nerandomilast 18 mg twice daily in progressive pulmonary fibrosis (non-IPF) catalogue · vs placebo
52 wk · 18.0 mg twice daily · adults with progressive pulmonary fibrosis (43.5% on background nintedanib) · n = 1,176 · rct · Maher TM, Assassi S, Azuma A, et al. Nerandomilast in Patients with Progressive Pulmonary Fibrosis. N Engl J Med. 2025. PMID 40388329
↑ 0.096 L (0.052 to 0.139) Inhaled treprostinil (12 breaths four times daily) in idiopathic pulmonary fibrosis catalogue · vs placebo
52 wk · 12.0 breaths four times daily · adults with IPF, mean age 71.7, baseline FVC 76.8% predicted, 75% on background antifibrotics · n = 593 · rct · Nathan SD, Smith P, Deng C, et al. Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med. 2026. PMID 41812190
↑ 0.041 L (0.003 to 0.079) Nintedanib 150 mg twice daily in systemic sclerosis-associated ILD catalogue · vs placebo
52 wk · 150.0 mg twice daily · adults with systemic sclerosis-associated ILD (48% on mycophenolate) · n = 576 · rct · Distler O, Highland KB, Gahlemann M, et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019. PMID 31112379
↑ 0.229 L High-frequency chest wall oscillation (airway clearance) in stable bronchiectasis catalogue · vs no intervention
daily, 15 days · adults with stable bronchiectasis (single included study for this outcome) · meta analysis · Lee AL, Burge AT, Holland AE. Airway clearance techniques for bronchiectasis. Cochrane Database Syst Rev. 2015. PMID 26591003

Diffusing capacity DLCO (mL/min/mmHg) · physical parameter

2 1 2

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↓ -0.7 mL/min/mm Hg per year (-0.7 to -0.4) DLCO decline in healthy never-smoking men (Framingham) · Estimated mean annual decline ranges 0.4 to 0.7 mL/min/mmHg/y, accelerating with age; value is the upper (older-age) end
ages 30s-70s · healthy never-smokers (Framingham Heart Study) · n = 881 · prospective cohort · Sangani R, et al. CHEST Pulm. 2024;2(3). PMID 39421758
↓ -0.35 mL/min/mm Hg per year (-0.35 to -0.05) DLCO decline in healthy never-smoking women (Framingham) · Estimated mean annual decline ranges 0.05 to 0.35 mL/min/mmHg/y, accelerating with age; value is the upper (older-age) end
ages 30s-70s · healthy never-smokers (Framingham Heart Study) · n = 881 · prospective cohort · Sangani R, et al. CHEST Pulm. 2024;2(3). PMID 39421758

Link to healthspan (1)

↑ ratio 1.2 Lower DLCO and mortality in systemic sclerosis → mortality · HR for mortality per 10% decrease in diffusing capacity of the lung (EUSTAR cohort, multivariable Cox model); risk rises as DLCO falls
systemic sclerosis (EUSTAR cohort) · n = 5,860 · prospective cohort · Tyndall AJ, et al. Ann Rheum Dis. 2010. PMID 20551155

Remedy and magnitude (2)

↑ 0.4 mmol/kPa/min (0.1 to 0.7) Pirfenidone in progressive pulmonary fibrosis · Pirfenidone vs placebo, change in DLCO
progressive pulmonary fibrosis (non-IPF) · meta analysis · Ghazipura M, et al. Ann Am Thorac Soc. 2022;19(6):1030-1039. PMID 35499847
↑ 10.4 % predicted (4.3 to 16.5) Pirfenidone plus glucocorticoids in radiation-induced lung injury · LS mean difference in change of DLCO% (percent predicted) at week 24 vs glucocorticoids alone
24 wk · pirfenidone 200 mg tid wk1, 300 mg tid wk2, 400 mg tid wk3-24 · grade 2-3 radiation-induced lung injury · n = 134 · rct · Hou Z, et al. Lancet Oncol. 2025;26(12):1552-1562. PMID 41207313

Respiratory muscle strength Maximal inspiratory pressure (cmH2O) · physical parameter

4 3 3

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: MIP lower with age in healthy men (BLSA reference equation), -1.028 cm H2O per year.

Change with age (4)

↓ -0.57 cmH2O per year MIP lower with age in healthy Brazilian men · Age coefficient in prediction equation MIP = 137 - 0.57 x age (R2 0.13)
ages 20-80 · healthy Brazilian men · n = 111 · normative study · Araujo PRS, et al. PLoS One. 2024;19(11):e0313209. PMID 39570848
↓ -0.4 cmH2O per year MIP lower with age in healthy Brazilian women · Age coefficient in prediction equation MIP = 107.3 - 0.4 x age (R2 0.16)
ages 20-80 · healthy Brazilian women · n = 132 · normative study · Araujo PRS, et al. PLoS One. 2024;19(11):e0313209. PMID 39570848
↓ -1.028 cm H2O per year MIP lower with age in healthy men (BLSA reference equation) · Age coefficient in reference equation MIP = 126 - 1.028 x age + 0.343 x weight
ages 20-90 · healthy men (Baltimore Longitudinal Study of Aging) · n = 139 · normative study · Harik-Khan RI, et al. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1459-64. PMID 9817693
↓ -0.694 cm H2O per year MIP lower with age in healthy women (BLSA reference equation) · Age coefficient in MIP = 171 - 0.694 x age + 0.861 x weight - 0.743 x height
ages 20-90 · healthy women (Baltimore Longitudinal Study of Aging) · n = 128 · normative study · Harik-Khan RI, et al. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1459-64. PMID 9817693

Link to healthspan (3)

↓ ratio 0.97 (0.95 to 0.99) Inspiratory muscle strength and all-cause mortality in COPD → all-cause mortality · Pooled HR for inspiratory strength (higher strength, lower hazard); 2 poolable studies
COPD · meta analysis · Mizusawa H, et al. Int J Chron Obstruct Pulmon Dis. 2025;20:4205-4216. PMID 41497970
↑ ratio 1.54 (1.09 to 2.15) Lowest MIP quintile and cardiovascular death (CHS) → cardiovascular mortality · Lowest vs higher MIP quintiles; adjusted for non-pulmonary-function covariates
ages 65+ · community-dwelling older adults free of CHF, MI and stroke (Cardiovascular Health Study) · prospective cohort · van der Palen J, et al. Thorax. 2004;59(12):1063-7. PMID 15563706
↑ ratio 1.48 (1.07 to 2.06) Lowest MIP quintile and myocardial infarction (CHS) → myocardial infarction · Lowest vs higher MIP quintiles; adjusted for non-pulmonary-function covariates
ages 65+ · community-dwelling older adults free of CHF, MI and stroke (Cardiovascular Health Study) · prospective cohort · van der Palen J, et al. Thorax. 2004;59(12):1063-7. PMID 15563706

Remedy and magnitude (3)

↑ 25.12 cmH2O (15.29 to 34.95) Isolated inspiratory muscle training in heart failure · Increase in maximal inspiratory pressure with isolated IMT vs control
heart failure (10 isolated-IMT studies) · meta analysis · Azambuja ACM, et al. Phys Ther. 2020. PMID 32936904
↑ 13 cmH2O Inspiratory muscle training in COPD · Maximal inspiratory pressure (PImax) improvement with inspiratory muscle training vs control across RCTs
COPD (32 RCTs) · meta analysis · Gosselink R, et al. Eur Respir J. 2011. PMID 21282809
↑ SMD 1.235 12-week IMT plus manual therapy vs IMT alone in severe COPD · MIP effect size (Cohen d 1.235, p<0.001) for IMT at 40% of MIP plus 30 min manual therapy vs IMT alone
12 wk · IMT at 40% MIP plus manual therapy, 30 min · severe COPD (GOLD III-IV) · n = 60 · rct · Buran Cirak Y, et al. Clin Respir J. 2022. PMID 35332685

Lactate / ventilatory threshold Lactate threshold, % of VO2max (%VO2max; W) · physical parameter

2 3 2

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Ventilatory threshold decline with age in healthy men (longitudinal), -0.03 L/min per year.

Change with age (2)

↓ -0.02 L/min per year Ventilatory threshold decline with age in healthy men (cross-sectional) · VO2 at ventilatory threshold, treadmill graded test, cross-sectional age slope
ages 30-69 · healthy men in a preventive medicine service · n = 816 · cross sectional · Nelson MD, et al. Med Sci Sports Exerc. 2010;42(2):255-64. PMID 19927033
↓ -0.03 L/min per year Ventilatory threshold decline with age in healthy men (longitudinal) · VO2 at ventilatory threshold, within-person slope over mean 7.3 y follow-up
ages 30-69 · healthy men who returned for >= 5 visits · n = 87 · prospective cohort · Nelson MD, et al. Med Sci Sports Exerc. 2010;42(2):255-64. PMID 19927033

Link to healthspan (3)

↓ ratio 0.76 (0.66 to 0.85) Anaerobic threshold and complications after colorectal cancer surgery → postoperative complications · Pooled OR for VO2 at anaerobic threshold (higher AT, lower odds)
adults undergoing colorectal cancer surgery · n = 1,418 · meta analysis · Lee CHA, et al. Dis Colon Rectum. 2018;61(3):400-409. PMID 29377872
↓ ratio 0.52 Anaerobic threshold and in-hospital mortality after hepatobiliary surgery → in-hospital mortality · Odds ratio for anaerobic threshold (higher AT, lower odds); scaling not stated
ages 26-86 (mean 66) · adults undergoing major hepatobiliary surgery · n = 389 · prospective cohort · Snowden CP, et al. Ann Surg. 2013;257(6):999-1004. PMID 23665968
↑ ratio 6.35 (1.84 to 29.8) Anaerobic threshold < 10.2 mL/kg/min and 30-day mortality after AAA repair → 30-day mortality · Multivariable OR, AT below 10.2 ml per kg per min
elective abdominal aortic aneurysm repair · n = 415 · prospective cohort · Hartley RA, et al. Br J Surg. 2012;99(11):1539-46. PMID 23001820

Remedy and magnitude (2)

↑ 5% 10-day heat acclimation, power at lactate threshold, cool conditions · Power output at lactate threshold increased by 5% (3.88 vs 4.09 W/kg) when tested in a cool environment (13 C); controls unchanged
10-day heat acclimation, ~50% VO2max in 40 C · trained cyclists · n = 12 · rct · Lorenzo S, et al. J Appl Physiol. 2010. PMID 20724560
↑ 5% 10-day heat acclimation, power at lactate threshold, hot conditions · Power output at lactate threshold increased by 5% (3.45 vs 3.60 W/kg) when tested in a hot environment (38 C); controls unchanged
10-day heat acclimation, ~50% VO2max in 40 C · trained cyclists · n = 12 · rct · Lorenzo S, et al. J Appl Physiol. 2010. PMID 20724560

Cardiac structure and function

Left-ventricular ejection fraction LVEF (echo / MRI) (%) · physical parameter on the landscape

2 4 10

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, Peto et al. 2017 (MortalityPredictors.org) anchor cohort (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (2)

↑ 5.024 % Median, ages 40–59 vs 20–39 catalogue · 57.78 → 62.8 (+9%)
ages 40–59 vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 20,854 · cross sectional · What is a normal left ventricular ejection fraction in healthy adults? A meta-analysis of population-based echocardiographic studies (pooled n=10,427). J Cardiovasc Imaging. 2025. PMID 41572417
↑ 10.676 % Median, ages 60+ vs 20–39 catalogue · 57.78 → 68.45 (+18%)
ages 60+ vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 20,854 · cross sectional · What is a normal left ventricular ejection fraction in healthy adults? A meta-analysis of population-based echocardiographic studies (pooled n=10,427). J Cardiovasc Imaging. 2025. PMID 41572417

Link to healthspan (4)

↑ ratio 3.48 (1.84 to 6.58) LVEF <=55% vs >60% and mortality in women with severe degenerative mitral regurgitation → all-cause mortality · Adjusted HR for LVEF <=55% vs >60% after mitral valve surgery, women
women undergoing surgery for severe degenerative mitral regurgitation · n = 598 · prospective cohort · Kwak S et al., JAMA network open, 2025 PMID 40163120
↑ ratio 2.21 (1.36 to 3.58) LVEF >55% to 60% vs >60% and mortality in women with severe degenerative mitral regurgitation → all-cause mortality · Adjusted HR for LVEF 55-60% vs >60% after mitral valve surgery, women
women undergoing surgery for severe degenerative mitral regurgitation · n = 598 · prospective cohort · Kwak S et al., JAMA network open, 2025 PMID 40163120
↑ ratio 3.38 Lower ejection fraction and 5-year mortality, early after Fontan → 5-year all-cause mortality · Hazard ratio per 10% lower EF, group early (0.5-5 years postoperatively)
Fontan operation, 0.5-5 years postoperatively · n = 387 · prospective cohort · Ohuchi H et al., American heart journal, 2017 PMID 28625386
ratio 6 (2.9 to 12) McDonagh TA, Cunningham AD, Morrison CE, McMurray JJ, Ford I, Morton JJ, Dargie HJ. Left v catalogue → mortality · highest vs lowest quartile
general · n = 1,252 · prospective cohort · McDonagh TA, Cunningham AD, Morrison CE, McMurray JJ, Ford I, Morton JJ, Dargie HJ. Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population. Heart. 2001;86(1):21-26. PMID 11410555

Remedy and magnitude (10)

0.32 mL (-1.83 to 2.46) HIIT vs moderate-intensity continuous training · Weighted mean difference in LVEF, 22 RCTs
coronary artery disease · n = 1,364 · meta analysis · Gao C et al., PloS one, 2025 PMID 39977401
↑ 4.03 % (2.9 to 5.16) Sacubitril-valsartan (ARNI) vs conventional treatment · Mean difference in LVEF, 26 studies
heart failure with end-stage kidney disease on maintenance dialysis · n = 2,494 · meta analysis · Nguyen DV et al., European journal of heart failure, 2025 PMID 39252524
↑ 7.04 % (3.19 to 10.9) Sacubitril-valsartan, pre/post change · Mean change in LVEF in studies including hypertensive patients with heart failure
hypertension with end-stage kidney disease on dialysis (heart failure subgroup for LVEF) · meta analysis · Nguyen DV et al., Journal of hypertension, 2025 PMID 39927814
↕ -3.6 % (-5.5 to -1.8) Cardioprotection (neurohormonal antagonists) after GLS-defined cardiotoxicity · Adjusted difference in 12-month change in MRI LVEF vs usual care
anthracycline-treated patients with isolated GLS reduction (GLS-CTRCD) · n = 105 · rct · Marwick TH et al., European heart journal, 2024 PMID 39217601
↕ -1.5 % (-2.9 to -0.1) Exercise-based cardio-oncology rehabilitation (ONCORE) · Attenuated LVEF decline vs usual care with exercise recommendation during anthracycline and/or anti-HER2 therapy
early-stage breast cancer receiving anthracyclines and/or anti-HER2 antibodies · n = 122 · rct · Díaz-Balboa E et al., Progress in cardiovascular diseases, 2024 PMID 38395212
↑ 5.1 % G-CSF early after extensive STEMI · Improvement in LVEF from baseline to 6 months, G-CSF plus standard of care vs standard of care alone
STEMI with LVEF <=45% after percutaneous coronary intervention · n = 119 · rct · Achilli F et al., Circulation research, 2019 PMID 31138020
↑ 4.03 % (2.9 to 5.16) Sacubitril/valsartan (ARNI) in heart failure with end-stage kidney disease catalogue · vs conventional therapy
twice daily · heart failure patients with ESKD on dialysis (26 studies) · n = 2,494 · meta analysis · Nguyen DV, Le TN, Truong BQ, et al. Eur J Heart Fail. 2025. PMID 39252524
↑ 7.36 % (4.94 to 9.79) Corticosteroids for viral myocarditis catalogue · vs no corticosteroid / conventional therapy
daily · adults and children with viral myocarditis (8 RCTs) · n = 719 · meta analysis · Chen HS, Wang W, Wu SN, Liu JP. Cochrane Database Syst Rev. 2013. PMID 24136037
↓ -4.8 % (-6.4 to -3.3) Aficamten (cardiac myosin inhibitor) catalogue · vs placebo
24 wk · 20.0 mg daily · adults with obstructive HCM (SEQUOIA-HCM) · n = 282 · rct · Hegde SM, Claggett BL, Wang X, et al. J Am Coll Cardiol. 2024. PMID 39217556
↓ -5.3 % (-5.9 to -4.1) Mavacamten (cardiac myosin inhibitor) catalogue · vs placebo
48 wk · 5.0 mg daily · adults with nonobstructive HCM · n = 580 · rct · Desai MY, Okushi Y, Jadam S, et al. J Am Coll Cardiol. 2025. PMID 40864019

Global longitudinal strain LV global longitudinal strain (%) · physical parameter on the landscape

2 4 6

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, Peto et al. 2017 (MortalityPredictors.org) anchor cohort (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (2)

↓ -1.6 % Median, ages 40–59 vs 20–39 catalogue · -18.4 → -20 (+9%)
ages 40–59 vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 2,658 · cross sectional · Nyberg J, Jakobsen EO, Ostvik A, Holte E, Stolen S, Lovstakken L, Grenne B, Dalen H. Echocardiographic Reference Ranges of Global Longitudinal Strain for All Cardiac Chambers Using Guideline-Directed Dedicated Views. JACC Cardiovasc Imaging. 2023;16(12):1516-1531. PMID 37921718
↓ -3.4 % Median, ages 60+ vs 20–39 catalogue · -18.4 → -21.8 (+18%)
ages 60+ vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 2,658 · cross sectional · Nyberg J, Jakobsen EO, Ostvik A, Holte E, Stolen S, Lovstakken L, Grenne B, Dalen H. Echocardiographic Reference Ranges of Global Longitudinal Strain for All Cardiac Chambers Using Guideline-Directed Dedicated Views. JACC Cardiovasc Imaging. 2023;16(12):1516-1531. PMID 37921718

Link to healthspan (4)

↑ ratio 1.24 (1.1 to 1.39) Decreased LV global longitudinal strain and outcome in HFpEF → cardiovascular death or heart failure hospitalisation · Pooled HR per 5% decrease in GLS, 46 studies
heart failure with preserved ejection fraction · n = 20,056 · meta analysis · Wang N et al., European journal of heart failure, 2024 PMID 38714362
↑ ratio 1.08 (1.04 to 1.12) GLS and all-cause mortality in wild-type transthyretin cardiac amyloidosis → all-cause mortality · Independent HR for baseline GLS; increment not stated in the abstract
wild-type transthyretin amyloid cardiomyopathy, median age 81.5 years · n = 816 · prospective cohort · Debonnaire P et al., Circulation. Cardiovascular imaging, 2026 PMID 41342126
↑ ratio 1.07 (1.01 to 1.13) GLS and all-cause mortality after coronary artery bypass grafting → all-cause mortality · Adjusted for EuroSCORE-II; HR per 1% absolute decrease in GLS
patients after coronary artery bypass grafting · n = 709 · prospective cohort · Olsen FJ et al., Heart (British Cardiac Society), 2021 PMID 33526506
ratio 1.45 (1.19 to 1.77) Stanton T, Leano R, Marwick TH. Prediction of all-cause mortality from global longitudinal catalogue → mortality · per 1 SD
general · n = 546 · prospective cohort · Stanton T, Leano R, Marwick TH. Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring. Circ Cardiovasc Imaging. 2009;2(5):356-364. PMID 19808623

Remedy and magnitude (6)

↓ -0.4 % (-0.8 to -0.05) Mavacamten in non-obstructive HCM · Change in LV GLS at week 48 among patients keeping LVEF >=50%
48 wk · 5 mg/d titrated 1-15 mg by LVEF · symptomatic non-obstructive hypertrophic cardiomyopathy · n = 212 · rct · Desai MY et al., Journal of the American College of Cardiology, 2025 PMID 40864019
↑ 2.5 % Sacubitril-valsartan during anthracycline chemotherapy (SARAH) · Change in GLS over 6 months vs placebo in patients with elevated troponin I
anthracycline-treated patients with elevated cardiac troponin I (80.7% breast cancer) · n = 114 · rct · Bonatto MG et al., Circulation, 2025 PMID 41230611
↑ 2.4 % G-CSF early after extensive STEMI · Improvement in GLS from baseline to 6 months, G-CSF plus standard of care vs standard of care alone
STEMI with LVEF <=45% after percutaneous coronary intervention · n = 119 · rct · Achilli F et al., Circulation research, 2019 PMID 31138020
↓ -0.9 % (-1.5 to -0.2) Sacubitril/valsartan during anthracycline breast-cancer therapy (PRADA II) catalogue · vs placebo
97.0 mg sacubitril (+103 mg valsartan) twice daily, 18 months · women with early breast cancer receiving anthracycline-containing therapy, mean age 54 · n = 138 · rct · Omland T, Heck SL, Holte E, et al. Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Cli PMID 40884047
↑ 3.34 % (2.93 to 3.76) Anabolic-androgenic steroid use in resistance-trained athletes catalogue · vs active (non-using resistance-trained athletes)
male resistance-trained athletes (834 AAS users vs 754 non-users), mean age 32 · n = 2,000 · meta analysis · Cavalcante DN, Romariz L, Neto A, et al. Anabolic-androgenic steroids on cardiac structure and function in resistance-trained athletes: A systematic review and PMID 40945618
↓ -0.1 % (-1.2 to 1.1) Oral cannabidiol (up to 10 mg/kg twice daily) in acute myocarditis catalogue · vs placebo
12 wk · 10.0 mg/kg twice daily · adults with mild-to-moderate acute myocarditis, baseline GLS -15.3% · n = 109 · rct · McNamara DM, Cooper LT, Friedrich MG, et al. Impact of cannabidiol on myocardial recovery in patients with acute myocarditis: primary results of the ARCHER stud PMID 41711722

Left-ventricular mass LV mass index (g/m2) · physical parameter

3 4 4

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: LV mass longitudinal change per decade, men (MESA), 8 g per decade.

Change with age (3)

↓ -0.3 g per year LV mass by cardiac MRI, cross-sectional age slope (MESA) · LV mass decreased with age (-0.3 g per year) while mass-to-volume ratio rose (+5 mg/mL per year)
ages MESA baseline adults · adults without overt cardiovascular disease (MESA) · n = 5,004 · cross sectional · Cheng S, et al. Circ Cardiovasc Imaging. 2009. PMID 19808592
↑ 8 g per decade LV mass longitudinal change per decade, men (MESA) · Longitudinal LV mass change over median 9.4 years of follow-up, mixed-effects model, men
ages 54-94 y at follow-up · adults free of clinical CVD at baseline (MESA), men · n = 2,935 · prospective cohort · Eng J, et al. Radiology. 2016. PMID 26485617
↓ -1.6 g per decade LV mass longitudinal change per decade, women (MESA) · Longitudinal LV mass change over median 9.4 years of follow-up, mixed-effects model, women
ages 54-94 y at follow-up · adults free of clinical CVD at baseline (MESA), women · n = 2,935 · prospective cohort · Eng J, et al. Radiology. 2016. PMID 26485617

Link to healthspan (4)

↑ ratio 1.24 (1.15 to 1.33) Echo LV mass index and incident CVD, adults >=65 y (CHS) → cardiovascular disease events · Adjusted HR per 1-SD higher echo-LVMI for CVD (CHD, heart failure, stroke) over 10 years
community adults >=65 y (Cardiovascular Health Study) · n = 2,577 · prospective cohort · Desai CS, et al. Am J Cardiol. 2016. PMID 27457431
↑ ratio 1.51 (1.4 to 1.62) Echo LV mass index and incident heart failure, adults >=65 y (CHS) → incident heart failure · Adjusted HR per 1-SD higher echo-LVMI for heart failure over 10 years
community adults >=65 y (Cardiovascular Health Study) · n = 2,577 · prospective cohort · Desai CS, et al. Am J Cardiol. 2016. PMID 27457431
↑ ratio 4.3 (1.2 to 13.4) LV mass index top vs bottom quintile and all-cause death, essential hypertension → all-cause mortality · RR of all-cause death, fifth vs first LV mass quintile
untreated uncomplicated essential hypertension · n = 1,925 · prospective cohort · Schillaci G, et al. Hypertension. 2000. PMID 10679501
↑ ratio 3.5 (1.8 to 6.8) LV mass index top vs bottom quintile and cardiovascular events, essential hypertension → major cardiovascular events · Adjusted RR of a major cardiovascular event, fifth vs first gender-specific LV mass quintile (adjusted incl. 24-h ambulatory BP)
untreated uncomplicated essential hypertension · n = 1,925 · prospective cohort · Schillaci G, et al. Hypertension. 2000. PMID 10679501

Remedy and magnitude (4)

↓ -8.44 g/m2 (-11.83 to -5.06) Dapagliflozin in chronic kidney disease (DECODE-CKD) · Placebo-corrected change in LV mass index
chronic kidney disease, mean age 67.5 years · n = 222 · rct · Bartholdy KV et al., NEJM evidence, 2025 PMID 41147829
↓ -3.8 g/m2 (-7.1 to -0.5) Mavacamten in non-obstructive HCM (ODYSSEY-HCM) · Placebo-corrected change in LV mass index at week 48
48 wk · 5 mg/d titrated 1-15 mg by LVEF · symptomatic non-obstructive hypertrophic cardiomyopathy · n = 580 · rct · Desai MY et al., Journal of the American College of Cardiology, 2025 PMID 40864019
↓ -15 g/m2 (-25 to -6) Aficamten in obstructive HCM (SEQUOIA-HCM CMR substudy) · Placebo-relative change in LV mass index by CMR
24 wk · 5-20 mg daily · symptomatic obstructive hypertrophic cardiomyopathy · n = 50 · rct · Masri A et al., Journal of the American College of Cardiology, 2024 PMID 39217563
↓ -6.83 g/m2 Sacubitril/valsartan vs olmesartan in hypertension with elevated pulse pressure · Change in MRI LV mass index from baseline to 52 weeks
52 wk · essential hypertension with elevated pulse pressure · n = 114 · rct · Schmieder RE et al., European heart journal, 2017 PMID 29029087

Diastolic function Mitral E/e ratio / e velocity (ratio; cm/s) · physical parameter

2 3 5

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: E/e' ratio per decade of age, Flemish population sample (FLEMENGHO), 0.38 E/e' ratio per decade · the age range was not stated, so ages 30–80 are assumed.

Change with age (2)

↑ 0.5 E/e' ratio per decade E/e' ratio per decade of age, European population sample (EPOGH) · Partial regression coefficient for age (+10 years) on E/e', mutually adjusted for sex, BMI, heart rate and blood pressure
ages adult population sample (mean 44.5 y) · random population samples, Italy, Poland and Russia · n = 476 · cross sectional · Kloch-Badelek M, et al. Cardiovasc Ultrasound. 2012. PMID 22429658
↑ 0.38 E/e' ratio per decade E/e' ratio per decade of age, Flemish population sample (FLEMENGHO) · Partial regression coefficient for age (+10 years) on E/e', mutually adjusted for sex, BMI, heart rate, blood pressure and LV mass index
ages adult population sample (mean 51 y) · random population sample, Belgium · n = 782 · cross sectional · Kloch-Badelek M, et al. Cardiovasc Ultrasound. 2012. PMID 22429658

Link to healthspan (3)

↑ ratio 1.7 (1.3 to 2.2) Asymptomatic LV diastolic dysfunction and incident heart failure (meta-analysis) → incident heart failure · Pooled maximally adjusted relative risk of overt HF for asymptomatic LV diastolic dysfunction
cohort studies of adults with asymptomatic LV dysfunction · meta analysis · Echouffo-Tcheugui JB, et al. JACC Heart Fail. 2016. PMID 26682794
↑ ratio 1.58 (1.2 to 2.08) Moderate diastolic dysfunction and all-cause mortality (normal EF) → all-cause mortality · Grade II (pseudonormal) vs normal diastolic function, propensity-matched hazard ratio
outpatients with ejection fraction >=55% referred for echocardiography · n = 36,261 · prospective cohort · Halley CM, et al. Arch Intern Med. 2011. PMID 21709107
↑ ratio 1.84 (1.29 to 2.62) Severe diastolic dysfunction and all-cause mortality (normal EF) → all-cause mortality · Grade III (restrictive) vs normal diastolic function, propensity-matched hazard ratio
outpatients with ejection fraction >=55% referred for echocardiography · n = 36,261 · prospective cohort · Halley CM, et al. Arch Intern Med. 2011. PMID 21709107

Remedy and magnitude (5)

0.87 E/e' ratio (-11.09 to 12.83) Supervised exercise training, E/e' in HFpEF (RCT meta-analysis, null) · Weighted mean difference in E/e' after supervised exercise training, 7 RCTs; not significant (I2 = 69%)
supervised exercise training, 12-48 weeks · heart failure with preserved ejection fraction · n = 346 · meta analysis · Sebastian SA, et al. Curr Probl Cardiol. 2024. PMID 38311273
↓ -1.47 E/e' ratio (-1.83 to -1.1) SGLT2 inhibitors, E/e' ratio (RCT meta-analysis) · SGLT2 inhibitor vs control mean difference in E/e', 15 RCTs, with or without heart failure
patients with or without heart failure · n = 1,343 · meta analysis · Fan G, et al. Eur J Intern Med. 2023. PMID 37062643
↑ SMD 0.58 (0.09 to 1.07) Exercise training, early diastolic velocity e' in type 2 diabetes (meta-analysis) · Exercise training vs control, standardised mean difference in e', 6 randomised and non-randomised trials
type 2 diabetes · n = 441 · meta analysis · Anand V, et al. J Cardiopulm Rehabil Prev. 2018. PMID 30142130
↓ -2.38 E/e' ratio (-3.47 to -1.28) Exercise training, E/E' ratio in HFpEF (meta-analysis) · Exercise vs control mean difference in E/E', 5 studies
heart failure with preserved ejection fraction · n = 204 · meta analysis · Pearson MJ, et al. Heart Fail Rev. 2017. PMID 28229273
↓ -2.85 E/e' ratio (-3.66 to -2.04) Exercise training, E/E' ratio in HFrEF (meta-analysis) · Exercise vs control mean difference in E/E', 6 studies
heart failure with reduced ejection fraction · n = 266 · meta analysis · Pearson MJ, et al. Heart Fail Rev. 2017. PMID 28229273

Left-atrial volume Indexed left-atrial volume (mL/m2) · physical parameter

0 3 4

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (0)

no quantified finding yet

Link to healthspan (3)

ratio 0.77 (0.58 to 1.02) LA maximal volume index and incident dementia (ARIC, null) → incident dementia · Highest vs lowest quintile of LA maximal volume index; LA function measures, not size, were associated with dementia
community adults ~75 y without AF or stroke (ARIC) · n = 4,096 · prospective cohort · Wang W, et al. JAMA. 2022. PMID 35315884
↑ 42% Severe LAVI enlargement and mortality, preserved EF → all-cause mortality · Severe LAVI (>=40 mL/m2) vs normal (<=28 mL/m2): 42% increased risk of mortality
clinical echocardiography cohort with preserved ejection fraction · n = 36,561 · prospective cohort · Patel DA, et al. Mayo Clin Proc. 2011. PMID 21803955
↑ 43% Larger LA volume and incident atrial fibrillation, adults >=65 y → incident atrial fibrillation · A 30% larger LA volume was associated with a 43% greater risk of AF (Cox model adjusted for age, sex, valvular disease, hypertension)
Olmsted County residents >=65 y in sinus rhythm with echocardiograms · n = 1,655 · prospective cohort · Tsang TS, et al. Mayo Clin Proc. 2001. PMID 11357793

Remedy and magnitude (4)

↓ -2.6 mL/m2 (-4.7 to -1.11) Mavacamten in non-obstructive HCM (ODYSSEY-HCM) · Change in left atrial volume index at week 48 in patients without atrial fibrillation
48 wk · 5 mg/d titrated 1-15 mg by LVEF · symptomatic non-obstructive hypertrophic cardiomyopathy, no atrial fibrillation · rct · Desai MY et al., Journal of the American College of Cardiology, 2025 PMID 40864019
↓ -13 mL/m2 (-19 to -7) Aficamten in obstructive HCM (SEQUOIA-HCM CMR substudy) · Placebo-relative change in left atrial volume index by CMR
24 wk · 5-20 mg daily · symptomatic obstructive hypertrophic cardiomyopathy · n = 50 · rct · Masri A et al., Journal of the American College of Cardiology, 2024 PMID 39217563
↑ 6.9 mL/m2 (0 to 13.7) Sacubitril/valsartan vs valsartan (PARABLE) · Change in maximal left atrial volume index over the trial
pre-HFpEF (hypertension or diabetes, elevated natriuretic peptide, LAVI >28 mL/m2, EF >50%), median age 72 years · n = 250 · rct · Ledwidge M et al., JAMA cardiology, 2023 PMID 36884247
↓ -7.5 mL/m2 (-9 to -6.1) Mavacamten in obstructive HCM (EXPLORER-HCM) · Change in left atrial volume index over 30 weeks
symptomatic obstructive hypertrophic cardiomyopathy · n = 251 · rct · Hegde SM et al., Journal of the American College of Cardiology, 2021 PMID 34915982

Stroke volume and cardiac output Stroke volume / cardiac index (mL; L/min/m2) · physical parameter

4 2 5

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Stroke volume longitudinal change per decade, men (MESA), -8.8 mL per decade.

Change with age (4)

↓ -0.4 mL per year Stroke volume by cardiac MRI, cross-sectional age slope (MESA) · Age associated with a fall in stroke volume of 0.4 mL per year despite ejection fraction +0.1% per year
ages MESA baseline adults · adults without overt cardiovascular disease (MESA) · n = 5,004 · cross sectional · mechanism: smaller end-diastolic volume (-0.8 mL per year) · Cheng S, et al. Circ Cardiovasc Imaging. 2009. PMID 19808592
↓ -16% Resting cardiac index across six decades, healthy women (BLSA) · Resting sitting cardiac index decreased 16% over the six-decade age span in women (no age change in men)
ages 22-86 y · rigorously screened healthy sedentary volunteers, women (BLSA) · n = 79 · cross sectional · Fleg JL, et al. J Appl Physiol. 1995. PMID 7775334
↓ -8.8 mL per decade Stroke volume longitudinal change per decade, men (MESA) · Longitudinal stroke volume change over median 9.4 years, mixed-effects model, men
ages 54-94 y at follow-up · adults free of clinical CVD at baseline (MESA), men · n = 2,935 · prospective cohort · Eng J, et al. Radiology. 2016. PMID 26485617
↓ -8.6 mL per decade Stroke volume longitudinal change per decade, women (MESA) · Longitudinal stroke volume change over median 9.4 years, mixed-effects model, women
ages 54-94 y at follow-up · adults free of clinical CVD at baseline (MESA), women · n = 2,935 · prospective cohort · Eng J, et al. Radiology. 2016. PMID 26485617

Link to healthspan (2)

↑ r = 0.64 Change in cardiac index and change in exercise capacity → 6-minute walking distance · Meta-regression correlation between change in cardiac index and change in 6-minute walking distance
pulmonary arterial hypertension (treatment trials) · meta analysis · Savarese G et al., The European respiratory journal, 2013 PMID 23100502
↑ ratio 2.5 (1.3 to 4.55) Higher cardiac index and mortality, late after Fontan → 5-year all-cause mortality · HR for higher cardiac index in the group >=15 years after Fontan
Fontan operation, >=15 years postoperatively · n = 161 · prospective cohort · Ohuchi H et al., American heart journal, 2017 PMID 28625386

Remedy and magnitude (5)

↑ 22.5% Adjunctive milrinone in septic shock · Median percentage change in cardiac index at 6 h vs placebo
septic shock with poor tissue perfusion or impaired LV systolic function · n = 64 · rct · Tongyoo S et al., Annals of medicine, 2025 PMID 40138463
↑ 10 mL (0 to 20) Oral ketone ester, 2 weeks · Placebo-controlled change in stroke volume at peak exercise (crossover)
2 wk · 25 g D-beta-hydroxybutyrate-(R)-1,3-butanediol, four times daily · type 2 diabetes with heart failure with preserved ejection fraction · n = 24 · rct · Gopalasingam N et al., Circulation, 2024 PMID 39162035
↑ 0.2 L/min (0.1 to 0.3) Oral ketone ester, 2 weeks (cardiac output) · Placebo-controlled change in resting cardiac output over a 4-hour period
2 wk · 25 g D-beta-hydroxybutyrate-(R)-1,3-butanediol, four times daily · type 2 diabetes with heart failure with preserved ejection fraction · n = 24 · rct · Gopalasingam N et al., Circulation, 2024 PMID 39162035
↑ 1.21 L/min (0.26 to 2.15) Resistance exercise training · Change in cardiac output, 3 days/week vs non-exercise control
9 wk · 3 days/week resistance exercise · middle-aged and older adults with untreated elevated blood pressure or stage-1 hypertension · n = 26 · rct · Banks NF et al., American journal of physiology. Heart and circulatory physiology, 2024 PMID 37975709
↑ 10% Aerobic high-intensity interval training · Change in stroke volume after 8 weeks of interval running
8 wk · 3 days/week; 4 x 4 min or 15/15 s intervals at 90-95% HRmax · healthy, moderately trained men · n = 40 · rct · Helgerud J et al., Medicine and science in sports and exercise, 2007 PMID 17414804

Maximal heart rate Peak heart rate on exercise test (beats/min) · physical parameter

2 4 1

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Decline in maximal heart rate over 5 years, asymptomatic men, -1 beat/min per year.

Change with age (2)

↓ -9 beats per minute per decade Decline in peak heart rate with age, Lithuanian adults · Cross-sectional decline per age decade
ages 20-60 years · healthy adults, cycle ergometer test · n = 168 · cross sectional · Grigaliūnienė A et al., Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese, 2013 PMID 23557610
↓ -1 beat/min per year Decline in maximal heart rate over 5 years, asymptomatic men · Longitudinal treadmill change, two Bruce-protocol tests five years apart
ages 45-72 years · asymptomatic men not in any fitness programme · n = 169 · prospective cohort · Cumming GR et al., Canadian journal of applied sport sciences. Journal canadien des sciences appliquees au sport, 1984 PMID 6733837

Link to healthspan (4)

↓ -3% Peak exercise heart rate and all-cause mortality, asymptomatic women → all-cause mortality · Risk of death reduced by 3% for every 1-beat-per-minute increase in peak HR, adjusted for exercise capacity and risk factors
asymptomatic women (St. James Women Take Heart) · n = 5,437 · prospective cohort · Gulati M, et al. Circulation. 2010. PMID 20585008
↑ ratio 1.84 (1.13 to 3) Failure to reach 85% of age-predicted maximum heart rate and mortality → all-cause mortality · Adjusted RR of death for chronotropic incompetence (<85% age-predicted max HR), adjusted for thallium perfusion defects and confounders
patients referred for treadmill thallium testing, not on beta-blockers · n = 2,953 · prospective cohort · Lauer MS, et al. JAMA. 1999. PMID 10022108
↑ ratio 1.75 (1.11 to 2.74) Failure to achieve target heart rate and incident CHD, Framingham Offspring men → incident coronary heart disease · Adjusted HR for incident coronary heart disease, failure to achieve 85% of age-predicted maximum heart rate
men free of CHD, not on beta-blockers (Framingham Offspring) · n = 1,575 · prospective cohort · Lauer MS, et al. Circulation. 1996. PMID 8608620
↓ ratio 0.56 (0.34 to 0.89) Maximal exercise heart rate and cardiovascular mortality, healthy men → cardiovascular mortality · Adjusted RR of cardiovascular death, maximal exercise-induced heart rate quartiles 3-4 vs quartile 1, 16-year follow-up
apparently healthy men 40-59 y · n = 1,960 · prospective cohort · Sandvik L, et al. Coron Artery Dis. 1995. PMID 8574463

Remedy and magnitude (1)

↑ 4.21 bpm (1.07 to 7.36) HIIT vs moderate-intensity continuous training · Weighted mean difference in peak heart rate, 22 RCTs
coronary artery disease · n = 1,364 · meta analysis · Gao C et al., PloS one, 2025 PMID 39977401

Vascular

Flow-mediated dilation Brachial artery FMD (%) · physical parameter

2 1 6

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↑ 12.1 % Healthy centenarians vs younger adults · FMD 12.1 +/- 4.3% in centenarians (101 +/- 1 y) vs 8.6 +/- 5.3% in controls (41 +/- 14 y), P<0.05; effect value is the centenarian FMD
ages 101 +/- 1 y vs 41 +/- 14 y · healthy centenarians vs younger controls · cross sectional · Buscemi C, et al. Exp Gerontol, 2024 PMID 38728795
↓ 4.7 % Healthy women across the menopause transition · FMD 9.9 +/- 2.1% premenopausal (32 +/- 6 y) falling stepwise to 4.7 +/- 1.7% late postmenopausal (61 +/- 4 y), P<0.001; effect value is the late-postmenopausal FMD
ages 32 +/- 6 y vs 61 +/- 4 y (range 22-70 y) · healthy women aged 22-70 y · n = 132 · cross sectional · Moreau KL, et al. J Clin Endocrinol Metab, 2012 PMID 22969140

Link to healthspan (1)

↓ ratio 0.9 (0.88 to 0.92) FMD and cardiovascular events / all-cause mortality → cardiovascular events and all-cause mortality · Pooled multivariable RR per 1% increase in brachial FMD, 32 studies meta-analysed
mixed populations · n = 15,191 · meta analysis · Xu Y, et al. Eur Heart J Cardiovasc Imaging, 2014 PMID 24399339

Remedy and magnitude (6)

↑ 2.18 % (1.78 to 2.58) Exercise training in type 2 diabetes · Pooled weighted mean difference vs control, 13 RCTs
type 2 diabetes · meta analysis · Qiu B, et al. Front Endocrinol, 2024 PMID 38596227
↑ 2.62 % (1.42 to 3.82) High-intensity interval training in type 2 diabetes · HIIT subgroup WMD vs control in the same meta-analysis
type 2 diabetes · meta analysis · Qiu B, et al. Front Endocrinol, 2024 PMID 38596227
↑ 2.37 % (0.61 to 4.14) Resistance exercise training · 3 days/week vs non-exercise control; mean change in FMD
9 wk · 3 days/week · middle-aged and older adults with elevated BP or stage-1 hypertension · n = 26 · rct · Banks NF, et al. Am J Physiol Heart Circ Physiol, 2024 PMID 37975709
↑ 45% High-resistance inspiratory muscle strength training · 6 weeks of IMST vs sham training; brachial FMD improved about 45% with IMST (P<0.01), unchanged with sham (P=0.73)
6 wk · 30 breaths/day, 6 days/week at 75% maximal inspiratory pressure · midlife/older adults (50-79 y) with systolic BP >=120 mmHg · n = 36 · rct · Craighead DH, et al. J Am Heart Assoc, 2021 PMID 34184544
↑ 3.2 % (1.7 to 4.6) Aerobic training in prehypertension/hypertension · Within-group change in FMD after 8 weeks of cycling
8 wk · 40 min, twice/week, 50-75% heart rate reserve · prehypertension or hypertension · n = 42 · rct · Pedralli ML, et al. Sci Rep, 2020 PMID 32376984
↑ 4 % (2.1 to 5.7) Resistance training in prehypertension/hypertension · Within-group change in FMD after 8 weeks of resistance exercise
8 wk · 6 exercises, 4 x 12 repetitions, 60% maximum strength, twice/week · prehypertension or hypertension · n = 42 · rct · Pedralli ML, et al. Sci Rep, 2020 PMID 32376984

Reactive hyperaemia index EndoPAT reactive hyperaemia index (index) · physical parameter

0 3 4

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (0)

no quantified finding yet

Link to healthspan (3)

↓ ratio 0.85 (0.78 to 0.93) RHI and cardiovascular events → cardiovascular events and all-cause mortality · Pooled RR per 0.1 increase in reactive hyperaemia index (3 studies); outcome CV events and all-cause mortality
mixed populations · meta analysis · Xu Y, et al. Eur Heart J Cardiovasc Imaging, 2014 PMID 24399339
↕ ratio 1.24 (0.8 to 1.93) LnRHI and MACE in older NSTEACS → major adverse cardiovascular events · Cox HR for MACE, not significant (mortality HR 1.49, 95% CI 0.86-2.59); scaling of LnRHI not stated in the abstract
patients aged >=75 y with non-ST elevation ACS · n = 214 · prospective cohort · Dirjayanto VJ, et al. Coron Artery Dis, 2024 PMID 38436050
↓ ratio 10.95 (1 to 119.91) Peripheral endothelial dysfunction (RHI <1.67) and MACE in diabetes → major adverse cardiovascular events · Adjusted HR for 3-point MACE with RHI <1.67 vs >=1.67 (secondary composite outcome HR 4.12, 95% CI 1.37-12.41)
diabetic patients with albuminuria · n = 149 · prospective cohort · Koo BK, et al. Cardiovasc Diabetol, 2020 PMID 32534580

Remedy and magnitude (4)

↑ SMD 0.65 (0.33 to 0.96) Exercise training in cancer survivors · Aerobic exercise training, pooled SMD for vascular endothelial function vs control (FMD in 3 trials, RHI in 1)
breast and prostate cancer survivors · n = 163 · meta analysis · Beaudry RI, et al. Integr Cancer Ther, 2018 PMID 29390904
↑ 0.11 LnRHI Citrulline supplementation · Change in LnRHI 0.11 +/- 0.16 with citrulline vs -0.08 +/- 0.24 with placebo, p<0.05 (crossover)
4 wk · 6 g/day · middle-aged and older adults (53-72 y) with type 2 diabetes · n = 16 · rct · Figueroa A, et al. Nutrients, 2025 PMID 40944179
↑ 0.2 RHI Catechins, single 500 mg dose · Change in RHI vs placebo (EndoPAT) after a single dose, p=0.04
500 mg catechins, single dose · healthy subjects · n = 24 · rct · Fuchs D, et al. Nutrients, 2014 PMID 25514559
↑ 0.28 RHI Theaflavins, single 300 mg dose · Change in RHI vs placebo (EndoPAT) after a single dose; 500 mg gave 0.19 (p=0.06), lower doses had no effect
300 mg theaflavins, single dose · healthy subjects · n = 24 · rct · Fuchs D, et al. Nutrients, 2014 PMID 25514559

Carotid intima-media thickness Common-carotid IMT (mm) · physical parameter on the landscape

6 2 7

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, Peto et al. 2017 (MortalityPredictors.org) anchor cohort (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (6)

↑ 0.89 mm Healthy centenarians vs younger adults · Carotid IMT 0.89 +/- 0.09 mm in centenarians (101 +/- 1 y) vs 0.56 +/- 0.18 mm in controls (41 +/- 14 y), P<0.001; effect value is the centenarian IMT
ages 101 +/- 1 y vs 41 +/- 14 y · healthy centenarians vs younger controls · cross sectional · Buscemi C, et al. Exp Gerontol, 2024 PMID 38728795
↑ 5.8 um per year Healthy Chinese men, cIMT increase per year · Rate of carotid IMT increase with age by RF ultrasound, men 18-79 y
ages 18-79 y · healthy Han Chinese adults · n = 3,053 · normative study · Xing C, et al. Chin Med J, 2024 PMID 38958034
↑ 5.5 um per year Healthy Chinese women, cIMT increase per year · Rate of carotid IMT increase with age by RF ultrasound, women 18-79 y
ages 18-79 y · healthy Han Chinese adults · n = 3,053 · normative study · Xing C, et al. Chin Med J, 2024 PMID 38958034
↑ 0.006 mm per year Unaffected siblings, 20-year IMT progression · Mean progression of carotid IMT over the 20-year follow-up in unaffected siblings of FH patients
unaffected siblings of patients with familial hypercholesterolaemia · n = 77 · prospective cohort · Luirink IK, et al. N Engl J Med, 2019 PMID 31618540
↑ 0.061 mm Median, ages 40–59 vs 20–39 catalogue · 0.6992 → 0.76 (+9%)
ages 40–59 vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 10,040 · cross sectional · Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study. J Am Heart Assoc. 2023;12(14):e029656. PMID 37345827
↑ 0.129 mm Median, ages 60+ vs 20–39 catalogue · 0.6992 → 0.8284 (+18%)
ages 60+ vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 10,040 · cross sectional · Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study. J Am Heart Assoc. 2023;12(14):e029656. PMID 37345827

Link to healthspan (2)

↕ ratio 0.92 (0.53 to 1.59) CIMT and MACE in older NSTEACS → major adverse cardiovascular events · Cox HR for MACE, not significant; scaling of CIMT not stated in the abstract
patients aged >=75 y with non-ST elevation ACS · n = 190 · prospective cohort · Dirjayanto VJ, et al. Coron Artery Dis, 2024 PMID 38436050
ratio 1.54 (1.32 to 1.79) Cao JJ, Arnold AM, Manolio TA, Polak JF, Psaty BM, Hirsch CH, Kuller LH, Cushman M. Associ catalogue → mortality · highest vs lowest tertile
general · n = 5,020 · prospective cohort · Cao JJ, Arnold AM, Manolio TA, Polak JF, Psaty BM, Hirsch CH, Kuller LH, Cushman M. Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study. Circulation. 2007;116(1):32-38. PMID 17576871

Remedy and magnitude (7)

↓ -0.02 mm (-0.04 to -0.01) Aerobic exercise · WMD in cIMT vs control, aerobic subgroup
adults · n = 1,370 · meta analysis · Wang Y, et al. J Phys Act Health, 2022 PMID 36257606
↓ -0.02 mm (-0.03 to -0.01) Exercise training in adults · WMD in cIMT vs control, 26 studies
adults · n = 1,370 · meta analysis · Wang Y, et al. J Phys Act Health, 2022 PMID 36257606
↓ -0.049 mm (-0.095 to -0.004) Metformin · WMD in CIMT vs control, 9 RCTs
mixed populations in randomised trials · n = 1,087 · meta analysis · Chen Y, et al. Eur J Pharmacol, 2020 PMID 32763300
↓ -0.084 mm (-0.145 to -0.024) Metformin, duration >=12 months · Stratified WMD for intervention lasting >=12 months (dose <=1500 mg/day gave WMD -0.081, -0.132 to -0.029)
mixed populations in randomised trials · n = 1,087 · meta analysis · Chen Y, et al. Eur J Pharmacol, 2020 PMID 32763300
↓ 0.004 mm per year Oral estradiol started <6 years after menopause · Mean CIMT progression 0.0044 mm per year with estradiol vs 0.0078 mm per year with placebo, P=0.008
healthy postmenopausal women <6 years past menopause · n = 643 · rct · Hodis HN, et al. N Engl J Med, 2016 PMID 27028912
↓ -0.003 mm Oral estradiol 1 mg/day started <6 years after menopause (ELITE) catalogue · vs placebo
1.0 mg daily, 5 years · healthy postmenopausal women <6 years past menopause (ELITE; 643 women in both strata) · rct · Hodis HN, et al. The New England journal of medicine. 2016. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. PMID 27028912
↓ -1.1% Two-year weight-loss diet (low-fat, Mediterranean or low-carbohydrate; DIRECT-Carotid) catalogue · vs baseline
2 years · 140 adults with complete carotid imaging (mean age 51, BMI 30, 88% men) · n = 140 · rct · Shai I, et al. Circulation. 2010. Dietary intervention to reverse carotid atherosclerosis. PMID 20194883

Coronary artery calcium Agatston score (Agatston units) · physical parameter on the landscape

4 4 4

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, Peto et al. 2017 (MortalityPredictors.org) anchor cohort (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (4)

↑ 28.5% per year Annual CAC progression in men · Rate of mean CAC progression per year in initially healthy adults (mean age 50.2 y), independent of physical activity
ages adults 40+ y, mean baseline age 50.2 y (men) · apparently healthy men and women, Cooper Clinic · n = 8,771 · prospective cohort · Shuval K, et al. JAMA Cardiol, 2024 PMID 38748444
↑ 32.1% per year Annual CAC progression in women · Rate of mean CAC progression per year in initially healthy adults (mean age 51.1 y), independent of physical activity
ages adults 40+ y, mean baseline age 51.1 y (women) · apparently healthy men and women, Cooper Clinic · n = 8,771 · prospective cohort · Shuval K, et al. JAMA Cardiol, 2024 PMID 38748444
↑ 5.2 Agatston units Median, ages 40–59 vs 20–39 catalogue · 59.8 → 65 (+9%)
ages 40–59 vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 19,430 · cross sectional · Multi-Ethnic Study of Atherosclerosis (MESA) CAC Score Reference Values tool — demographic-specific coronary artery calcium score percentile distributions.
↑ 11.05 Agatston units Median, ages 60+ vs 20–39 catalogue · 59.8 → 70.85 (+18%)
ages 60+ vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 19,430 · cross sectional · Multi-Ethnic Study of Atherosclerosis (MESA) CAC Score Reference Values tool — demographic-specific coronary artery calcium score percentile distributions.

Link to healthspan (4)

↑ ratio 5.47 (2.59 to 11.53) CAC >=10 vs <10 in type 2 diabetes → all-cause mortality or cardiovascular events · Pooled RR for all-cause mortality or cardiovascular events (CV events alone: RR 9.22, 95% CI 2.73-31.07)
type 2 diabetes · n = 6,521 · meta analysis · Kramer CK, et al. BMJ, 2013 PMID 23529983
↑ ratio 0.08 (0.02 to 0.3) CAC 0 vs >=400 in stable chest pain → major adverse cardiovascular events · HR for MACE with CAC 0 vs CAC >=400 (CAC 1-399: HR 0.27, 95% CI 0.13-0.59)
stable chest pain referred for invasive angiography · n = 1,749 · prospective cohort · Biavati F, et al. Radiology, 2024 PMID 38441097
↑ ratio 1.9 (1.51 to 2.38) ln(CAC+1) and incident CHD in younger adults → incident coronary heart disease · HR per SD of ln(CAC+1), median follow-up 9.2 years, mean age 44.4 y
Dallas Heart Study, no baseline CVD or diabetes · n = 2,084 · prospective cohort · Paixao AR, et al. JACC Cardiovasc Imaging, 2015 PMID 26476504
ratio 2.67 (2.29 to 3.11) Valenti V, Hartaigh BO, Heo R, Cho I, Schulman-Marcus J, Gransar H, Truong QA, Shaw LJ, Kn catalogue → mortality · highest vs lowest quartile
general · n = 9,715 · prospective cohort · Valenti V, Hartaigh BO, Heo R, Cho I, Schulman-Marcus J, Gransar H, Truong QA, Shaw LJ, Knapper J, Kelkar AA, Sandesara P, Lin FY, Sciarretta S, Chang HJ, Callister TQ, Min JK. A 15-Year Warranty Period for Asymptomatic Individuals Without Coronary Artery Calcium: A Prospective Follow-Up of 9,715 Individuals. JACC Cardiovasc Imaging. 2015;8(8):900-909. PMID 26189116

Remedy and magnitude (4)

↑ 8.52% Strict phosphate control in dialysis · Median percentage change in CAC score over 12 months, strict phosphate target (3.5-4.5 mg/dl) vs 21.8% with standard target (5.0-6.0 mg/dl), P=0.006
sucroferric oxyhydroxide or lanthanum carbonate to phosphate target 3.5-4.5 mg/dl · adults on maintenance dialysis · n = 160 · rct · Isaka Y, et al. J Am Soc Nephrol, 2021 PMID 33547218
↓ -8.9 Agatston units Calcium carbonate 1000 mg + vitamin D3 400 IU daily, 7 years (WHI) catalogue · vs placebo
1000.0 mg elemental calcium daily, 7 years · 754 postmenopausal women aged 50-59 at randomisation (WHI CaD/estrogen trial substudy) · n = 754 · rct · Manson JE, et al. Menopause (New York, N.Y.). 2010. Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative. PMID 20551849
↓ -20 Agatston units Menaquinone-7 (vitamin K2) 360 ug/day, 2 years (VitaK-CAC) catalogue · vs placebo
360.0 ug daily, 2 years · 180 patients with symptomatic CAD and baseline CAC 50-400 AU (median age ~60) · n = 180 · rct · Vossen LM, et al. JAMA cardiology. 2026. Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial. PMID 42268593
↓ -13.5% Cinacalcet plus low-dose vitamin D in haemodialysis patients with secondary hyperparathyroidism (ADVANCE) catalogue · vs active comparator (vitamin D sterols alone)
52 wk · haemodialysis patients with secondary hyperparathyroidism (post-hoc: 70 protocol-adherent cinacalcet vs 120 controls) · n = 190 · rct · Ureña-Torres PA, et al. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Associ PMID 23028103

Ankle-brachial index ABI (ratio) · physical parameter on the landscape

2 3 3

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, Peto et al. 2017 (MortalityPredictors.org) anchor cohort (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (2)

↑ 0.082 ratio Median, ages 40–59 vs 20–39 catalogue · 0.9476 → 1.03 (+9%)
ages 40–59 vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 14,916 · cross sectional · Oguanobi NI, Onwubere BJ, Ibegbulam OG, Ike SO, Ejim EC, Agwu O. An evaluation of ankle-brachial blood pressure index in adult Nigerians with sickle cell anaemia (control group without PAD). Cardiovasc J Afr. 2012;23(4):184-187. PMID 22331250
↑ 0.175 ratio Median, ages 60+ vs 20–39 catalogue · 0.9476 → 1.123 (+18%)
ages 60+ vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 14,916 · cross sectional · Oguanobi NI, Onwubere BJ, Ibegbulam OG, Ike SO, Ejim EC, Agwu O. An evaluation of ankle-brachial blood pressure index in adult Nigerians with sickle cell anaemia (control group without PAD). Cardiovasc J Afr. 2012;23(4):184-187. PMID 22331250

Link to healthspan (3)

↓ ratio 2.74 (2.03 to 3.68) ABI <0.90 and all-cause mortality → all-cause mortality · Pooled OR for ABI <0.90 vs >=0.90, 10 studies
mixed populations · n = 22,705 · meta analysis · Qu B, et al. Cell Biochem Biophys, 2015 PMID 27352355
↓ ratio 3.23 (1.98 to 5.29) ABI <0.90 and cardiovascular mortality → cardiovascular mortality · Pooled OR for ABI <0.90 vs >=0.90 (non-cardiovascular mortality OR 2.23, 95% CI 1.40-3.55)
mixed populations · n = 22,705 · meta analysis · Qu B, et al. Cell Biochem Biophys, 2015 PMID 27352355
ratio 1.9 (1.3 to 2.8) Pande RL, Perlstein TS, Beckman JA, Creager MA. Secondary prevention and mortality in peri catalogue → mortality · highest vs lowest quartile
general · n = 7,458 · prospective cohort · Pande RL, Perlstein TS, Beckman JA, Creager MA. Secondary prevention and mortality in peripheral artery disease: National Health and Nutrition Examination Study, 1999 to 2004. Circulation. 2011;124(1):17-23. PMID 21690489

Remedy and magnitude (3)

↑ 0.14 ABI score (0.08 to 0.19) Buerger-Allen exercise in diabetes · Pooled MD in ABI scores, 4 RCTs and 6 quasi-experimental studies
diabetes mellitus · meta analysis · Thakur A, et al. Diabetes Metab Syndr, 2022 PMID 35085917
↑ 0.09 ABI units (0.08 to 0.09) Propionyl-L-carnitine in intermittent claudication · Mean difference in improvement in ABI vs placebo, 4 studies
1-2 g/day oral or intravenous · stable intermittent claudication, Fontaine stage II · n = 369 · meta analysis · Kamoen V, et al. Cochrane Database Syst Rev, 2021 PMID 34954832
↑ 0.09 ratio (0.08 to 0.09) Propionyl-L-carnitine for intermittent claudication catalogue · vs placebo
2.0 g daily · adults with intermittent claudication (4 studies) · n = 369 · meta analysis · Kamoen V, Vander Stichele R, Campens L, et al. Cochrane Database Syst Rev. 2021. PMID 34954832

Augmentation index Central augmentation index / wave reflection (%) · physical parameter

2 2 1

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↑ ratio 1.56 Radial augmentation index, men in their 70s vs 20s · Radial AI 1.56 times higher in men in their 70s than in their 20s (53.2% to 83.0%)
ages 20s vs 70s · adults without cardiovascular disease, men · n = 632 · cross sectional · Kohara K, et al. Am J Hypertens. 2005. PMID 15683726
↑ ratio 1.49 Radial augmentation index, women in their 70s vs 20s · Radial AI 1.49 times higher in women in their 70s than in their 20s (64.6% to 96.4%)
ages 20s vs 70s · adults without cardiovascular disease, women · n = 632 · cross sectional · Kohara K, et al. Am J Hypertens. 2005. PMID 15683726

Link to healthspan (2)

↑ ratio 1.51 (1.23 to 1.86) AIx and all-cause mortality in end-stage renal failure → all-cause mortality · Adjusted risk ratio for each 10% increase in carotid augmentation index
end-stage renal failure patients · n = 180 · prospective cohort · London GM, et al. Hypertension, 2001 PMID 11566918
↑ ratio 1.48 (1.16 to 1.9) AIx and cardiovascular mortality in end-stage renal failure → cardiovascular mortality · Adjusted risk ratio for each 10% increase in carotid augmentation index
end-stage renal failure patients · n = 180 · prospective cohort · London GM, et al. Hypertension, 2001 PMID 11566918

Remedy and magnitude (1)

↓ -2.63 % (-5.25 to -0.02) Aerobic exercise training · Pooled WMD in AIx vs control, RCTs of >=4 weeks (resistance and combined exercise had no significant effect)
adults >=18 y · n = 1,627 · meta analysis · Ashor AW, et al. PLoS One, 2014 PMID 25333969

Cerebral blood flow Cerebral blood flow / cerebrovascular reactivity (mL/100g/min; %/mmHg) · physical parameter

3 2 3

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Total cerebral blood flow (phase-contrast MRA), healthy adults, -2.6 mL/minute per year.

Change with age (3)

↓ -2.6 mL/minute per year Total cerebral blood flow (phase-contrast MRA), healthy adults · Total cerebral blood flow declined with age at 2.6 mL/minute per year
ages 18-84 y · healthy adult volunteers · n = 325 · normative study · Amin-Hanjani S, et al. J Cereb Blood Flow Metab. 2015. PMID 25388677
↓ -0.45% per year Grey-matter perfusion (CASL MRI), healthy adults · Grey-matter perfusion decreased 0.45% per year; GM/WM perfusion ratio decreased 0.79% per year
ages adult range of the 34 subjects · healthy adults · n = 34 · normative study · Parkes LM, et al. Magn Reson Med. 2004. PMID 15065246
↓ -0.3% per year (-0.5 to -0.3) Cerebral blood flow in healthy ageing (review of 33 studies) · Cerebral blood flow decreases 0.3-0.5% per year in healthy ageing (2-5% per year in Alzheimer's disease); value is the lower bound of the stated range
ages healthy ageing · healthy older adults (33 included studies) · review · Graff BJ, et al. Cerebrovasc Dis. 2023. PMID 35640565

Link to healthspan (2)

↓ ratio 1.54 (1.11 to 2.14) Hypoperfusion with severe white matter hyperintensities and dementia → dementia · HR for dementia with lower perfusion in participants with severe white matter hyperintensities
Rotterdam Study participants without dementia · n = 4,759 · prospective cohort · Wolters FJ, et al. Circulation, 2017 PMID 28588075
↓ ratio 1.31 (1.07 to 1.61) Lower cerebral perfusion and incident dementia → dementia · Adjusted HR for dementia per SD decrease in cerebral perfusion (2D phase-contrast MRI), median follow-up 6.9 years
Rotterdam Study participants without dementia, median age 61.3 y · n = 4,759 · prospective cohort · Wolters FJ, et al. Circulation, 2017 PMID 28588075

Remedy and magnitude (3)

↑ 1.82 mL/100 g per minute (0.5 to 3.15) Sildenafil: perfusion in white matter hyperintensities · Change in ASL perfusion within WMH vs placebo (crossover); normal-appearing white matter 2.12 (0.66-3.6) mL/100 g per minute
3 wk · 50 mg three times daily · cerebral small vessel disease after non-embolic cerebrovascular event, median age 70 y · n = 65 · rct · Webb AJS, et al. Circ Res, 2024 PMID 38832504
↑ 0.83 cm/s per mm Hg (0.23 to 1.42) Sildenafil: transcranial ultrasound cerebrovascular reactivity · Change in CVR (transcranial ultrasound, during 4% and 6% CO2 inhalation) vs placebo
3 wk · 50 mg three times daily · cerebral small vessel disease after non-embolic cerebrovascular event, median age 70 y · n = 65 · rct · Webb AJS, et al. Circ Res, 2024 PMID 38832504
↑ 9.8% Tadalafil single dose: perfusion within WMH · Change in subcortical CBF by arterial spin labelling, largest within white matter hyperintensities, not significant (P=.0960)
20 mg single dose · older people with symptomatic small vessel disease · n = 55 · rct · Pauls MMH, et al. Alzheimers Dement, 2022 PMID 35135037

Autonomic

Vagal tone HRV RMSSD / high-frequency power (ms; ms2) · capacity on the landscape

2 2 4

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Catalogue median by age band, Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hou (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (2)

↓ -20 ms (24-h SDNN) Median, ages 40–59 vs 20–39 catalogue · 157 → 137 (-13%)
ages 40–59 vs 20–39 · Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hou · n = 520 · cross sectional · Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol. 1998;31(3):593-601. PMID 9502641
↓ -45 ms (24-h SDNN) Median, ages 60+ vs 20–39 catalogue · 157 → 112 (-29%)
ages 60+ vs 20–39 · Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hou · n = 520 · cross sectional · Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol. 1998;31(3):593-601. PMID 9502641

Link to healthspan (2)

↑ ratio 1.56 (1.32 to 1.85) All-cause mortality, lowest quartile of 5-min RMSSD → all-cause mortality · Combined HR for lowest RMSSD quartile vs other quartiles (sub-analysis); 32 studies plus 2 IPD datasets
healthy and patient populations, 37 samples · n = 38,008 · meta analysis · Jarczok MN, et al. Neurosci Biobehav Rev. 2022. PMID 36243195
ratio 1.38 (1.13 to 1.7) Framingham Heart Study, original cohort attendees of the 18th biennial exam, n=736, mean a catalogue → mortality · per 1 SD
general · prospective cohort · Tsuji H, Venditti FJ Jr, Manders ES, Evans JC, Larson MG, Feldman CL, Levy D. Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation. 1994;90(2):878-883. PMID 8044959

Remedy and magnitude (4)

↑ SMD 0.58 (-0.16 to 0.99) Exercise training in type 2 diabetes (HF power) · Effect size for change in high-frequency power after exercise training; CI crosses zero
type 2 diabetes patients · n = 523 · meta analysis · Picard M, et al. PLoS One. 2021. PMID 33999947
↑ SMD 0.62 (0.28 to 0.95) Exercise training in type 2 diabetes (RMSSD) · Effect size for change in RMSSD after exercise training; 21 studies, 472 trained vs 151 controls (no change in controls)
endurance (14 studies), resistance (2), combined (4), HIIT (4) · type 2 diabetes patients · n = 523 · meta analysis · Picard M, et al. PLoS One. 2021. PMID 33999947
↑ SMD 0.58 Endurance training producing performance gains, athletes (resting RMSSD) · SMD for change in resting RMSSD in studies where training increased performance; 24 studies in meta-analysis
endurance-trained athletes · meta analysis · Bellenger CR, et al. Sports Med. 2016. PMID 26888648
↑ 0.4 ln ms2 (0.2 to 0.6) Diet, weight management and exercise in resistant hypertension (HF-HRV) · Change in high-frequency HRV in the C-LIFE arm (ln ms2); SEPA control arm -0.2 (-0.5 to 0.1); P < 0.001 between groups
4-month centre-based programme (dietary counselling, behavioural weight management, exercise) · patients with resistant hypertension, mean age 63 · n = 140 · rct · Blumenthal JA, et al. Circulation. 2021. PMID 34565172

Baroreflex sensitivity Baroreflex sensitivity (ms/mmHg) · capacity

3 4 1

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Spontaneous BRS, regression on age (healthy working population), -0.03 lnBRS (natural log of ms/mmHg) per year.

Change with age (3)

↓ -40% Cardiovagal BRS, older vs young endurance-trained men · Cardiovagal BRS approximately 40% lower in older than young endurance-trained men
ages young (27 y) vs older (63 y) · healthy endurance-trained men · n = 19 · cross sectional · mechanism: lower carotid artery compliance (stated association) · Monahan KD, et al. Circulation. 2001. PMID 11581140
↓ -65% Cardiovagal BRS, older vs young sedentary men · Cardiovagal BRS (Oxford technique) approximately 65% lower in older than young sedentary men
ages young (28 y) vs older (65 y) · healthy sedentary men · n = 18 · cross sectional · mechanism: lower carotid artery compliance (stated association) · Monahan KD, et al. Circulation. 2001. PMID 11581140
↓ -0.03 lnBRS (natural log of ms/mmHg) per year Spontaneous BRS, regression on age (healthy working population) · lnBRS = 3.24 - 0.03 x age (r2 = 0.23), sequence technique, both sexes
ages 18-60 y · healthy volunteers 18-60 y · n = 1,134 · normative study · Kardos A, et al. Hypertension. 2001. PMID 11244017

Link to healthspan (4)

↑ ratio 2.65 (1.4 to 5.59) Memory impairment, severe autonomic dysregulation (BRS <=3) vs normal (>6) → memory impairment · Adjusted OR for memory impairment; moderate dysregulation (3 < BRS <= 6) OR 1.82 (1.13-3.17)
healthy young-elderly, aged 66.9 +/- 0.9, PROOF cohort · n = 916 · cross sectional · Saint Martin M, et al. J Am Geriatr Soc. 2013. PMID 24279643
↑ ratio 1.76 (1.32 to 2.35) All-cause mortality, bottom vs top quintile of cardiac BRS (untreated) → all-cause mortality · Adjusted HR for reduced BRS, participants not taking antihypertensive medication
community-dwelling older adults, mean age 71.0 · n = 1,819 · prospective cohort · Ma Y, et al. Hypertension. 2025. PMID 39670317
↑ ratio 1.6 (1.07 to 2.4) Incident dementia, bottom vs top quintile of cardiac BRS (untreated) → dementia · Adjusted HR, participants not taking antihypertensive medication; median follow-up 14.8 years, Rotterdam Study
community-dwelling older adults, mean age 71.0 · n = 1,819 · prospective cohort · Ma Y, et al. Hypertension. 2025. PMID 39670317
↑ ratio 2.76 (1.36 to 5.63) Cardiac death / ICD shock / HF hospitalisation, reduced BRS in chronic heart failure → cardiac death, ICD shock or heart failure hospitalisation · Adjusted HR for decreased BRS (SD method) for the composite endpoint; median follow-up 50 months
outpatients with chronic HF, LVEF <=49%, 94% on beta blockers · n = 425 · prospective cohort · Giannoni A, et al. JACC Heart Fail. 2022. PMID 36049816

Remedy and magnitude (1)

↑ 2.3 ms/mm Hg (1.3 to 3.3) Diet, weight management and exercise in resistant hypertension · Change in resting BRS in the C-LIFE arm; SEPA control arm -1.1 ms/mm Hg (-2.5 to 0.3); P < 0.001 between groups
4-month centre-based programme (dietary counselling, behavioural weight management, exercise) · patients with resistant hypertension, mean age 63 · n = 140 · rct · Blumenthal JA, et al. Circulation. 2021. PMID 34565172

Orthostatic tolerance Orthostatic BP drop (mmHg) · capacity

0 4 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (0)

no quantified finding yet

Link to healthspan (4)

↑ ratio 1.73 (1.5 to 1.99) Falls in older adults, orthostatic hypotension → falls · Pooled unadjusted OR for falls with orthostatic hypotension; 50 studies in meta-analysis
adults with mean/median age >=65 · n = 49,164 · meta analysis · Mol A, et al. J Am Med Dir Assoc. 2019. PMID 30583909
↑ ratio 1.37 (1.01 to 1.88) Incident dementia, systolic orthostatic hypotension → dementia · Adjusted HR for systolic OHYPO (fall >=15 mm Hg systolic on >=1/3 of visits over 5-year baseline); 12-year follow-up, Health ABC
older adults, mean age 73 · n = 2,131 · prospective cohort · Rouch L, et al. Neurology. 2020. PMID 32690802
↑ ratio 1.61 (1.17 to 2.2) New-onset atrial fibrillation, orthostatic hypotension (Framingham) → atrial fibrillation · Multivariable-adjusted HR for OH (>=20 mm Hg systolic or >=10 mm Hg diastolic drop after 2 min standing); 10-year follow-up
Framingham Original cohort, mean age 71.7 · n = 1,736 · prospective cohort · Ko D, et al. Am J Cardiol. 2018. PMID 29290367
↑ ratio 1.05 (1.01 to 1.1) Low-energy fractures per 10 mmHg orthostatic systolic BP decrease → low-energy fractures · Adjusted risk per 10 mmHg orthostatic decrease in systolic BP at baseline (5% increased risk); 25-year follow-up, Malmo Preventive Project
middle-aged general population · n = 33,000 · prospective cohort · Hamrefors V, et al. PLoS One. 2016. PMID 27124658

Remedy and magnitude (3)

-2.07 mm Hg (-4.2 to 0.06) Pyridostigmine alone: systolic orthostatic drop · Mean difference in systolic orthostatic drop vs placebo (4 RCTs)
orthostatic hypotension (mostly neurogenic) · meta analysis · Pavic NV, et al. Open Heart. 2025;12(1). PMID 40132893
↓ -6.74 mm Hg (-13.15 to -0.33) Pyridostigmine plus midodrine: smaller systolic orthostatic drop · Mean difference in systolic orthostatic drop vs placebo (2 RCTs)
orthostatic hypotension (mostly neurogenic) · meta analysis · Pavic NV, et al. Open Heart. 2025;12(1). PMID 40132893
-1.7 mmHg Midodrine: supine-to-standing change in mean arterial pressure vs placebo · Pooled mean change in MAP from supine to standing, midodrine vs placebo
orthostatic hypotension, mean age 53 · n = 325 · meta analysis · Parsaik AK, et al. J Gen Intern Med. 2013;28(11):1496-503. PMID 23775146

Brain structure

Hippocampal volume Hippocampal volume (MRI) (mm3; %) · physical parameter

3 1 1

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Hippocampal atrophy, healthy adults, studies with mean age 55-70 y, -0.98% per year (-1.7 to -0.27).

Change with age (3)

↓ -0.98% per year (-1.7 to -0.27) Hippocampal atrophy, healthy adults, studies with mean age 55-70 y · 0.98% per year (CI 0.27-1.70) for studies with mean age 55 to <70 y (n=426)
ages 55-<70 y (study mean age) · cognitively healthy adults · n = 3,422 · meta analysis · Fraser MA, et al. Neuroimage. 2015. PMID 25800208
↓ -0.38% per year (-0.62 to -0.14) Hippocampal atrophy, healthy adults, studies with mean age <55 y · Meta-analysis of 28 longitudinal MRI studies (11,735 person-years); 0.38% per year (CI 0.14-0.62) for studies with mean age <55 y (n=413)
ages <55 y (study mean age) · cognitively healthy adults · n = 3,422 · meta analysis · Fraser MA, et al. Neuroimage. 2015. PMID 25800208
↓ -1.12% per year (-1.38 to -0.86) Hippocampal atrophy, healthy adults, studies with mean age >=70 y · 1.12% per year (CI 0.86-1.38) for studies with mean age >=70 y (n=2583); whole-sample mean 0.85% per year (0.63-1.07); atrophy rate rises 0.0263% per year of age
ages >=70 y (study mean age) · cognitively healthy adults · n = 3,422 · meta analysis · Fraser MA, et al. Neuroimage. 2015. PMID 25800208

Link to healthspan (1)

↑ ratio 3 (2 to 4.6) Smaller hippocampal volume and incident dementia, cognitively intact elderly → dementia · Rotterdam Scan Study, 3043 person-years; age-, sex- and education-adjusted HR per 1-SD decrease in volume
community-dwelling adults 60-90 y free of dementia · n = 511 · prospective cohort · den Heijer T, et al. Arch Gen Psychiatry. 2006. PMID 16389197

Remedy and magnitude (1)

↑ 2% Aerobic exercise training · Aerobic exercise training increased hippocampal volume by 2% versus a control group in which volume declined; abstract states this effectively reverses 1 to 2 y of age-related loss
older adults · n = 120 · rct · Erickson KI, et al. Proc Natl Acad Sci U S A. 2011. PMID 21282661

Brain volume Whole-brain volume / atrophy rate (%/year; mL) · physical parameter

3 2 3

Trajectory with age: default, and given an intervention

Intervention starts at age 49

Default (no intervention)Given the selected intervention

Default: Whole-brain volume loss, cognitively normal adults in their 40s, -0.24% per year.

Change with age (3)

↓ -0.52% per year Brain parenchyma volume loss per year, physiological ageing (age 70) · Age-volume curves in healthy adults: brain parenchyma volume loss per year rises from 0.20% at age 35 to 0.52% at age 70 (MPCH cohort; consistent in OASIS)
ages 35-70 y (value at 70 y) · healthy adults, two single-scanner cohorts (n=248 and n=316) · n = 564 · cross sectional · Schippling S, et al. J Neurol. 2017. PMID 28054131
↓ -0.24% per year Whole-brain volume loss, cognitively normal adults in their 40s · Annual percentage change in whole-brain volume from serial MRI (7915 scans, up to 15 y follow-up); decline 0.24% per year in the 40s
ages 40-49 y · cognitively normal Japanese adults (health screening cohort) · n = 653 · prospective cohort · Fujita S, et al. Brain Commun. 2026. PMID 42765092
↓ -0.44% per year Whole-brain volume loss, cognitively normal adults in their 70s · Whole-brain volume decline accelerated to 0.44% per year in the 70s (from 0.24% per year in the 40s)
ages 70-79 y · cognitively normal Japanese adults (health screening cohort) · n = 653 · prospective cohort · Fujita S, et al. Brain Commun. 2026. PMID 42765092

Link to healthspan (2)

↓ ratio 0.71 (0.65 to 0.78) Higher total brain volume and all-cause mortality → all-cause mortality · Total brain volume (brain tissue / intracranial volume) and mortality over mean 7.2 y (647 deaths), adjusted for demographics, CV risk factors and cerebrovascular disease; increment not stated in the abstract
nondemented stroke-free older adults, AGES-Reykjavik · n = 3,543 · prospective cohort · Van Elderen SS, et al. J Gerontol A Biol Sci Med Sci. 2016. PMID 25359930
↑ ratio 1.1 (1.02 to 1.19) Lower brain parenchymal fraction and conversion MCI to dementia → dementia (conversion from MCI) · Adjusted HR 1.10 per 1% decrease in brain parenchymal fraction for conversion to dementia; HR 1.16 (1.08-1.24) per 1% decrease for AD dementia
volunteers with normal cognition (67) or MCI (156) · n = 223 · prospective cohort · Smith EE, et al. Arch Neurol. 2008. PMID 18195145

Remedy and magnitude (3)

↑ SMD 0.1 Physical exercise and brain volume (59 RCTs) · Multilevel meta-analysis of 59 RCTs; exercise vs control, Hedges g = 0.10
mixed RCT populations · n = 5,099 · meta analysis · Li G, et al. Appl Psychol Health Well Being. 2025. PMID 41022634
SMD 0.012 (-0.055 to 0.078) Exercise interventions, older adults: no effect on brain volume · 14 RCTs (69 effects), healthy older adults and MCI; exercise vs control, Hedges g
healthy older adults and older adults with MCI (60+) · meta analysis · Gogniat MA, et al. Neurobiol Aging. 2021. PMID 33640675
↓ -53% B vitamins (folic acid, B12, B6): slower brain atrophy rate · Mean atrophy rate 0.76%/y (0.63-0.90) with B vitamins vs 1.08%/y (0.94-1.22) placebo (P=0.001); value is the stated 53% lower atrophy rate in participants with homocysteine >13 umol/L
104 wk · folic acid 0.8 mg/d, vitamin B12 0.5 mg/d, vitamin B6 20 mg/d for 24 months · adults >70 y with mild cognitive impairment (VITACOG) · n = 168 · rct · mechanism: homocysteine lowering · Smith AD, et al. PLoS One. 2010. PMID 20838622

White-matter hyperintensities WMH volume (mL) · physical parameter

1 3 2

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: WMH accrual in community-dwelling adults in their 80s, 3.3 ml per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (1)

↑ 3.3 ml per year WMH accrual in community-dwelling adults in their 80s · Total WMH volume increased 3.3 +/- 3.5 ml/year over 2 years, mainly through enlargement
ages baseline 82 +/- 4 y · community-dwelling older adults · n = 77 · prospective cohort · Moscufo N, et al. Age (Dordr). 2012. PMID 21505765

Link to healthspan (3)

↑ ratio 2 (1.69 to 2.36) Extensive WMH burden and death → mortality · HR for all-cause death with extensive white matter hyperintensity burden vs not (meta-analysis)
community-dwelling older persons, prospective cohorts · n = 14,529 · meta analysis · Debette S, et al. JAMA Neurol. 2019. PMID 30422209
↑ ratio 1.84 (1.4 to 2.43) Extensive WMH burden and incident dementia → dementia · HR for incident dementia with extensive white matter hyperintensity burden vs not (meta-analysis)
community-dwelling older persons, prospective cohorts · n = 14,529 · meta analysis · Debette S, et al. JAMA Neurol. 2019. PMID 30422209
↑ ratio 2.45 (1.93 to 3.12) Extensive WMH burden and incident stroke → stroke · HR for incident stroke with extensive white matter hyperintensity burden vs not (meta-analysis of prospective cohorts)
community-dwelling older persons, prospective cohorts · n = 14,529 · meta analysis · Debette S, et al. JAMA Neurol. 2019. PMID 30422209

Remedy and magnitude (2)

↓ -75% Intensive SBP control, age 65 y or younger · Intensive (<120 mm Hg) vs standard (<140 mm Hg) systolic BP treatment: WMH volume progression reduced by 75% (change -0.19 asinh-transformed units, 95% CI -0.28 to -0.11)
ages <=65 y · intensive SBP <120 mm Hg vs standard <140 mm Hg · SPRINT participants with hypertension, age 65 y or younger · n = 449 · rct · Pruzin JJ, et al. Hypertension. 2025. PMID 41159258
↓ -34% Intensive SBP control, age 66-75 y · Intensive vs standard systolic BP treatment: WMH volume progression reduced by 34% (change -0.11 asinh-transformed units, 95% CI -0.19 to -0.02)
ages 66-75 y · intensive SBP <120 mm Hg vs standard <140 mm Hg · SPRINT participants with hypertension, age 66-75 y · n = 449 · rct · Pruzin JJ, et al. Hypertension. 2025. PMID 41159258

Cortical thickness Mean cortical thickness (MRI) (mm) · physical parameter

1 3 1

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Cortical thickness, linear decline with age (healthy adults 19-62 y), -4.5 um per year.

Change with age (1)

↓ -4.5 um per year Cortical thickness, linear decline with age (healthy adults 19-62 y) · Linear decline of cortical thickness of 4.5 +/- 1.2 um per year, confirming a previous result
ages 19-62 y · healthy adults aged 19-62 y (7 T MRI) · cross sectional · Carradus AJ, et al. Neurobiol Aging. 2020. PMID 33049517

Link to healthspan (3)

↑ ratio 1.24 (1.13 to 1.37) EOAD-signature cortical atrophy and progression to dementia → dementia (progression from MCI) · HR 1.24 per 1-SD increase in atrophy within the EOAD signature, MCI due to early-onset AD
MCI due to early-onset AD, 40-64 y (LEADS) · n = 130 · prospective cohort · Paranhos T, et al. Neurology. 2026. PMID 42647766
↓ ratio 0.57 Entorhinal cortical thickness and incident cognitive impairment → incident cognitive impairment (CDR >0) · Harvard Aging Brain Study, CDR 0 at baseline, 5-y follow-up; entorhinal thickness HR 0.57-0.65 across models; value is the lower end of the stated range
cognitively unimpaired older adults · n = 231 · prospective cohort · Petersen KK, et al. J Int Neuropsychol Soc. 2025. PMID 40842062
↑ ratio 3.4 AD-signature cortical thinning and AD dementia in cognitively normal adults → Alzheimer disease dementia · AD-signature cortical thickness predicted time to AD dementia; 1 SD of thinning increased dementia risk by 3.4
cognitively normal adults, two samples (15 converters, 50 stable) · n = 65 · prospective cohort · Dickerson BC, et al. Neurology. 2011. PMID 21490323

Remedy and magnitude (1)

↑ 1.18% Resistance training: parahippocampal cortical thickness, high MCI risk · 12-week lower-limb resistance training vs waiting list; Group x Time interaction for right parahippocampal thickness; +1.18% in high-MCI-risk exercisers (uncorrected p = 0.08)
12 wk · lower-limb resistance training · older adults 60-85 y, low and high MCI risk · n = 50 · rct · Kusleikiene S, et al. Brain Res Bull. 2025. PMID 39954817

Retinal nerve-fibre layer RNFL thickness (OCT) (um) · physical parameter

3 2 2

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: RNFL thickness, healthy ageing, Cirrus OCT, -0.44 um per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (3)

↓ -0.44 um per year RNFL thickness, healthy ageing, Cirrus OCT · Pooled longitudinal change in RNFL thickness in healthy populations measured with Cirrus OCT: -0.44 +/- 0.17 um/year
healthy population (51 longitudinal studies) · systematic review · Vilares-Morgado R, et al. Surv Ophthalmol. 2026. PMID 40615051
↓ -0.25 um per year RNFL thickness, healthy ageing, Optovue OCT · Pooled longitudinal change in RNFL thickness in healthy populations measured with Optovue OCT: -0.25 +/- 0.21 um/year
healthy population (51 longitudinal studies) · systematic review · Vilares-Morgado R, et al. Surv Ophthalmol. 2026. PMID 40615051
↓ -0.47 um per year RNFL thickness, healthy ageing, Spectralis OCT · Pooled longitudinal change in RNFL thickness in healthy populations measured with Spectralis OCT: -0.47 +/- 0.27 um/year
healthy population (51 longitudinal studies) · systematic review · Vilares-Morgado R, et al. Surv Ophthalmol. 2026. PMID 40615051

Link to healthspan (2)

↑ ratio 1.15 (1.02 to 1.3) Macular RNFL thinning and 12-year incident dementia (UK Biobank) → dementia · Each 5-um reduction in macular RNFL thickness: HR 1.15; lowest vs highest quintile HR 1.64 (1.17-2.30)
UK Biobank participants with OCT · n = 35,433 · prospective cohort · Wang Y, et al. Alzheimers Dement (N Y). 2025. PMID 40453978
↑ ratio 1.44 (1.19 to 1.75) Thinner RNFL and incident dementia (population-based) → dementia · Rotterdam Study, OCT; HR per SD decrease in RNFL thickness, mean 4.5 y follow-up; Alzheimer disease HR 1.43 (1.15-1.78)
general population of Dutch adults · n = 3,289 · prospective cohort · Mutlu U, et al. JAMA Neurol. 2018. PMID 29946702

Remedy and magnitude (2)

↓ -1.86 um Citicoline eye drops added to IOP-lowering therapy, progressing glaucoma · 3-year RNFL loss 1.86 um with citicoline vs 2.99 um with placebo (P=0.02)
156 wk · citicoline eye drops 3 times daily · mild-moderate open-angle glaucoma progressing despite IOP <=18 mmHg · n = 80 · rct · Rossetti L, et al. J Glaucoma. 2020. PMID 32541370
↑ 7.15 um (1.08 to 13.22) Phenytoin neuroprotection after acute optic neuritis · RNFL thickness in affected eye at 6 months 81.46 um phenytoin vs 74.29 um placebo; adjusted difference 7.15 um, a 30% reduction in RNFL loss
13 wk · oral phenytoin 4-6 mg/kg/day for 3 months · acute demyelinating optic neuritis, 18-60 y · n = 81 · rct · mechanism: voltage-gated sodium channel inhibition · Raftopoulos R, et al. Lancet Neurol. 2016. PMID 26822749

Sensory

Visual acuity Best-corrected acuity (logMAR) (logMAR) · capacity

3 1 6

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Best-corrected acuity change over 10 years, age 43-54 (Beaver Dam), -0.9 letters per decade.

Change with age (3)

↓ -1.25 letters per decade ETDRS letter score decline per decade, healthy adults 20-80 y · Binocular best-corrected ETDRS letter score decreased 1.25 points per decade
ages 20-80 y · healthy adults · n = 50 · cross sectional · Silva MF, et al. Brain Struct Funct. 2021. PMID 34245381
↓ -0.9 letters per decade Best-corrected acuity change over 10 years, age 43-54 (Beaver Dam) · Change in mean number of letters read correctly over 10 years, right eye: -0.9 (SD 5.5) at 43-54 y
ages 43-54 y at baseline · population-based cohort, Beaver Dam Eye Study · n = 3,684 · prospective cohort · Klein R, et al. Ophthalmology. 2001. PMID 11581046
↓ -11 letters per decade Best-corrected acuity change over 10 years, age 75+ (Beaver Dam) · Change in mean letters read correctly over 10 years, right eye: -11.0 (SD 20.0) at >=75 y
ages >=75 y at baseline · population-based cohort, Beaver Dam Eye Study · n = 3,684 · prospective cohort · Klein R, et al. Ophthalmology. 2001. PMID 11581046

Link to healthspan (1)

↓ -0.005 domain z-score per year per 0.1 logMAR (-0.01 to -0.001) Worse acuity and faster memory decline → cognitive decline (memory) · Per 0.1 logMAR worse baseline acuity, additional annual decline in memory domain z-score (language domain: -0.0035, 95% CI -0.007 to -0.001)
ages 60-94 · Baltimore Longitudinal Study of Aging, mean age 71.1, mean follow-up 6.9 y · n = 1,202 · prospective cohort · Varadaraj V, et al. JAMA Netw Open. 2021. PMID 34269806

Remedy and magnitude (6)

↓ -0.1 logMAR (-0.17 to -0.03) Radiotherapy for neovascular AMD · Mean difference in visual acuity change at 12 months vs no radiotherapy (10 studies, 883 eyes); low-certainty evidence
52 wk · 7.5 to 24 Gy (external beam or brachytherapy) · choroidal neovascularisation secondary to AMD, 18 RCTs · n = 2,430 · meta analysis · Evans JR, et al. Cochrane Database Syst Rev. 2020. PMID 32844399
↑ 5.6 ETDRS letters (4.1 to 7.1) Intravitreal aflibercept 8 mg every 12 weeks (neovascular AMD) · LS mean BCVA change from baseline at week 96, PULSAR; 8 mg q16w +5.5 (4.0-7.0), 2 mg q8w +6.6 (5.2-8.0) letters
96 wk · 8 mg intravitreal every 12 weeks after 3 monthly loading doses · treatment-naive adults >=50 y with nAMD · n = 1,009 · rct · Korobelnik JF, et al. Ophthalmology. 2026. PMID 40876598
↑ 10.7 ETDRS letters (9.4 to 12) Intravitreal faricimab every 8 weeks (diabetic macular oedema) · Adjusted mean BCVA change at 1 year (average of weeks 48-56), YOSEMITE trial (97.52% CI); aflibercept q8w comparator 10.9 letters; RHINE 11.8 letters
52 wk · 6.0 mg intravitreal every 8 weeks · adults with vision loss from centre-involving diabetic macular oedema · n = 1,891 · rct · mechanism: bispecific antibody against angiopoietin-2 and VEGF-A · Wykoff CC, et al. Lancet. 2022. PMID 35085503
↑ 7.2 ETDRS letters Intravitreal ranibizumab 0.5 mg (neovascular AMD) · Mean change in visual acuity at 12 months vs sham injection (sham: -10.4 letters; 0.3 mg arm: +6.5 letters); benefit maintained at 24 months
52 wk · 0.5 mg intravitreal monthly · minimally classic or occult CNV secondary to AMD · n = 716 · rct · mechanism: neutralises all active forms of VEGF-A · Rosenfeld PJ, et al. N Engl J Med. 2006. PMID 17021318
↓ ratio 0.73 (0.54 to 0.99) AREDS antioxidants plus zinc (AMD) · Odds of at least moderate visual acuity loss (>=15 letters) vs placebo; 99% CI as reported
328 wk · vitamin C 500 mg, vitamin E 400 IU, beta carotene 15 mg, zinc 80 mg, copper 2 mg daily · AMD trial participants aged 55-80, average follow-up 6.3 y · n = 3,640 · rct · Age-Related Eye Disease Study Research Group. Arch Ophthalmol. 2001. PMID 11594942
0 logMAR (-0.02 to 0.02) Blue-light filtering spectacle lenses · Mean difference in BCVA vs non-blue-light-filtering lenses (1 RCT, 156 participants); moderate-certainty evidence of no effect
adults, 17 RCTs, follow-up under one day to five weeks · n = 156 · systematic review · Singh S, et al. Cochrane Database Syst Rev. 2023. PMID 37593770

Contrast sensitivity Pelli-Robson / log contrast sensitivity (logCS) · capacity

1 3 4

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Normal ageing decline in frequency-doubling contrast sensitivity, 0.6 dB per decade.

Change with age (1)

↓ 0.6 dB per decade Normal ageing decline in frequency-doubling contrast sensitivity · Approximately linear decrease between ages 15 and 60; slightly greater loss after age 70; no eccentricity dependence
ages 15-60 · 407 normal subjects (761 eyes) aged 15-85 · n = 407 · normative study · Adams CW, et al. Optom Vis Sci. 1999. PMID 10472964

Link to healthspan (3)

↑ ratio 1.12 (1.08 to 1.16) Lower contrast sensitivity and incident self-reported visual disability → self-reported visual disability · Odds per 0.1-unit decrease in baseline binocular logCS; functional threshold 1.60 logCS (sensitivity 67%, specificity 70%)
ages 65+ · NHATS community-dwelling Medicare beneficiaries aged 65+, 1-year follow-up · n = 4,475 · prospective cohort · Xu S, et al. JAMA Ophthalmol. 2026. PMID 42207527
↓ -0.01 domain z-score per year per 0.1 log units (-0.014 to -0.006) Worse contrast sensitivity and faster language decline → cognitive decline (language) · Per 0.1 log units worse baseline CS, additional annual decline in language domain z-score; similar for memory (-0.009), attention (-0.010), visuospatial (-0.010)
ages 60-94 · Baltimore Longitudinal Study of Aging, mean age 71.1, mean follow-up 6.9 y · n = 1,202 · prospective cohort · Varadaraj V, et al. JAMA Netw Open. 2021. PMID 34269806
↑ ratio 1.3 (1.1 to 1.7) Impaired contrast sensitivity and incident walking limitation → mobility limitation · Impaired CS (<1.55 log contrast) vs unimpaired; hazard of persistent walking limitation over 5 years (stair-climbing limitation HR 1.4, 95% CI 1.1-1.8)
ages 70-79 · Health ABC participants aged 70-79 without mobility limitation at baseline · n = 1,862 · prospective cohort · Swenor BK, et al. J Am Geriatr Soc. 2015. PMID 25536849

Remedy and magnitude (4)

↑ 0.29 LogCS (0.23 to 0.35) Multi-wavelength photobiomodulation (non-exudative AMD) · Mean difference vs sham at 12 months at Level E (18 cycles/degree); 1 RCT, 46 eyes; low-certainty evidence
52 wk · non-exudative AMD, AREDS categories 2-4 · n = 46 · meta analysis · mechanism: proposed restoration of mitochondrial function and upregulation of cytoprotective factors in retinal tissue · Henein C, et al. Cochrane Database Syst Rev. 2021. PMID 34097768
↑ 0.15 log units (0.05 to 0.25) Radiotherapy for neovascular AMD · Mean difference in average contrast sensitivity at 12 months vs no radiotherapy (2 studies, 267 eyes); low-certainty evidence
52 wk · 7.5 to 24 Gy · choroidal neovascularisation secondary to AMD · n = 267 · meta analysis · Evans JR, et al. Cochrane Database Syst Rev. 2020. PMID 32844399
ratio 1.11 (0.92 to 1.33) High-dose intravenous corticosteroids (acute optic neuritis) · Risk ratio of contrast sensitivity in the normal range at 6 months vs placebo, total dose >3000 mg IV (2 trials, 346 participants)
26 wk · total corticosteroid dose greater than 3000 mg intravenously · acute optic neuritis, 6 RCTs, 750 participants · n = 346 · meta analysis · Gal RL, et al. Cochrane Database Syst Rev. 2015. PMID 26273799
-0.01 log CS (-0.03 to 0.01) Blue-blocking spectacle lenses · Mean difference in log CS vs clear lenses, pseudo-RCT crossover design; no observed difference
adults from the general population; 3 included studies, 136 participants in total · systematic review · Lawrenson JG, et al. Ophthalmic Physiol Opt. 2017. PMID 29044670

Hearing Pure-tone average threshold (dB HL) · capacity

4 4 5

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Pure-tone threshold change, older adults (0.25 kHz), 0.7 dB per year.

Change with age (4)

↑ 0.5 dB per year (0.32 to 0.81) PTA(1,2,3 kHz) change with age, adults 71-96 y · Cross-sectional: pure-tone average of 1, 2 and 3 kHz increased 0.5 dB/yr (0.59 SD per decade)
ages 71-96 y · volunteers from a dementia surveillance cohort with symmetric hearing · n = 241 · cross sectional · Gates GA, et al. Ear Hear. 2008. PMID 18998241
↑ 1.35 dB per year Hearing loss progression, high frequencies (Rotterdam Study) · Mean progression of hearing loss 0.29 dB/year (low frequencies) and 1.35 dB/year (high frequencies) over 4.4 y
ages mean age 71.1 y · ageing adults, population-based Rotterdam Study · n = 675 · prospective cohort · Rigters SC, et al. Audiol Neurootol. 2018. PMID 30537711
↑ 0.7 dB per year Pure-tone threshold change, older adults (0.25 kHz) · Longitudinal (mean 6.4 y): average threshold change 0.7 dB per year at 0.25 kHz rising to 1.2 dB per year at 8 kHz; about 1 dB per year overall for adults 60+
ages 60-81 y at entry · older adults · n = 188 · prospective cohort · Lee FS, et al. Ear Hear. 2005. PMID 15692300
↑ 1.2 dB per year Pure-tone threshold change, older adults (8 kHz) · 1.2 dB per year at 8 kHz (1.23 dB per year at 12 kHz)
ages 60-81 y at entry · older adults · n = 188 · prospective cohort · Lee FS, et al. Ear Hear. 2005. PMID 15692300

Link to healthspan (4)

↑ ratio 1.35 (1.26 to 1.45) Adult-onset hearing loss and incident dementia → dementia · Hearing loss (yes/no) vs none; MCI HR 1.29 (1.11-1.50), Alzheimer's dementia HR 1.56 (1.30-1.87), vascular dementia not significant
50 cohort studies · n = 1,548,754 · meta analysis · Yu RC, et al. Ageing Res Rev. 2024. PMID 38788800
↑ ratio 1.16 (1.07 to 1.27) Hearing worsening and incident dementia (dose-response) → dementia · Per 10-decibel worsening of hearing; 16% increase in dementia risk
50 cohort studies of adults without dementia at baseline, minimum 2 y follow-up · n = 1,548,754 · meta analysis · Yu RC, et al. Ageing Res Rev. 2024. PMID 38788800
↑ ratio 1.28 (1.02 to 1.59) Age-related hearing loss and dementia (prospective cohorts) → dementia · Pure-tone-audiometry-defined hearing loss; prospective cohort studies; cognitive impairment OR 1.22 (1.09-1.36); Alzheimer disease OR 1.69 (0.72-4.00) not significant
36 unique studies, 12 countries · n = 20,264 · meta analysis · Loughrey DG, et al. JAMA Otolaryngol Head Neck Surg. 2018. PMID 29222544
↑ ratio 1.24 (1.05 to 1.48) Hearing loss (PTA >25 dB) and incident cognitive impairment → cognitive impairment · Better-ear pure-tone average 0.5-4 kHz >25 dB vs normal hearing; annual 3MS decline -0.65 vs -0.46 points/year; risk linear with severity of baseline loss
Health ABC participants, mean age 77.4, without prevalent cognitive impairment, 6 y follow-up · n = 1,984 · prospective cohort · Lin FR, et al. JAMA Intern Med. 2013. PMID 23337978

Remedy and magnitude (5)

↓ ratio 2.61 (1.86 to 3.68) Hyperbaric oxygen plus medical therapy (sudden sensorineural hearing loss) · Odds of hearing recovery vs medical therapy alone, 10 studies in meta-analysis; HBOT + systemic steroids vs steroids OR 2.54 (1.63-3.97)
20 studies (16 RCTs, 4 prospective); 1087 HBOT, 600 medical therapy alone · n = 1,687 · meta analysis · Alter IL, et al. Laryngoscope. 2026. PMID 40747804
↓ ratio 0.81 (0.76 to 0.87) Hearing aids / cochlear implants and long-term cognitive decline → cognitive decline · Hazard of any cognitive decline in hearing-aid users vs uncorrected hearing loss (8 studies, 126 903 participants, 2-25 y follow-up); short-term cognitive test scores ratio of means 1.03 (1.02-1.04)
31 studies (25 observational, 6 trials) of patients with hearing loss · n = 137,484 · meta analysis · Yeo BSY, et al. JAMA Neurol. 2023. PMID 36469314
↓ 10.3 dB (6.5 to 14.1) Hyperbaric oxygen added to medical therapy (sudden sensorineural hearing loss) · Mean difference in absolute hearing gain on pure-tone audiometry vs medical therapy alone (3 RCTs; 88 HBOT vs 62 control); odds of recovery (>=10 dB gain) 4.3 (1.6-11.7)
adults with sudden sensorineural hearing loss (AAO-HNS criteria) · n = 150 · meta analysis · Joshua TG, et al. JAMA Otolaryngol Head Neck Surg. 2022. PMID 34709348
↓ ratio 0.74 (0.63 to 0.87) Adjuvant corticosteroids (acute bacterial meningitis) · Risk of any hearing loss vs placebo; severe hearing loss RR 0.67 (0.51-0.88); benefit confined to high-income countries
25 RCTs, all ages (2511 children, 1517 adults) · n = 4,121 · meta analysis · mechanism: reduces subarachnoid inflammatory response · Brouwer MC, et al. Cochrane Database Syst Rev. 2015. PMID 26362566
0.002 SD units of global cognition (-0.077 to 0.081) Hearing aids plus audiological counselling vs health education (ACHIEVE) → cognitive decline · Difference in 3-year change in global cognition factor score vs health-education control (-0.200 vs -0.202 SD units); prespecified ARIC subgroup showed benefit (p interaction 0.010)
156 wk · audiological counselling and provision of hearing aids, follow-up every 6 months · adults aged 70-84 with untreated hearing loss, no substantial cognitive impairment, 4 US sites · n = 977 · rct · Lin FR, et al. Lancet. 2023. PMID 37478886

Olfaction Odor identification score (UPSIT / Sniffin' Sticks) (score) · capacity

2 4 4

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

SMD 0.06 (-0.17 to 0.29) Odor identification, 30-39 vs 40-49 years · Cohen's d between 30-39.9 and 40-49.9-year-olds = 0.06 (no decline before the fifth decade)
ages 30-39 y vs 40-49 y · healthy humans · meta analysis · Zhang C, et al. Ageing Res Rev. 2017. PMID 28830800
↓ SMD 1.12 (1.06 to 1.45) Odor identification, age 35-55 vs >55 years · Meta-analysis of healthy humans: Cohen's d for 35-55-year-olds vs >55-year-olds = 1.12 (very large effect)
ages 35-55 y vs >55 y · healthy humans · meta analysis · Zhang C, et al. Ageing Res Rev. 2017. PMID 28830800

Link to healthspan (4)

↓ SMD -0.16 (-0.46 to 0.14) Odour identification in subjective cognitive decline → subjective cognitive decline · Standardised difference in olfactory identification, SCD vs healthy controls aged 50+ (Hedges g, 5 studies); small, not significant
ages 50+ · 5 studies of SCD vs age-matched healthy controls · meta analysis · Jobin B, et al. J Alzheimers Dis. 2021. PMID 33459721
↑ ratio 2.02 (1.27 to 3.29) Poor olfaction and incident coronary heart disease → coronary heart disease · Poor (score 0-8) vs good (11-12) on 12-item odour identification test; adjusted marginal risk ratio at year 4 (year 2: 2.06, 1.04-4.53; year 6: 1.59, 1.13-2.35; year 8: 1.22, 0.88-1.70, attenuating)
ARIC participants without CHD at visit 5, mean age 75.4, 9.6 y follow-up · n = 5,142 · prospective cohort · Chamberlin KW, et al. JAMA Otolaryngol Head Neck Surg. 2026. PMID 41165715
↑ ratio 1.06 (1.03 to 1.08) Odour identification errors and all-cause mortality → mortality · Per additional incorrect answer on the 16-item Sniffin' Sticks identification test, 6-year mortality (12-year HR 1.05, 95% CI 1.03-1.08); dementia mediated 23%, frailty 11%, malnutrition 5% of the 6-year association
ages 60-99 · SNAC-K population-based cohort, Stockholm, mean age 71.9 · n = 2,524 · prospective cohort · Ruane R, et al. JAMA Otolaryngol Head Neck Surg. 2025. PMID 40208577
↑ ratio 2.02 (1.17 to 3.48) Anosmia and inability to complete a 400-m walk → mobility limitation · Anosmia (BSIT 0-6) vs good olfaction (11-12), odds of being unable to do the 400-m test at year 8 (year 10: 2.73, 1.40-5.35); 20-m usual walk declined 0.01 m/s/year faster (0.007-0.013)
Health ABC participants, mean age 75.6, followed up to 7 y · n = 2,500 · prospective cohort · Yuan Y, et al. JAMA Otolaryngol Head Neck Surg. 2024. PMID 38236595

Remedy and magnitude (4)

↑ 8 UPSIT points (6.3 to 9.7) Dupilumab vs omalizumab (CRSwNP with asthma, EVEREST) · LS mean difference in UPSIT change from baseline, dupilumab over omalizumab, at week 24 (active comparator); nasal polyp score difference -1.60 (-1.96 to -1.25)
24 wk · dupilumab 300 mg SC every 2 weeks vs omalizumab weight/IgE-tiered every 2 or 4 weeks, with mometasone nasal spray · adults with severe uncontrolled CRSwNP and physician-diagnosed asthma, 17 countries · n = 360 · rct · De Corso E, et al. Lancet Respir Med. 2025. PMID 41033334
↓ -0.37 loss-of-smell VAS points Mepolizumab (severe CRSwNP, SYNAPSE) · Treatment difference vs placebo in loss-of-smell VAS score from baseline to week 52; larger with fewer prior surgeries (1 surgery: -1.29)
52 wk · 100 mg subcutaneously every 4 weeks plus standard of care · adults with severe bilateral CRSwNP and impaired smell at baseline (206 mepolizumab, 201 placebo) · n = 407 · rct · Mullol J, et al. Rhinology. 2024. PMID 38217844
↑ 3.67 TDI points (0.05 to 7.29) Intranasal platelet-rich plasma (post-COVID-19 smell loss) · Greater improvement in Sniffin' Sticks TDI vs saline at 3 months; responder rate 57.1% vs 8.3% (OR 12.5); gain in discrimination but not identification or threshold
13 wk · three intranasal injections into the olfactory clefts · COVID-19 smell loss 6-12 months, UPSIT <=33; 35 recruited, 26 completed · n = 26 · rct · Yan CH, et al. Int Forum Allergy Rhinol. 2023. PMID 36507615
↑ 10.57 UPSIT points (9.4 to 11.74) Dupilumab (severe chronic rhinosinusitis with nasal polyps) · LS mean difference vs placebo in UPSIT (0-40) at week 24, pooled SINUS-24/SINUS-52; mean improvement 10.54 from baseline 13.90; loss-of-smell score difference -1.04 (-1.17 to -0.91)
24 wk · 300 mg subcutaneously every 2 weeks · adults with severe CRSwNP, mean disease duration 11 y, 63% prior surgery · n = 724 · rct · mechanism: type 2 inflammation blockade (IL-4/IL-13 signalling) · Mullol J, et al. J Allergy Clin Immunol Pract. 2022. PMID 34628065

Proprioception Joint position sense error (degrees) · capacity

1 1 2

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↑ 3 degrees (2.64 to 3.36) Cervical joint position error, >65 vs <65 years · Cervical JPE in flexion 4.28 +/- 1.29 deg (>65 y) vs 1.48 +/- 1.37 deg (<65 y); stated mean difference 3.00 deg
ages >65 y vs <65 y · adults >65 y (n=100) vs <65 y (n=100) · n = 200 · cross sectional · Reddy RS, et al. Healthcare (Basel). 2023. PMID 37444758

Link to healthspan (1)

↑ ratio 1.23 (0.94 to 1.61) Cervical joint position error and falls over 1 year → falls (>=1 in 12 months) · Multivariable logistic model (age, sex, walking aid, fall history, iconFES, cervical ROM): mean cervical JPE OR 1.23 per degree; univariate OR 1.22 (0.98-1.53)
community-dwelling healthy older adults · n = 95 · prospective cohort · Roman de Mettelinge T, et al. Eur Geriatr Med. 2023. PMID 37119446

Remedy and magnitude (2)

↓ ratio 0.55 (0.347 to 0.869) Proprioception training for sports-injury prevention → sports injury · Risk ratio of sports injury with proprioception training vs control (strength training RR 0.315, 0.207-0.480; stretching RR 0.963, no effect)
25 RCTs, 26 610 participants, 3464 injuries · n = 26,610 · meta analysis · Lauersen JB, et al. Br J Sports Med. 2014. PMID 24100287
↓ SMD 0.52 Resistance-band strength training (chronic ankle instability) · Improvement in ankle joint position sense at 140 degrees; post hoc Cohen's d, strength vs balance training (vibration sense d = 0.25)
6 wk · 35 min per day, two times per week · adults aged 18-30 with chronic ankle instability (CAIT <=24) · n = 29 · rct · Yekdaneh A, et al. J Am Podiatr Med Assoc. 2024. PMID 39058626

Vibration / touch Vibration perception threshold (V; um) · capacity

3 3 2

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Vibration perception threshold rise, healthy adults (multi-frequency vibrometry), 0.09 dB per year (0.09 to 0.59).

Change with age (3)

↑ 0.09 dB per year (0.09 to 0.59) Vibration perception threshold rise, healthy adults (multi-frequency vibrometry) · VPTs at finger pulps and metatarsal heads deteriorated 0.09-0.59 dB per year depending on site/frequency
ages adults >18 y (mean 46 y) · healthy randomly selected adults, southern Sweden · n = 924 · normative study · Ekman L, et al. PLoS One. 2021. PMID 33822804
↑ 0.3 dB per year Vibrotactile threshold rise, finger, 125 Hz · Effect of age 0.3 dB per year at 125 Hz vs 0.2 dB per year at 31.5 Hz (middle and little finger)
ages working age · non-vibration-exposed working populations · n = 378 · normative study · Wild P, et al. Ergonomics. 2001. PMID 11373025
↑ 0.2 dB per year Vibrotactile threshold rise, finger, 31.5 Hz · Effect of age 0.2 dB per year at 31.5 Hz
ages working age · non-vibration-exposed working populations · n = 378 · normative study · Wild P, et al. Ergonomics. 2001. PMID 11373025

Link to healthspan (3)

↑ ratio 4.36 (2.07 to 9.16) Diabetic neuropathy (VPT >25 V) and incident dementia (type 2 diabetes) → dementia · Incidence rate ratio with vs without DPN defined by VPT >25 V; cerebrovascular disease IRR 1.45 (1.18-1.80); results similar with age-sex-height-adjusted threshold
Steno Diabetes Center Copenhagen register cohort, type 2 diabetes, mean age 59.9, 1998-2020 · n = 9,395 · prospective cohort · Wiggers A, et al. Diabetes Obes Metab. 2026. PMID 42108425
↑ ratio 2.587 (1.277 to 5.242) High vibration perception threshold and diabetic foot ulceration → diabetic foot ulceration · VPT >=25 volts vs lower, multivariate Cox hazard ratio for first diabetic foot ulcer over 6 years (adjusted for age, sex, diabetes duration); specificity 0.89, sensitivity 0.39
people with diabetes without prior ulcer or critical limb ischaemia, multicentre, 2012-2017 · n = 308 · prospective cohort · Panagoulias GS, et al. Front Endocrinol (Lausanne). 2020. PMID 33013702
↑ 16 seconds (400-m walk time) Poor vibration perception threshold and slower 400-m walk → endurance walking performance · VPT >130 um vs better, fully adjusted linear mixed model: slower 400-m Long Distance Corridor Walk completion time, plus 4.2 additional seconds per year of slowing over 6 years
Health ABC community-dwelling older adults, mean age 76.5 · n = 2,393 · prospective cohort · Lange-Maia BS, et al. Arch Phys Med Rehabil. 2016. PMID 26343170

Remedy and magnitude (2)

↓ SMD -1 Home-based walking and resistance exercise during neurotoxic chemotherapy · Effect size on CIPN signs (tactile sensitivity by monofilaments) at mid-intervention vs nutrition-education control; post-intervention ES -0.1; CIPN-20 symptoms ES -0.9 mid, -0.5 post
12 wk · home-based, individually tailored, moderate intensity, progressive walking and resistance training · patients aged 65 +/- 11 starting neurotoxic chemotherapy (breast, GI, myeloma) · n = 19 · rct · Kleckner IR, et al. Support Care Cancer. 2024. PMID 39304604
↓ SMD 0.25 Resistance-band strength training (chronic ankle instability) · Improvement in vibration sense (fifth finger), post hoc Cohen's d, strength vs balance training; ankle proprioception d = 0.52
6 wk · 35 min per day, two times per week · adults aged 18-30 with chronic ankle instability · n = 29 · rct · Yekdaneh A, et al. J Am Podiatr Med Assoc. 2024. PMID 39058626

Cognitive

Processing speed Digit-symbol substitution / simple reaction time (items/90 s; ms) · capacity

2 3 5

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Annual DSST decline, normal hearing, -0.63 DSST points per year (-0.75 to -0.51) · the age range was not stated, so ages 30–80 are assumed.

Change with age (2)

↓ -0.83 DSST points per year (-0.94 to -0.73) Annual DSST decline, hearing loss · Digit Symbol Substitution Test annual score change in older adults with baseline hearing loss (pure-tone average >25 dB); 32% greater than normal hearing
ages mean age 77.4 y · older adults with hearing loss (Health ABC) · n = 1,162 · prospective cohort · Lin FR, et al. JAMA Intern Med. 2013. PMID 23337978
↓ -0.63 DSST points per year (-0.75 to -0.51) Annual DSST decline, normal hearing · Digit Symbol Substitution Test annual score change in older adults with normal hearing (pure-tone average <=25 dB), Health ABC, 6-year follow-up
ages mean age 77.4 y · community-dwelling older adults without cognitive impairment (Health ABC) · n = 1,984 · prospective cohort · Lin FR, et al. JAMA Intern Med. 2013. PMID 23337978

Link to healthspan (3)

↑ ratio 2.55 (1.51 to 4.29) Lowest DSST quartile and 8-year mortality (Japanese elders) → all-cause mortality · First (lowest) vs fourth DSST quartile; multivariate Cox HR
ages 70+ · community-dwelling Japanese adults aged 70+ · n = 811 · prospective cohort · Iwasa H, et al. J Epidemiol. 2014;24(1):52-9. PMID 24240629
↑ ratio 1.87 DSST < 25 and 13-year mortality (Health ABC) → all-cause mortality · DSST < 25 (21.9% of cohort) vs higher scores; top predictor among 825 measures
ages 70-79 · well-functioning older adults (Health, Aging and Body Composition Study) · n = 3,067 · prospective cohort · Swindell WR, et al. Rejuvenation Res. 2012;15(4):405-13. PMID 22607624
↓ ratio 0.86 (0.8 to 0.93) Higher DSST score and all-cause mortality in middle age (ARIC) → all-cause mortality · HR per 7-point higher Digit Symbol Substitution Test score, fully adjusted
ages 48-67 · middle-aged community adults (Atherosclerosis Risk in Communities) · prospective cohort · Pavlik VN, et al. Am J Epidemiol. 2003;157(4):327-34. PMID 12578803

Remedy and magnitude (5)

↓ -10.6 ms (-12.1 to -9.2) Bacopa monnieri extract, choice reaction time · Meta-analysis of placebo-controlled trials of standardised Bacopa monnieri extract, >=12 weeks dosing: decreased choice reaction time
12 wk · chronic >=12 weeks, standardised extract, no co-medication · 9 RCTs, 437 subjects analysed (518 enrolled) · n = 437 · meta analysis · Kongkeaw C, et al. J Ethnopharmacol. 2014. PMID 24252493
↓ -2.78 SDMT points (-5.23 to -0.33) Aerobic exercise plus sham cognitive rehabilitation (SDMT), CogEx · Least-squares mean difference in SDMT at 12 weeks vs double-sham group (n=67), exercise plus sham cognitive rehabilitation arm (n=71), progressive MS
12 wk · 2 sessions/week for 12 weeks, individualised aerobic training on a recumbent arm-leg stepper · progressive multiple sclerosis, aged 25-65, impaired SDMT · n = 311 · rct · Feinstein A, et al. Lancet Neurol. 2023. PMID 37739574
-1.3 SDMT points (-3.75 to 1.16) Cognitive rehabilitation plus aerobic exercise (SDMT), CogEx · Least-squares mean difference in SDMT at 12 weeks vs double-sham group, combined cognitive rehabilitation plus exercise arm (n=70), progressive MS
12 wk · 2 sessions/week for 12 weeks; computer-based incremental processing-speed training plus aerobic stepper training · progressive multiple sclerosis, aged 25-65, impaired SDMT · n = 311 · rct · Feinstein A, et al. Lancet Neurol. 2023. PMID 37739574
0.8 SDMT points (0.9 to 2.5) Treadmill training alone (SDMT) · Within-group improvement in SDMT after treadmill training without VR (active control, per-protocol n=51), p=0.358
6 wk · 3 sessions/week for 6 weeks · people with multiple sclerosis · n = 124 · rct · Galperin I, et al. J Neurol. 2023. PMID 36357586
↑ 4.4 SDMT points (1.9 to 6.8) Treadmill training with virtual reality (SDMT) · Within-group improvement in Symbol Digit Modalities Test after treadmill training plus VR in people with multiple sclerosis (per-protocol n=53); group x time p=0.027 vs treadmill alone
6 wk · 3 sessions/week for 6 weeks · people with multiple sclerosis · n = 124 · rct · Galperin I, et al. J Neurol. 2023. PMID 36357586

Working memory Digit span / n-back (span; d') · capacity

2 1 6

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: No longitudinal decline in digit span backwards in midlife women (SWAN), 0 DSB score (correct trials) per year (-0.02 to 0.02) · the age range was not stated, so ages 30–80 are assumed.

Change with age (2)

↓ -0.05 SD per year Working-memory construct lower with age (PROTECT Norge, cross-sectional) · Online battery; latent working-memory construct; age coefficient adjusted for demographics
ages 50+ · Norwegian adults aged 50+ (PROTECT Norge) · n = 3,215 · cross sectional · Ushakova A, et al. Sci Rep. 2025;15(1):42357. PMID 41309850
0 DSB score (correct trials) per year (-0.02 to 0.02) No longitudinal decline in digit span backwards in midlife women (SWAN) · Within-woman annualized slope, digit span backwards (0-12 correct trials), chronological aging model
ages mean 54 at baseline · midlife women (Study of Women's Health Across the Nation) · n = 2,124 · prospective cohort · Karlamangla AS, et al. PLoS One. 2017;12(1):e0169008. PMID 28045986

Link to healthspan (1)

ratio 0.98 (0.89 to 1.08) Attention/working-memory factor and all-cause mortality (HANDLS) → all-cause mortality · HR per unit of PCA2 (attention/working memory incl. digit span forward/backward), Model 1
ages 30-64 · urban middle-aged White and African American adults (HANDLS) · n = 2,260 · prospective cohort · Weiss J, et al. Sci Rep. 2021;11(1):19849. PMID 34615909

Remedy and magnitude (6)

↑ SMD 0.392 Aerobic exercise, working memory (healthy middle-aged and older adults) · Pooled effect of aerobic exercise RCTs on working memory in healthy adults aged 45+
largest effects after 13-24 weeks of progression-intensity general aerobic exercise, 20-45 min/session, 5-7 days/week · healthy middle-aged and older adults aged 45+, 42 RCTs · n = 2,881 · meta analysis · Ye M, et al. Int J Nurs Stud. 2024. PMID 39326271
↑ SMD 0.714 (0.072 to 1.355) Dual-task training, working memory (MCI or dementia) · Meta-analysis of simultaneous dual-task training RCTs in older adults with cognitive impairment
older adults with MCI or dementia, 20 RCTs · n = 1,477 · meta analysis · Ye JY, et al. Int J Nurs Stud. 2024. PMID 38703695
↑ SMD 0.72 (0.23 to 1.2) Non-invasive brain stimulation plus cognitive training, attention/working memory (AD, follow-up) · Attention/working memory at evaluation follow-up in Alzheimer's disease after NIBS combined with cognitive training
Alzheimer's disease and MCI, 15 studies · n = 685 · meta analysis · Yang T, et al. Alzheimers Res Ther. 2024. PMID 38937842
↑ SMD 1.21 (-0.22 to 2.65) Closed-skill (aerobic-dominated) exercise, working memory (children with ADHD) · Network meta-analysis: closed-skill activities had the highest probability of being most effective for working memory (SUCRA 75.9%)
children and adolescents with ADHD, 44 studies in meta-analysis · n = 1,757 · meta analysis · Zhu F, et al. Front Public Health. 2023. PMID 37033046
↑ SMD 0.54 (0.2 to 0.88) Cognitive training, memory span (multiple sclerosis) · Cochrane meta-analysis of neuropsychological rehabilitation in MS: cognitive training, memory span
people with MS, mean age 44.6 y, 20 studies · n = 986 · meta analysis · Rosti-Otajarvi EM, et al. Cochrane Database Syst Rev. 2014. PMID 24515630
↑ SMD 0.33 (0.09 to 0.57) Cognitive training, working memory (multiple sclerosis) · Cochrane meta-analysis of neuropsychological rehabilitation in MS: cognitive training vs other/no intervention, working memory
people with MS, mean age 44.6 y, 20 studies · n = 986 · meta analysis · Rosti-Otajarvi EM, et al. Cochrane Database Syst Rev. 2014. PMID 24515630

Episodic memory Word-list delayed recall (words) · capacity

3 4 8

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (3)

↓ -0.036 words per year, per additional year of baseline age per year Delayed free verbal recall: additional yearly decline per year of baseline age · Cognitively normal older adults (HELIAD), Greek Verbal Learning Test, ~3-year follow-up: additional yearly decrease in delayed free verbal recall for each additional year of age at baseline
ages mean 73.82 y · cognitively normal older adults, 761 with follow-up (1607 at baseline) · n = 761 · prospective cohort · Liampas I, et al. Clin Neuropsychol. 2023. PMID 35400289
↑ 0.028 AVLT points per year (difference in slope) per year (0.023 to 0.032) Favourable vs unfavourable lifestyle: slower AVLT memory decline · 10-year population cohort of Chinese adults 60+: participants with 4-6 healthy lifestyle factors had slower memory decline than those with 0-1 factors, by this many points per year
ages 60+ (mean 72.23 y) · Chinese adults aged 60+ with normal cognition · n = 29,072 · prospective cohort · Jia J, et al. BMJ. 2023. PMID 36696990
↓ -0.047 SD per year (difference in slope) per year (-0.068 to -0.025) >=2 deprivation-related adverse childhood experiences: faster episodic memory decline · CHARLS, adults 45-97 without baseline cognitive impairment, 2011-2015: annual decline in episodic memory z-score vs no deprivation exposure
ages 45-97 (mean 57.2 y) · middle-aged and older Chinese adults (CHARLS) · n = 6,466 · prospective cohort · Lin L, et al. JAMA Netw Open. 2022. PMID 36367722

Link to healthspan (4)

↑ ratio 2.14 (1.59 to 2.87) Imperfect MMSE delayed recall and incident dementia (preDIVA) → dementia · Imperfect score on MMSE delayed-recall item vs perfect; Cox HR
community-dwelling older adults in primary care (preDIVA trial cohort) · n = 3,454 · prospective cohort · van Wanrooij LL, et al. Ann Fam Med. 2019;17(5):412-418. PMID 31501202
↑ ratio 1.47 (1.29 to 1.68) Poorer memory performance and 10-year all-cause mortality (PROSPER) → all-cause mortality · Lower memory-test performance; multivariable Cox HR
ages mean 78 · dementia-free older adults (PROSPER MRI substudy) · n = 547 · prospective cohort · Rostamian S, et al. Am J Med. 2019;132(12):1466-1474.e4. PMID 31228412
↑ ratio 1.52 (1.27 to 1.8) Zero of three words recalled and 10-year mortality (NEDICES) → all-cause mortality · MMSE three-word delayed recall score 0 vs 3; adjusted for sex, age, education, comorbidity
ages 65+ · non-demented community elders, central Spain (NEDICES) · n = 3,778 · prospective cohort · Villarejo A, et al. Int J Geriatr Psychiatry. 2011;26(2):182-7. PMID 20652904
↓ ratio 0.9 (0.84 to 0.97) Delayed Word Recall score and all-cause mortality in middle age (ARIC) → all-cause mortality · HR per 1-point higher Delayed Word Recall Test score, fully adjusted
ages 48-67 · middle-aged community adults (Atherosclerosis Risk in Communities) · prospective cohort · Pavlik VN, et al. Am J Epidemiol. 2003;157(4):327-34. PMID 12578803

Remedy and magnitude (8)

↑ SMD 0.06 (0.03 to 0.1) Daily multivitamin-mineral, episodic memory (COSMOS meta-analysis) · Meta-analysis of three non-overlapping COSMOS cognitive substudies (Clinic n=573, Mind n=2158, Web n=2472), MVM vs placebo
daily multivitamin-mineral supplement · US adults aged 60+ (COSMOS substudies) · meta analysis · Vyas CM, et al. Am J Clin Nutr. 2024. PMID 38244989
↑ SMD 0.32 (0.01 to 0.63) Resistance exercise, memory function (MCI or dementia) · Network meta-analysis of exercise RCTs in MCI/dementia: resistance exercise vs control on memory cognition
patients with MCI or dementia, 71 trials · n = 5,606 · meta analysis · Huang X, et al. J Sport Health Sci. 2022. PMID 34004389
↑ SMD 0.37 (0.04 to 0.69) Cognitive training, verbal memory (Parkinson's disease MCI/dementia) · Cochrane review, cognitive training vs control at end of 4-8 week treatment, verbal memory
4-8 weeks of cognitive training · PD with dementia or MCI, 5 trials · n = 160 · meta analysis · Orgeta V, et al. Cochrane Database Syst Rev. 2020. PMID 32101639
↑ SMD 0.22 (0.02 to 0.42) Cognitive training plus other neuropsychological rehabilitation, delayed memory (MS) · Cochrane meta-analysis in multiple sclerosis: combined cognitive training and other neuropsychological rehabilitation, delayed memory
people with MS, mean age 44.6 y, 20 studies · n = 986 · meta analysis · Rosti-Otajarvi EM, et al. Cochrane Database Syst Rev. 2014. PMID 24515630
↑ SMD 0.12 (0.002 to 0.23) Daily multivitamin-mineral, episodic memory (COSMOS-Clinic) · In-person neuropsychological testing, 2-year change in episodic memory, MVM vs placebo
104 wk · daily multivitamin-mineral supplement for 2 years · US adults aged 60+ (COSMOS-Clinic subcohort) · n = 573 · rct · Vyas CM, et al. Am J Clin Nutr. 2024. PMID 38244989
↑ 3.1 years of age-related memory change (equivalent) Daily multivitamin, immediate recall (COSMOS-Web) · ModRey immediate recall at 1 year, multivitamin (Centrum Silver) vs placebo, expressed by the authors as years of age-related memory change
52 wk · daily multivitamin/multimineral · older adults (COSMOS-Web) · n = 3,562 · rct · Yeung LK, et al. Am J Clin Nutr. 2023. PMID 37244291
SMD 0.07 (-0.04 to 0.17) Exercise (aerobic, strength, functional), episodic memory composite (MEDEX) · Exercise vs no exercise, episodic memory composite difference at 6 months (0.49 vs 0.42), older adults with subjective cognitive concerns; 2x2 factorial with MBSR
26 wk · target >=300 min/week, group classes plus home practice; interventions lasted 18 months (primary endpoint 6 months) · older adults aged 65-84 with subjective cognitive concerns · n = 585 · rct · Lenze EJ, et al. JAMA. 2022. PMID 36511926
↑ 0.09 z-score (-0.05 to 0.23) Mediterranean diet plus nuts, memory composite (PREDIMED) · Adjusted mean z-score change from baseline of the memory composite (RAVLT, Verbal Paired Associates), Mediterranean diet plus mixed nuts; control diet -0.17 (-0.32 to -0.01); P = .04 vs controls
mixed nuts 30 g/day; median follow-up 4.1 years · cognitively healthy older adults at high cardiovascular risk, mean age 66.9 y (334 retested) · n = 447 · rct · Valls-Pedret C, et al. JAMA Intern Med. 2015. PMID 25961184

Executive function Trail Making B / Stroop (s) · capacity

1 3 9

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↓ -0.019 SD per year (difference in slope) per year (-0.034 to -0.004) >=2 deprivation-related adverse childhood experiences: faster executive function decline · CHARLS 2011-2015: annual decline in executive function z-score vs no deprivation exposure
ages 45-97 (mean 57.2 y) · middle-aged and older Chinese adults (CHARLS) · n = 6,466 · prospective cohort · Lin L, et al. JAMA Netw Open. 2022. PMID 36367722

Link to healthspan (3)

↑ ratio 1.21 (1.07 to 1.37) Combined Trails A/B time and frailty (Framingham) → frailty · Odds of Liver Frailty Index >= 4.5 per unit of combined Trails A/B (unit not stated in abstract)
ages median 70 · Framingham Heart Study participants without cirrhosis · n = 1,208 · cross sectional · Mehta M, et al. Am J Med. 2021;134(12):1530-1538. PMID 34464599
↑ ratio 1.49 (1.31 to 1.7) Poorer executive function and 10-year all-cause mortality (PROSPER) → all-cause mortality · Lower executive-function performance; multivariable Cox HR
ages mean 78 · dementia-free older adults (PROSPER MRI substudy) · n = 547 · prospective cohort · Rostamian S, et al. Am J Med. 2019;132(12):1466-1474.e4. PMID 31228412
↑ ratio 3.3 (1.4 to 7.6) Impaired Trail Making B and onset of physical frailty (WHAS II) → frailty · Binary TMT-B impairment indicator; Cox HR adjusted for depressive symptoms, age, education, race and other tests
community-dwelling older women (Women's Health and Aging Study II) · n = 331 · prospective cohort · Gross AL, et al. J Gerontol A Biol Sci Med Sci. 2016;71(12):1624-1630. PMID 27084314

Remedy and magnitude (9)

↑ SMD 0.24 Exercise (any), executive function (umbrella meta-meta-analysis) · Pooled effect of exercise on executive function across 133 systematic reviews of RCTs, all ages and populations
all populations and ages, 2724 RCTs · n = 258,279 · meta analysis · Singh B, et al. Br J Sports Med. 2025. PMID 40049759
↑ SMD 0.343 Aerobic exercise, cognitive flexibility (healthy middle-aged and older adults) · Pooled effect of aerobic exercise RCTs on cognitive flexibility in healthy adults aged 45+
largest effects after 13-24 weeks of progression-intensity mind-body exercise, 46-60 min/session, 5-7 days/week · healthy middle-aged and older adults aged 45+, 42 RCTs · n = 2,881 · meta analysis · Ye M, et al. Int J Nurs Stud. 2024. PMID 39326271
↑ SMD 0.229 Aerobic exercise, inhibitory control (healthy middle-aged and older adults) · Pooled effect of aerobic exercise RCTs on inhibitory control in healthy adults aged 45+
greatest effects after 13-24 weeks of low-intensity general aerobic exercise, 20-45 min/session, 3-4 days/week · healthy middle-aged and older adults aged 45+, 42 RCTs · n = 2,881 · meta analysis · Ye M, et al. Int J Nurs Stud. 2024. PMID 39326271
↑ SMD 0.85 (0.21 to 1.49) Resistance exercise, executive function (MCI or dementia) · Network meta-analysis of exercise RCTs in MCI/dementia: resistance exercise had the highest probability of being most effective for executive function
patients with MCI or dementia, 71 trials · n = 5,606 · meta analysis · Huang X, et al. J Sport Health Sci. 2022. PMID 34004389
↓ -17.9 ms (-24.6 to -11.2) Bacopa monnieri extract, Trail B · Meta-analysis of placebo-controlled trials of standardised Bacopa monnieri extract, >=12 weeks dosing: shortened Trail B test time
12 wk · chronic >=12 weeks, standardised extract, no co-medication · 9 RCTs, 437 subjects analysed (518 enrolled) · n = 437 · meta analysis · Kongkeaw C, et al. J Ethnopharmacol. 2014. PMID 24252493
↑ SMD 0.61 Acute alpha-GPC 630 mg, Stroop total score (young men) · Crossover RCT: change in Stroop total score 60 min after 630 mg A-GPC vs placebo (13.0 +/- 8.2 vs 5.2 +/- 9.0, p = 0.013), resistance-trained men
single 630 mg dose of alpha-glycerylphosphorylcholine, tested 60 min after ingestion · resistance-trained males, mean age 31.3 y · n = 20 · rct · Kerksick CM, et al. Nutrients. 2024. PMID 39683633
SMD 0.07 (-0.03 to 0.18) Exercise (aerobic, strength, functional), executive function composite (MEDEX) · Exercise vs no exercise, executive function composite difference at 6 months (0.39 vs 0.32), older adults with subjective cognitive concerns
26 wk · target >=300 min/week; interventions lasted 18 months (primary endpoint 6 months) · older adults aged 65-84 with subjective cognitive concerns · n = 585 · rct · Lenze EJ, et al. JAMA. 2022. PMID 36511926
↑ 12.6% Once-weekly resistance training, Stroop performance (senior women) · 12-month RCT, women 65-75: Stroop task performance improved 12.6% in the once-weekly resistance training group; balance-and-tone control deteriorated 0.5%
52 wk · resistance training once weekly for 12 months · community-dwelling women aged 65-75, Vancouver · n = 155 · rct · Liu-Ambrose T, et al. Arch Intern Med. 2010. PMID 20101012
↑ 10.9% Twice-weekly resistance training, Stroop performance (senior women) · 12-month RCT, women 65-75: Stroop task performance improved 10.9% in the twice-weekly resistance training group; control deteriorated 0.5%
52 wk · resistance training twice weekly for 12 months · community-dwelling women aged 65-75, Vancouver · n = 155 · rct · Liu-Ambrose T, et al. Arch Intern Med. 2010. PMID 20101012

Learning Learning rate / motor skill acquisition (% per session) · capacity

1 1 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↓ -0.107 words per year, per additional year of baseline age per year Verbal learning: additional yearly decline per year of baseline age · Cognitively normal older adults (HELIAD), Greek Verbal Learning Test, ~3-year follow-up: additional yearly decrease in verbal learning for each additional year of age at baseline
ages mean 73.82 y · cognitively normal older adults, 761 with follow-up (1607 at baseline) · n = 761 · prospective cohort · Liampas I, et al. Clin Neuropsychol. 2023. PMID 35400289

Link to healthspan (1)

↑ ratio 2.22 (1.55 to 3.16) Low RAVLT total learning (trials 1-5) and progression to MCI or dementia → progression to MCI or dementia · Scoring 1 SD below the mean on RAVLT 1-5 at baseline; Cox HR
older adults with subjective cognitive decline (Czech Brain Aging Study) · n = 131 · prospective cohort · Jester DJ, et al. J Alzheimers Dis. 2022;86(4):1763-1774. PMID 35253751

Remedy and magnitude (3)

↑ SMD 0.31 (0.08 to 0.54) Cognitive training, immediate verbal memory (MS) · Cochrane meta-analysis in multiple sclerosis: cognitive training combined with other neuropsychological rehabilitation, immediate verbal memory
people with MS, mean age 44.6 y, 20 studies · n = 986 · meta analysis · Rosti-Otajarvi EM, et al. Cochrane Database Syst Rev. 2014. PMID 24515630
↑ SMD 0.71 (0.65 to 0.76) Simulation-based medical education with deliberate practice, clinical skill acquisition · Meta-analysis 1990-2010: SBME with deliberate practice vs traditional clinical education on skill acquisition outcomes
medical trainees, 14 studies · meta analysis · McGaghie WC, et al. Acad Med. 2011. PMID 21512370
↑ 0.66 Expertise Score points (0.55 to 0.77) AI tutoring feedback, simulated surgical skill acquisition · Virtual Operative Assistant feedback vs remote expert instruction: improvement in practice Expertise Score (range -1 to 1) during a single 75-minute simulation session; vs control 0.65 (0.54-0.77)
5 feedback sessions of 5 min within a single 75-min training · medical students, mean age 21.8 y, 4 Canadian institutions · n = 70 · rct · Fazlollahi AM, et al. JAMA Netw Open. 2022. PMID 35191972

Verbal fluency Category fluency (animals, 60 s) (words) · capacity

2 4 4

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↓ -0.081 SD per year (difference in slope) per year (-0.153 to -0.008) Coronary artery calcification score >=400: faster semantic fluency decline · BRAVE cohort: annual change in semantic fluency z-score, CAC >=400 vs CAC = 0
ages 40-80 (mean 60.0 y) · Beijing adults aged 40-80 (BRAVE) · n = 932 · prospective cohort · Liang J, et al. J Am Heart Assoc. 2024. PMID 39494555
↓ -0.065 SD per year (difference in slope) per year (-0.112 to -0.017) Highest tertile carotid intima-media thickness: faster semantic fluency decline · BRAVE cohort, adults 40-80 free of dementia, 2019 to 2022-2023: annual change in semantic fluency z-score, highest vs lowest cIMT tertile
ages 40-80 (mean 60.0 y) · Beijing adults aged 40-80 (BRAVE) · n = 932 · prospective cohort · Liang J, et al. J Am Heart Assoc. 2024. PMID 39494555

Link to healthspan (4)

↓ ratio 0.89 (0.81 to 0.97) Verbal fluency score and recurrent falls → recurrent falls · OR for being a recurrent faller per unit higher verbal fluency score (multinomial logistic regression)
community-dwelling older Brazilians · n = 230 · cross sectional · Fallaci IV, et al. Sao Paulo Med J. 2022;140(3):422-429. PMID 35507999
↓ ratio 0.64 (0.42 to 0.97) Animal Naming Test and frailty (Framingham) → frailty · Odds of Liver Frailty Index >= 4.5 per unit of Animal Naming Test (unit not stated in abstract)
ages median 70 · Framingham Heart Study participants without cirrhosis · n = 1,208 · cross sectional · Mehta M, et al. Am J Med. 2021;134(12):1530-1538. PMID 34464599
↓ ratio 0.71 (0.63 to 0.8) Better semantic fluency and mortality in memory-clinic patients → all-cause mortality · HR per unit of age-, sex- and education-adjusted semantic fluency Z score
ages mean 68.9 · memory clinic patients (CERAD-NAB registry) · n = 583 · prospective cohort · Frings L, et al. Alzheimers Res Ther. 2026;18(1). PMID 42571023
↑ ratio 1.31 (1.13 to 1.51) Animal Naming < 10 and ADL disability (HRS) → ADL disability · S-ANT1 < 10 (age- and education-adjusted animal naming) vs >= 10
ages mean 75 · older US adults (Health and Retirement Study 2010-2016) · n = 6,661 · prospective cohort · Tapper EB, et al. Clin Transl Gastroenterol. 2022;13(1):e00447. PMID 35080516

Remedy and magnitude (4)

↓ SMD -0.56 Deep brain stimulation (STN/GPi), phonemic verbal fluency (Parkinson's disease, 1-3 years) · Meta-analysis of long-term (1-3 year) neuropsychological outcomes after DBS in PD: phonemic verbal fluency decline
subthalamic nucleus or globus pallidus internus DBS, 1-3 year follow-up · adults with PD undergoing DBS, 48 studies (plus 271 PD controls) · n = 2,039 · meta analysis · Bucur M, et al. Neuropsychol Rev. 2023. PMID 35318587
↑ SMD 0.52 (0.23 to 0.81) Cognitive training, verbal semantic fluency (mild to moderate dementia) · Cochrane review: cognitive training vs control at end of treatment, verbal semantic fluency; gains retained 3-12 months post treatment
interventions 2-104 weeks long · people with mild to moderate dementia, 33 RCTs (12-653 participants each) · meta analysis · Bahar-Fuchs A, et al. Cochrane Database Syst Rev. 2019. PMID 30909318
↑ SMD 0.34 (0.01 to 0.66) Physiotherapy intervention, verbal fluency (Alzheimer's disease) · Meta-analysis of randomized and non-randomized controlled trials of physiotherapy in AD, verbal fluency
Alzheimer's disease, 23 trials · meta analysis · Zhu XC, et al. J Alzheimers Dis. 2015. PMID 25201787
↑ 11.6% Treadmill training with virtual reality, verbal fluency (MS) · Group-specific increase in verbal fluency after treadmill training plus VR in people with multiple sclerosis (p = 0.002)
6 wk · 3 sessions/week for 6 weeks · people with multiple sclerosis · n = 124 · rct · Galperin I, et al. J Neurol. 2023. PMID 36357586

Emotional

Emotional stability Affect variability / neuroticism (SD of daily affect; scale) · capacity

1 2 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↓ SMD -0.11 (-0.16 to -0.05) Neuroticism, age 24 to age 42 (population cohort) · Within-person standardised mean change in NEO-FFI neuroticism (inverse of emotional stability) between age 24 and age 42, whole cohort; negative = lower neuroticism, i.e. greater emotional stability
ages 24 to 42 y · Victorian Adolescent Health Cohort Study, general population (Australia) · n = 1,943 · prospective cohort · Kerr JA, et al. Sci Rep. 2026. PMID 42289456

Link to healthspan (2)

↑ ratio 1.82 (1.59 to 2.08) Neuroticism and incident Parkinson's disease (meta-analysis of prospective cohorts) → Parkinson's disease · Random-effects meta-analysis of four prospective studies (N = 548,284), follow-up one to four decades; HR for neuroticism (per-unit scaling not stated)
adults in four prospective cohorts · n = 548,284 · meta analysis · Terracciano A, et al. Mov Disord. 2021. PMID 33817817
↑ ratio 1.28 (1.21 to 1.36) Neuroticism and incident Parkinson's disease (UK Biobank) → Parkinson's disease · HR per unit of continuous neuroticism score (scaling not stated in abstract); top vs bottom quartile HR 1.88 (95% CI 1.60-2.22); 1142 incident PD cases over 11.91 years (mean 8.88 years)
UK Biobank adults, neuroticism scale completed 2006-2010 · n = 490,755 · prospective cohort · Terracciano A, et al. Mov Disord. 2021. PMID 33817817

Remedy and magnitude (3)

↑ SMD 0.82 Psychotherapy emotion-regulation methods (affect-focused and skills training) · Average pre- to post-treatment effect on emotion-regulation measures across 26 studies
psychotherapy patients (38 studies in meta-analysis, 26 pooled) · meta analysis · Iwakabe S, et al. Psychother Res. 2023. PMID 36943017
↑ SMD 0.37 Clinical and non-clinical interventions (personality trait change) · Change in personality trait measures across 207 intervention studies over an average of 24 weeks; emotional stability was the trait domain showing the most change, followed by extraversion
24 wk · mostly clinical intervention samples; 207 studies · meta analysis · Roberts BW, et al. Psychol Bull. 2017. PMID 28054797
↓ SMD -0.83 (-1.43 to -0.22) Dialectical behaviour therapy vs treatment as usual (borderline personality disorder): anger · Pooled SMD for anger, two RCTs, n = 46, I2 = 0%
adults with borderline personality disorder · n = 46 · meta analysis · Stoffers JM, et al. Cochrane Database Syst Rev. 2012. PMID 22895952

Stress reactivity Cortisol / HR response to acute stressor (nmol/L; beats/min) · capacity

3 2 2

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (3)

↑ SMD 0.42 (0.26 to 0.57) Cortisol response to challenge, older vs younger adults · Cohen's d for larger cortisol response to pharmacological or psychological challenge (or less suppression) in older (mean 69 y) vs younger (mean 28 y) healthy subjects; 45 parallel-group studies
ages older (69 +/- 6 y) vs younger (28 +/- 5 y) · healthy volunteers (670 younger, 625 older) · n = 1,295 · meta analysis · Otte C, et al. Psychoneuroendocrinology. 2005. PMID 15358445
↑ SMD 0.24 (0.02 to 0.47) Cortisol response to challenge, older vs younger men · Cohen's d, older vs younger men
ages older vs younger adults · healthy men · meta analysis · Otte C, et al. Psychoneuroendocrinology. 2005. PMID 15358445
↑ SMD 0.65 (0.34 to 0.97) Cortisol response to challenge, older vs younger women · Cohen's d, older vs younger women; effect of age on cortisol release stronger in women than men
ages older vs younger adults · healthy women · meta analysis · Otte C, et al. Psychoneuroendocrinology. 2005. PMID 15358445

Link to healthspan (2)

↓ ratio 3.5 (1.3 to 9.7) Blunted cortisol response to TSST and severe musculoskeletal pain with increased pressure-pain sensitivity (females) → musculoskeletal pain with increased pain sensitivity · Hyporesponse vs intermediate-response cluster; OR for more severe musculoskeletal pain at 22 when pressure pain threshold was below the median
ages 18-22 · Raine Study young adults, 45% female · n = 805 · prospective cohort · Paananen M, et al. Arthritis Res Ther. 2015. PMID 26654189
↓ ratio 2.3 (1 to 5) Blunted cortisol response to TSST at 18 and musculoskeletal pain at 22 (females) → musculoskeletal pain · Hyporesponse cluster (34% of females) vs intermediate-response cluster; adjusted OR for any musculoskeletal pain at age 22; Raine Study
ages 18-22 · Western Australian Pregnancy (Raine) Study young adults, 45% female · n = 805 · prospective cohort · Paananen M, et al. Arthritis Res Ther. 2015. PMID 26654189

Remedy and magnitude (2)

↓ -32% Compassion-based mental training (Affect module, 3 months), cortisol reactivity · Reduction in baseline-to-peak cortisol increase to the Trier Social Stress Test after 3-month Affect (compassion) training, vs no-training group
3 months of daily contemplative practice (Affect module) · healthy adults (ReSource Project) · n = 313 · rct · Engert V, et al. Sci Adv. 2017. PMID 28983508
↓ -51% Socio-cognitive mental training (Presence then Perspective), cortisol reactivity · Reduction in baseline-to-peak cortisol increase to the Trier Social Stress Test after 3-month Presence then 3-month Perspective (perspective-taking, contemplative dyads) training, vs no-training group
6 months of daily contemplative practice (Presence module then Perspective module) · healthy adults (ReSource Project) · n = 313 · rct · Engert V, et al. Sci Adv. 2017. PMID 28983508

Resilience Resilience scale (CD-RISC, BRS) (score) · capacity

3 3 2

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (3)

↑ 7.77 CD-RISC score points (1.97 to 13.57) CD-RISC, physicians over 60 vs 40 or younger · Adjusted mean CD-RISC difference, age >60 vs <=40 y, Canadian palliative care physicians
ages >60 y vs <=40 y · palliative care physicians (Canada) · n = 165 · cross sectional · Wang C, et al. BMC Palliat Care. 2020. PMID 33158428
↓ 0.22 BRS score points Brief Resilience Scale, 25-34 y vs 65-74 y · BRS mean 0.22 points higher in 25-34 y than 65-74 y (Cohen's d 0.273), German general-population norms
ages 25-34 y vs 65-74 y · representative German general population (2022 survey) · n = 2,522 · normative study · Rosner C, et al. BMC Psychol. 2024. PMID 39334458
↓ 0.26 BRS score points Brief Resilience Scale, 25-34 y vs 75+ y · BRS mean 0.26 points higher in 25-34 y than in those older than 75 y (Cohen's d 0.321)
ages 25-34 y vs >75 y · representative German general population (2022 survey) · n = 2,522 · normative study · Rosner C, et al. BMC Psychol. 2024. PMID 39334458

Link to healthspan (3)

↑ r = 0.43 (0.39 to 0.48) Resilience (Wagnild & Young Resilience Scale) and self-reported mental health in the somatically ill → mental health (self-reported) · Weighted mean Pearson correlation, random-effects model, 55 studies; I2 = 89.6%
patients with a somatic illness or health problem · n = 15,003 · meta analysis · Farber F, et al. Dtsch Arztebl Int. 2018. PMID 30373706
↑ ratio 1.28 (1.05 to 1.57) Baseline psychological resilience (CD-RISC-25) and frailty improvement over 3 years → frailty improvement · Adjusted OR for frailty improvement (Chinese Frailty Screening Scale-10) per unit CD-RISC (scaling not stated); community cohort Shanghai 2020-2023, age 60+
ages 60+ (mean 71.0) · community-dwelling older adults, Shanghai; 56.0% women · n = 4,033 · prospective cohort · Ye B, et al. JAMA Netw Open. 2024. PMID 39585692
↑ ratio 0.74 (0.69 to 0.8) Change in psychological resilience (delta CD-RISC) and frailty deterioration over 3 years → frailty deterioration · Adjusted OR for frailty deterioration per unit increase in CD-RISC between baseline and 3-year follow-up (scaling not stated); the matching OR for frailty improvement was 1.30 (95% CI 1.19-1.42)
ages 60+ (mean 71.0) · community-dwelling older adults, Shanghai · n = 4,033 · prospective cohort · Ye B, et al. JAMA Netw Open. 2024. PMID 39585692

Remedy and magnitude (2)

↑ SMD 0.194 (0.018 to 0.369) Resilience-enhancing interventions in forcibly displaced children (non-clinical settings) · Pooled Hedges g for resilience across 23 studies (8 RCTs, remainder non-randomised pre-post); interventions diverse, typically group-based
forcibly displaced children and adolescents · meta analysis · Thabet A, et al. BMJ Glob Health. 2023. PMID 36731918
↑ SMD 0.44 (0.23 to 0.64) Resilience training programmes (CBT-based, mindfulness-based or mixed) · Pooled effect of resilience interventions on validated resilience measures, random-effects meta-analysis of 11 RCTs
controlled trials of resilience interventions (17 included, 11 meta-analysed) · meta analysis · Joyce S, et al. BMJ Open. 2018. PMID 29903782

Depressive symptoms PHQ-9 / CES-D (score) · capacity

0 3 7

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (0)

no quantified finding yet

Link to healthspan (3)

↑ ratio 2.56 (1.62 to 4.04) Consistently high depressive-symptom trajectory (CES-D) and incident stroke → stroke · Adjusted OR for 'consistently high' vs 'no' depressive-symptom trajectory, CHARLS (n = 7792, 133 strokes); the same comparison gave OR 2.96 (95% CI 1.28-6.84) in ELSA and OR 1.56 (95% CI 1.03-2.36) in HRS
older adults, CHARLS (stroke by medical record linkage); HRS and ELSA by self-reported physician diagnosis · n = 7,792 · prospective cohort · Zhao Z, et al. Int J Surg. 2026. PMID 41208802
↑ ratio 1.54 (1.31 to 1.8) Escalating depressive symptoms with stable prefrailty and incident dementia → dementia · HR for trajectory group 3 ('stable prefrailty with escalating depressive symptoms') vs group 1 (stable robust, non-depressed); 10-year multitrajectories, HRS 1996-2018
Health and Retirement Study participants · n = 8,600 · prospective cohort · Hu C, et al. J Cachexia Sarcopenia Muscle. 2025. PMID 40189221
↑ ratio 1.86 (1.48 to 2.33) High and escalating frailty with persistent depression and incident dementia → dementia · HR for trajectory group 5 ('high and escalating frailty with persistent depression') vs group 1 (stable robust, non-depressed); HRS 1996-2018
Health and Retirement Study participants · n = 8,600 · prospective cohort · Hu C, et al. J Cachexia Sarcopenia Muscle. 2025. PMID 40189221

Remedy and magnitude (7)

↓ SMD -0.52 (-0.8 to -0.24) Postpartum exercise-only interventions vs no exercise · Pooled SMD for postpartum depressive-symptom severity, 19 RCTs; odds of postpartum depression OR 0.55 (95% CI 0.32-0.95, 4 RCTs, n = 303); at least a moderate reduction needed >= 350 MET-min/week
>= 350 MET-min/week (e.g. 80 min/week moderate intensity) for at least a moderate effect · postpartum people; 35 studies total (n = 4072) · n = 1,778 · meta analysis · Deprato A, et al. Br J Sports Med. 2025. PMID 39500542
↓ SMD -0.946 (-1.18 to -0.71) Exercise (aerobic and/or resistance) vs non-active control · Pooled SMD post-intervention, 41 RCTs, adults with MDD or elevated depressive symptoms; NNT = 2 (95% CI 1.68-2.59). Low-risk-of-bias subset SMD -0.666 (95% CI -0.99 to -0.34, k = 12)
adults 18+ with major depressive disorder or screen-positive depressive symptoms · n = 2,264 · meta analysis · Heissel A, et al. Br J Sports Med. 2023. PMID 36731907
↓ SMD 0.66 (0.48 to 0.83) Resistance exercise training vs non-active control · Mean Hedges d across 54 effects from 33 RCTs; NNT = 4; I2 = 76.0%
adults randomised to RET (n = 947) or non-active control (n = 930) · n = 1,877 · meta analysis · Gordon BR, et al. JAMA Psychiatry. 2018. PMID 29800984
↓ -1.1 PHQ-9 points (-1.9 to -0.2) Yoga vs strengthening exercise, 12 weeks (knee osteoarthritis) · Between-group difference in PHQ-9 change at 12 weeks (secondary outcome; 7 of 27 secondary outcomes favoured yoga)
12 wk · 2 supervised + 1 home session/week · adults 40+ with knee osteoarthritis, Tasmania; mean age 62.5, 72.6% female · n = 117 · rct · Abafita BJ, et al. JAMA Netw Open. 2025. PMID 40198073
↓ SMD 1.01 (0.44 to 1.57) Guidelines-based resistance exercise training, 8 weeks (young adults) · Twice-weekly one-on-one RET vs wait-list; Hedges d for change in QIDS depressive symptoms, total sample; analogue MDD subsample d = 1.71 (95% CI 0.96-2.46)
8 wk · 2 sessions/week, supervised one-on-one · young adults (26 +/- 5 y; 36 female) with and without analogue GAD/MDD · n = 55 · rct · O'Sullivan D, et al. Psychiatry Res. 2023. PMID 37429171
↓ -2.75 HADS-D points (-3.17 to -1.35) Mindfulness yoga vs stretching and resistance training, 8 weeks (Parkinson disease) · Time-by-group difference in HADS depression score at week 8 (T1); maintained at week 20 (beta -2.75, 95% CI -3.71 to -1.79)
8 wk · 90-minute group mindfulness yoga sessions (comparator 60-minute SRTE) · adults with mild-to-moderate idiopathic Parkinson disease, Hong Kong; mean age 63.7 · n = 138 · rct · Kwok JYY, et al. JAMA Neurol. 2019. PMID 30958514
↓ 47% Aerobic exercise at public-health dose (17.5 kcal/kg/week), 12 weeks (mild-moderate MDD) · Reduction in HRSD-17 score from baseline at 12 weeks: 47% for public-health dose vs 30% for low dose (7.0 kcal/kg/week) and 29% for flexibility-exercise placebo control; no effect of frequency (3 vs 5 days/week)
12 wk · 17.5 kcal/kg/week aerobic exercise, 3 or 5 days/week, supervised · adults 20-45 with mild to moderate major depressive disorder · n = 80 · rct · Dunn AL, et al. Am J Prev Med. 2005. PMID 15626549

Motor performance

Gait speed Usual gait speed (m/s) · capacity on the landscape

3 4 14

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, NHANES adults, 2017-2018 (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (3)

↓ r = -0.21 Correlation of gait speed with age, adults 20-79 · Comfortable and maximum gait speed both correlated with age (r >= -0.210, i.e. magnitude at least 0.21). Mean comfortable speed ranged from 127.2 cm/s (women in their seventies) to 146.2 cm/s (men in their forties); mean maximum speed from 174.9 cm/s (women in their seventies) to 253.3 cm/s (men in their twenties).
ages 20-79 · healthy volunteers aged 20-79 · n = 230 · normative study · Bohannon RW. Age Ageing. 1997. PMID 9143432
↓ -0.17 m/s Median, ages 40–59 vs 20–39 catalogue · 1.35 → 1.18 (-13%)
ages 40–59 vs 20–39 · NHANES adults, 2017-2018 · n = 2,780 · cross sectional · National Center for Health Statistics. National Health and Nutrition Examination Survey: 2017-2018 laboratory data. Hyattsville, MD: Centers for Disease Control and Prevention; 2020. doi 10.15620/cdc:106318
↓ -0.4 m/s Median, ages 60+ vs 20–39 catalogue · 1.35 → 0.95 (-30%)
ages 60+ vs 20–39 · NHANES adults, 2017-2018 · n = 2,820 · cross sectional · National Center for Health Statistics. National Health and Nutrition Examination Survey: 2017-2018 laboratory data. Hyattsville, MD: Centers for Disease Control and Prevention; 2020. doi 10.15620/cdc:106318

Link to healthspan (4)

↓ ratio 0.57 (0.48 to 0.66) Fastest vs slowest walking-speed category and all-cause mortality → all-cause mortality · HR for the fastest walking-speed category compared with the slowest (43% lower risk).
adults in 13 cohort studies · n = 530,841 · meta analysis · Liu Y, et al. J Sports Sci. 2024. PMID 39133765
↓ ratio 0.94 (0.92 to 0.96) Walking speed and all-cause mortality, per 0.1 m/s → all-cause mortality · HR per 0.1 m/s increment in walking speed (inverse linear dose-response; 6% lower risk per 0.1 m/s). Nonlinear above age 65.
adults in 11 cohort studies with dose-response data · n = 530,841 · meta analysis · Liu Y, et al. J Sports Sci. 2024. PMID 39133765
↑ ratio 1.32 (1.13 to 1.54) Slow gait speed (Fried criterion) and incident Parkinson disease → Parkinson disease · HR for the slow-gait-speed frailty component; 12-year follow-up of UK Biobank.
UK Biobank, mean age 56.1 · n = 314,998 · prospective cohort · Zheng Z, et al. JAMA Neurol. 2023. PMID 36912851
ratio 0.726 Pooled analysis of individual data from 9 cohort studies of community-dwelling older adult catalogue → mortality · per 1 SD
general · prospective cohort · Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50-58. PMID 21205966

Remedy and magnitude (14)

↑ 0.09 m/s (0.01 to 0.17) Strength training after stroke: fast-paced walking speed · Mean difference vs no exercise or usual care.
stroke survivors · n = 2,204 · meta analysis · Noguchi KS, et al. Br J Sports Med. 2025. PMID 39406459
↑ 0.05 m/s (0.02 to 0.09) Strength training after stroke: habitual walking speed · Mean difference vs no exercise or usual care; 42 RCTs; very low to moderate certainty.
stroke survivors · n = 2,204 · meta analysis · Noguchi KS, et al. Br J Sports Med. 2025. PMID 39406459
↑ 0.16 m/s Resistance plus balance exercise, with or without nutrition (sarcopenia) · Mean difference in usual gait speed vs usual care (moderate certainty); MID 0.1 m/s. Network meta-analysis of 42 RCTs.
12 wk · older adults with sarcopenia, median age 72.9 · n = 3,728 · meta analysis · Shen Y, et al. J Cachexia Sarcopenia Muscle. 2023. PMID 37057640
↑ SMD 0.26 Dual-task training in cognitive impairment · SMD for gait speed; 21 RCTs.
older adults with SCD, MCI, dementia or Alzheimer disease · n = 2,221 · meta analysis · Ali N, et al. J Prev Alzheimers Dis. 2022. PMID 35543010
↑ SMD 0.69 (0.29 to 1.09) Mixed training, resistance combined with balance/endurance/aerobic (sarcopenia) · SMD for gait speed vs control, I2 81%.
older people with sarcopenia, 26 studies · n = 1,191 · meta analysis · Lu L, et al. BMC Geriatr. 2021. PMID 34911483
↑ SMD 2.01 (1.04 to 2.97) Resistance training (sarcopenia) · SMD for gait speed vs control, fixed-effect model, I2 84%.
older people with sarcopenia, 26 studies · n = 1,191 · meta analysis · Lu L, et al. BMC Geriatr. 2021. PMID 34911483
SMD 0.12 (-0.15 to 0.39) Whole-body vibration training (sarcopenia) · SMD for gait speed vs control; not significant (p = 0.38).
older people with sarcopenia, 26 studies · n = 1,191 · meta analysis · Lu L, et al. BMC Geriatr. 2021. PMID 34911483
↑ 0.06 m/s (0.03 to 0.09) Treadmill training after stroke · Pooled mean difference in walking velocity vs other physiotherapy; 47 trials, 2323 participants, I2 44%, moderate quality. In participants independent in walking at baseline (38 studies, 1571 participants) MD 0.08 m/s (0.05-0.12).
people after stroke, average age 60 · n = 2,323 · meta analysis · Mehrholz J, et al. Cochrane Database Syst Rev. 2017. PMID 28815562
↑ 0.08 m/s (0.04 to 0.12) Progressive resistance strength training · Mean difference in gait speed vs control; 24 trials, 1179 participants.
two to three times per week, high intensity · older people · n = 1,179 · meta analysis · Liu CJ, et al. Cochrane Database Syst Rev. 2009. PMID 19588334
↑ 0.22 m/s Interventions for pre-frail and frail older adults (mostly exercise and multicomponent) · Reported gain in gait speed across trials with frailty improvements; 40 RCTs, 17,822 participants, mean age 68-79.
robust, pre-frail and frail adults 65+ · n = 17,822 · systematic review · Sobrinho ACDS, et al. Arch Gerontol Geriatr. 2025. PMID 40262339
↑ 0.16 m/s Resistance plus balance exercise (with or without nutrition) in older adults with sarcopenia catalogue · vs usual care
12 wk · older adults with sarcopenia, median age 73 (42 RCTs, 3728 participants) · meta analysis · Shen Y, Shi Q, Nong K, et al. Exercise for sarcopenia in older people: A systematic review and network meta-analysis. J Cachexia Sarcopenia Muscle. 2023. PMID 37057640
↑ 0.12 m/s (0.08 to 0.17) Motor-cognitive (dual-task) training in Parkinson's disease catalogue · vs control
people with Parkinson's disease, mean age 69 (11 studies, 597 people) · n = 597 · meta analysis · Johansson H, Folkerts AK, Hammarström I, et al. Effects of motor-cognitive training on dual-task performance in people with Parkinson's disease: a systematic re PMID 36820916
↑ 8.3% Individualized physiotherapy, 10 sessions over 14 days (Parkinson's disease) catalogue · vs active comparator (treadmill training)
25.0 min 10 sessions in 14 days, 14 days · patients with mild-to-moderate Parkinson's disease · rct · Gaßner H, Trutt E, Seifferth S, et al. Treadmill training and physiotherapy similarly improve dual task gait performance: a randomized-controlled trial in Parki PMID 35697942
↑ 0.19 m/s Low-intensity resistance training with blood flow restriction (stroke) catalogue · vs active comparator (high-intensity resistance training, 80% 1RM)
40.0 % 1RM · ischaemic stroke survivors · n = 16 · rct · Ahmed I, Mustafaoglu R, Erhan B. The effects of low-intensity resistance training with blood flow restriction versus traditional resistance exercise on lower ex PMID 37724785

Balance Single-leg stance / postural sway (s; mm) · capacity

4 1 7

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Centre-of-pressure path, bipedal stance, eyes closed, 10.4% per decade · the age range was not stated, so ages 30–80 are assumed.

Change with age (4)

↑ 10.4% per decade Centre-of-pressure path, bipedal stance, eyes closed · Amount of centre-of-pressure movement during quiet bipedal stance, eyes closed, increase per decade (both sexes)
ages >50 y · healthy adults over 50 · n = 40 · cross sectional · Rezaei A, et al. PLoS One. 2024. PMID 39441815
↑ 6.3% per decade Centre-of-pressure path, bipedal stance, eyes open · Amount of centre-of-pressure movement during quiet bipedal stance, eyes open, increase per decade (both sexes)
ages >50 y · healthy adults over 50 · n = 40 · cross sectional · Rezaei A, et al. PLoS One. 2024. PMID 39441815
↓ -0.53 SD per decade Unipedal stance duration, dominant leg · Change in z-scored single-leg stance time per decade, healthy adults over 50
ages >50 y · healthy adults over 50 · n = 40 · cross sectional · Rezaei A, et al. PLoS One. 2024. PMID 39441815
↓ -0.62 SD per decade Unipedal stance duration, non-dominant leg · Change in z-scored single-leg stance time per decade, healthy adults over 50
ages >50 y · healthy adults over 50 (Mayo Clinic, Rochester MN) · n = 40 · cross sectional · Rezaei A, et al. PLoS One. 2024. PMID 39441815

Link to healthspan (1)

↑ ratio 1.32 (1.1 to 1.59) Balance and mobility risk-factor domain and recurrent falls → recurrent falls · Summary relative risk for the balance-and-mobility domain (Lord classification) predicting recurrent falls (2+ per year); 22 prospective studies.
adults 60+ · meta analysis · Jehu DA, et al. Maturitas. 2021. PMID 33358204

Remedy and magnitude (7)

↑ SMD 0.64 (0.44 to 0.85) Vestibular rehabilitation after stroke: balance · Pooled SMD for balance; balance-specific training SMD 1.07 (0.70-1.45). 10 studies in meta-analysis.
late subacute and chronic stroke survivors, average age 60.9 · n = 413 · meta analysis · Nairn B, et al. J Am Heart Assoc. 2025. PMID 40407062
↑ 4.26 BBS points (1.82 to 6.69) Cognitive-motor dual-task training after stroke: Berg Balance Scale · Mean difference vs conventional single-task training; 17 RCTs; low-quality evidence.
hemiplegic stroke patients · n = 751 · meta analysis · Zhang L, et al. J Neuroeng Rehabil. 2024. PMID 39716165
↑ 3.77 BBS points (3.01 to 4.53) Exercise in multiple sclerosis: Berg Balance Scale · Weighted mean difference vs control; 40 RCTs (56 exercise groups n = 1300, 40 control groups n = 827).
people with multiple sclerosis · n = 2,127 · meta analysis · Du L, et al. Front Public Health. 2024. PMID 38660348
↑ SMD 0.51 (0.29 to 0.72) Virtual-reality exercise in chronic stroke: balance · SMD vs pooled controls; 43 RCTs; moderate GRADE.
adults with chronic stroke (>= 6 months) · n = 1,136 · meta analysis · Krohn M, et al. J Med Internet Res. 2024. PMID 39621381
↑ SMD 0.36 Dual-task training in cognitive impairment: balance · SMD for balance; 21 RCTs.
older adults with SCD, MCI, dementia or Alzheimer disease · n = 2,221 · meta analysis · Ali N, et al. J Prev Alzheimers Dis. 2022. PMID 35543010
↓ ratio 0.76 (0.7 to 0.81) Balance and functional exercise: rate of falls → falls · Rate ratio vs control, 39 studies, 7920 participants, high certainty (24% reduction). Multiple exercise types RaR 0.66 (0.50-0.88); Tai Chi RaR 0.81 (0.67-0.99).
community-dwelling people 60+, average age 76 · n = 7,920 · meta analysis · Sherrington C, et al. Cochrane Database Syst Rev. 2019. PMID 30703272
↓ ratio 0.747 (0.551 to 0.975) Home-based strength and balance exercise, age 80+ → falls · Risk ratio for falls vs usual routine (25.4% vs 44.3%); video-guided, remotely monitored.
52 wk · >= 3 sessions a week, >= 30 minutes per session · self-reliant adults 80+, mean age 84.4 · n = 124 · rct · Zhou J, et al. Ann Med. 2025. PMID 39918027

Fine motor control Purdue pegboard / finger tapping (pegs; taps/10 s) · capacity

2 3 2

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↓ 34% Finger-tapping frequency, 30s vs 80s · Finger-tapping frequency fell from 6.4 Hz (30s) to 4.2 Hz (80s), stated as 34%
ages 30-39 y vs 80-88 y · healthy adults 20-88 y, 10 per decade · n = 70 · cross sectional · Bowden JL, et al. Exp Gerontol. 2013. PMID 23570975
↑ 47% Grooved-pegboard completion time, 30s vs 80s · Grooved-pegboard time rose from 59 s (30s) to 111.5 s (80s) (medians), stated as 47%
ages 30-39 y vs 80-88 y · healthy adults 20-88 y, 10 per decade · n = 70 · cross sectional · Bowden JL, et al. Exp Gerontol. 2013. PMID 23570975

Link to healthspan (3)

↓ r = -0.25 Manual dexterity task time correlates with MMSE → global cognition (MMSE) · Simple correlation between time needed for the manual dexterity task and baseline MMSE score (longer time, lower MMSE)
ages older adults · community-dwelling older men and women, Progetto Veneto Anziani (Italy) · n = 2,361 · prospective cohort · Curreri C, et al. J Am Geriatr Soc. 2018. PMID 29322488
↑ ratio 2.2 (1.3 to 3.72) Slow manual dexterity task and incident cognitive impairment → cognitive impairment (incident) · OR for developing cognitive impairment (MMSE < 24) over mean 4.4-year follow-up, fourth (slowest) quartile of manual dexterity task time vs the rest, among subjects cognitively intact at baseline
ages older adults · community-dwelling older adults cognitively intact at baseline, Progetto Veneto Anziani (Italy) · n = 1,243 · prospective cohort · Curreri C, et al. J Am Geriatr Soc. 2018. PMID 29322488
↑ ratio 1.98 (1.42 to 2.76) Slow manual dexterity task and prevalent cognitive impairment → cognitive impairment (prevalent) · OR for cognitive impairment (MMSE < 24) at baseline, fourth (slowest) quartile of time needed to complete a manual dexterity task vs the rest; logistic regression
ages older adults · community-dwelling older men and women, Progetto Veneto Anziani (Italy) · n = 2,361 · prospective cohort · Curreri C, et al. J Am Geriatr Soc. 2018. PMID 29322488

Remedy and magnitude (2)

↑ 11.82% Routine physiotherapy (tennis elbow) · Within-group change in Purdue Pegboard dexterity after treatment vs before, control group receiving routine physiotherapy only
6 wk · adults with tennis elbow (14 males, 30 females) · n = 44 · rct · Mollazehi N, et al. J Bodyw Mov Ther. 2024. PMID 39593530
↑ 18.96% Routine physiotherapy plus proprioception exercises (tennis elbow) · Within-group change in Purdue Pegboard dexterity after treatment vs before, intervention group (routine physiotherapy plus proprioception exercises); control group (routine physiotherapy alone) 11.82%; no significant between-group difference
6 wk · 18 sessions within six weeks · adults with tennis elbow (14 males, 30 females) · n = 44 · rct · Mollazehi N, et al. J Bodyw Mov Ther. 2024. PMID 39593530

Dual-task performance Dual-task cost of gait (%) · capacity

2 3 8

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↑ SMD -0.474 (-0.871 to -0.078) Dual-task cost of gait speed with verbal fluency, older vs young · Hedges' g for the age difference in dual-task walking speed cost, verbal fluency tasks only
ages older vs young adults · healthy young and older adults, verbal-fluency studies (n = 8) · meta analysis · Harrison K, et al. Exp Brain Res. 2025. PMID 41045320
↑ SMD -0.261 (-0.491 to -0.031) Dual-task cost of gait speed, older vs young adults · Hedges' g for the age difference in dual-task walking speed cost; negative g = greater dual-task cost in older adults
ages older (mean 62-85 y) vs young (mean 20-31 y) · healthy young and older adults, 22 studies · n = 1,055 · meta analysis · Harrison K, et al. Exp Brain Res. 2025. PMID 41045320

Link to healthspan (3)

↑ ratio 1.018 (1.002 to 1.033) Dual-task stride-symmetry cost and future falls → falls · OR for falling over 2 years per additional percent of stride-symmetry dual-task cost
independent community-living adults >65 y without recent falls · n = 96 · prospective cohort · Gillain S, et al. Aging Clin Exp Res. 2019. PMID 31069697
↑ ratio 3.79 (1.57 to 9.15) High dual-task gait cost (counting backward) and incident dementia → dementia · HR for progression to dementia with high dual-task gait cost while counting backward, adjusted for age, sex, education, comorbidities and cognition
older adults with mild cognitive impairment (Gait and Brain Study) · n = 112 · prospective cohort · Montero-Odasso MM, et al. JAMA Neurol. 2017. PMID 28505243
↑ ratio 5.3 (3.1 to 9.1) Dual-task performance change and falls → falls · Pooled OR for falling when gait or attention-demanding task performance changed while dual tasking
older adults, 15 studies (retrospective and prospective) · systematic review · Beauchet O, et al. Eur J Neurol. 2009. PMID 19473368

Remedy and magnitude (8)

↓ -8.75 % (-14.57 to -2.92) Motor-cognitive training in Parkinson disease: dual-task cost on gait speed · Mean difference in dual-task cost vs controls; 11 studies; high certainty (GRADE).
people with Parkinson disease, mean age 68.9 · n = 597 · meta analysis · Johansson H, et al. J Neurol. 2023. PMID 36820916
↑ 0.12 m/s (0.08 to 0.17) Motor-cognitive training in Parkinson disease: dual-task gait speed · Mean difference vs controls; also dual-task cadence 2.91 steps/min (0.08-5.73) and stride length 10.12 cm (4.86-15.38).
people with Parkinson disease, mean age 68.9 · n = 597 · meta analysis · Johansson H, et al. J Neurol. 2023. PMID 36820916
↓ SMD 0.56 Dual-task training in cognitive impairment: dual-task cost · SMD for dual-task cost; 21 RCTs.
older adults with SCD, MCI, dementia or Alzheimer disease · n = 2,221 · meta analysis · Ali N, et al. J Prev Alzheimers Dis. 2022. PMID 35543010
↑ 8.3% Individualised physiotherapy in Parkinson disease: dual-task gait speed · Within-group improvement in dual-task gait speed; treadmill arm improved 4.2%.
2 wk · 10 individual 25-min sessions plus group therapy over 14 days · mild to moderate Parkinson disease · n = 105 · rct · Gassner H, et al. J Neural Transm. 2022. PMID 35697942
↑ 4.2% Treadmill training in Parkinson disease: dual-task gait speed · Within-group improvement in dual-task gait speed.
2 wk · 10 individual 25-min sessions plus group therapy over 14 days · mild to moderate Parkinson disease · n = 105 · rct · Gassner H, et al. J Neural Transm. 2022. PMID 35697942
↓ 9.5% Dual-task balance/mobility training after stroke: dual-task interference, forward walking · Reduction in dual-task interference on walking time, forward walking combined with verbal fluency (P = 0.014); with serial-3 subtraction 9.6% (P = 0.035).
8 wk · three 60-minute sessions per week · chronic stroke patients, age 61.2 +/- 6.4 · n = 84 · rct · Pang MYC, et al. Stroke. 2018. PMID 30571419
↓ 16.8% Dual-task balance/mobility training after stroke: dual-task interference, timed-up-and-go · Reduction in dual-task interference on timed-up-and-go combined with verbal fluency (P = 0.001).
8 wk · three 60-minute sessions per week · chronic stroke patients, age 61.2 +/- 6.4 · n = 84 · rct · Pang MYC, et al. Stroke. 2018. PMID 30571419
↓ 25% (3.1 to 46.9) Dual-task balance/mobility training after stroke: falls → falls · Reduction in risk of falls over 6-month follow-up vs controls; injurious falls reduced by 22.2% (4.0%-38.4%).
8 wk · three 60-minute sessions per week · chronic stroke patients, age 61.2 +/- 6.4 · n = 84 · rct · Pang MYC, et al. Stroke. 2018. PMID 30571419

Endurance 6-minute walk distance (m) · capacity

2 3 9

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: 6MWT distance decline per year of age (meta-regression), -10.25 m per year · the age range was not stated, so ages 30–80 are assumed.

Change with age (2)

↓ -10.25 m per year 6MWT distance decline per year of age (meta-regression) · Pooled mean distance fell from 587.43 m (age 60-64) to 325.53 m (age >= 80); meta-regression -10.25 m per year of age, +4.44 m per kg of weight. 28 studies.
ages 60+ · older adults, 28 studies · meta analysis · Otadi K, et al. Arch Gerontol Geriatr. 2026. PMID 41027267
↓ -5 m per year 6MWT reference equation, Portuguese adults · 6MWT = 226.93 - (5.00 x age) + (360.41 x height), R2 71%; age coefficient -5.00 m per year.
adult volunteers without disabilities, mean age 55.1 (SD 23.6) · n = 645 · normative study · Marques A, et al. Physiotherapy. 2020. PMID 32173042

Link to healthspan (3)

↑ ratio 1.646 6-minute walk distance and major adverse cardiovascular events → major adverse cardiovascular events · Adjusted HR per 100-m decrease in 6-minute walk distance
hypertrophic cardiomyopathy patients · n = 496 · prospective cohort · Zhang Y, et al. Can J Cardiol. 2025. PMID 40803520
↑ ratio 1.7 (1.2 to 2.5) 6-minute walk distance 290-338 m and all-cause mortality → mortality · HR for all-cause mortality, second-shortest distance quintile (290-338 m)
Cardiovascular Health Study participants without prevalent CVD · n = 1,665 · prospective cohort · Yazdanyar A, et al. J Aging Health. 2014. PMID 24695552
↑ ratio 2.1 (1.4 to 3) 6-minute walk distance below 290 m and all-cause mortality → mortality · HR for all-cause mortality, shortest distance quintile (<290 m), community-dwelling older adults without prevalent CVD
Cardiovascular Health Study participants without prevalent CVD · n = 1,665 · prospective cohort · Yazdanyar A, et al. J Aging Health. 2014. PMID 24695552

Remedy and magnitude (9)

↑ 18.6 m (2.29 to 34.92) HIIT vs moderate-intensity continuous training in coronary artery disease · Weighted mean difference in 6MWT favouring HIIT over MICT (active comparator); 22 studies, I2 0%.
coronary artery disease patients · n = 1,364 · meta analysis · Gao C, et al. PLoS One. 2025. PMID 39977401
↑ 25.56 m (16.34 to 34.79) Exercise in multiple sclerosis: 6MWT · Weighted mean difference vs control; 40 RCTs.
people with multiple sclerosis · n = 2,127 · meta analysis · Du L, et al. Front Public Health. 2024. PMID 38660348
↑ 64.46 m (14.6 to 114.32) Smoking cessation in COPD: 6MWT · Mean difference after cessation; I2 94%; 11 studies.
COPD patients who quit smoking · meta analysis · Wang Z, et al. Front Public Health. 2024. PMID 39722704
↑ 48.52 m (33.42 to 63.62) Exercise-based rehabilitation in pulmonary hypertension · Mean 6MWD higher than control; 11 studies, 418 participants, I2 72%, low certainty. Programmes lasted 3 to 25 weeks.
pulmonary hypertension, mean age 35-68 · n = 418 · meta analysis · Morris NR, et al. Cochrane Database Syst Rev. 2023. PMID 36947725
↑ 27.7 m (5.45 to 49.94) Breathing exercises in COPD: 6MWT · Mean difference vs control; 17 RCTs.
COPD patients · meta analysis · Yun R, et al. Can Respir J. 2021. PMID 33574969
↑ 21 m (1.57 to 40.4) Exercise-based cardiac rehabilitation in chronic heart failure · Improvement in 6MWT vs no-exercise control at 12 months (IPD meta-analysis, 19 RCTs).
52 wk · heart failure patients · n = 3,990 · meta analysis · Taylor RS, et al. Health Technol Assess. 2019. PMID 31140973
↑ 62 m (38 to 86) Pulmonary rehabilitation after COPD exacerbation · Mean improvement in 6MWD vs conventional care; high-quality evidence, I2 87%; 20 studies.
COPD patients after exacerbation · n = 1,477 · meta analysis · Puhan MA, et al. Cochrane Database Syst Rev. 2016. PMID 27930803
12.5 m (-17 to 42) HIIT vs MICT after stroke: 6MWD · Change in 6MWD: MICT 70.9 +/- 44.3 m vs HIIT 83.4 +/- 53.6 m; between-group mean difference 12.5 m, not significant (P = 0.401).
24 wk · poststroke gait dysfunction, mean age 62 · n = 47 · rct · Marzolini S, et al. J Am Heart Assoc. 2023. PMID 37947080
↑ 98 feet Supervised aerobic plus resistance training in CKD stages 3b-4 · Adjusted between-group difference in 6-minute walk distance over 12 months, reported in feet.
52 wk · adults 55+ with eGFR 15 to <45, mean age 68 · n = 99 · rct · Weiner DE, et al. Am J Kidney Dis. 2023. PMID 35944747

Sleep and recovery

Sleep efficiency Polysomnographic sleep efficiency / slow-wave sleep (%; min) · capacity

1 3 8

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↓ -0.6 % of sleep (SWS percentage points) per year Slow-wave sleep loss with ageing (repeated polysomnography) · Mean (SD) change in slow-wave sleep percentage across two overnight PSG studies a mean 5.2 years apart (range 4.8-7.1); Framingham Heart Study, age 60+
ages 60-87 (mean 69) · Framingham Heart Study participants 60+ without dementia at second PSG; 52% female · n = 346 · prospective cohort · Himali JJ, et al. JAMA Neurol. 2023. PMID 37902739

Link to healthspan (3)

↑ ratio 1.35 (1.1 to 1.66) Good sleep efficiency (> 85%) and good self-rated health → self-rated health · Adjusted OR for good self-rated health with self-reported sleep efficiency > 85% (sleep duration / time in bed), adjusted for comorbidity, depressive symptoms and cognitive difficulties; Lausanne cohort 65+
ages 66-75 · community-dwelling persons, Lausanne cohort 65+ · n = 2,712 · cross sectional · Simoes Maria M, et al. Eur Geriatr Med. 2020. PMID 32297231
↓ ratio 1.27 (1.06 to 1.54) Rate of slow-wave sleep loss and incident dementia → dementia · HR per each percentage-point decrease in SWS per year, Cox model adjusted for age, sex, cohort, APOE e4, smoking, sleeping-medication, antidepressant and anxiolytic use; 52 incident dementia cases over 17 years
ages 60-87 (mean 69) · Framingham Heart Study participants 60+ · n = 346 · prospective cohort · mechanism: SWS facilitates glymphatic clearance of proteins that aggregate in Alzheimer disease · Himali JJ, et al. JAMA Neurol. 2023. PMID 37902739
↑ 0.08 global cognition z-score per 1% sleep efficiency (0.03 to 0.14) Sleep maintenance efficiency and global cognition (Sleep and Dementia Consortium) → global cognition · Pooled beta for global cognitive composite z-score per 1% increase in PSG sleep maintenance efficiency, five US cohorts, neuropsychological assessment within 5 years of PSG; WASO beta per 1 min -0.07 (95% CI -0.13 to -0.01)
ages 58-89 (mean range across cohorts) · adults without stroke or dementia in ARIC, CHS, FHS, MrOS and SOF; 31.5% female · n = 5,946 · prospective cohort · Pase MP, et al. JAMA Netw Open. 2023. PMID 37462968

Remedy and magnitude (8)

↑ 15.59 % (sleep efficiency) (5.76 to 25.42) Yoga vs active control (insomnia), sleep-diary sleep efficiency · Network meta-analysis mean difference vs active controls (usual care, lifestyle modification); total sleep time +110.88 min (95% CI 58.66-163.09), WASO -55.91 min, sleep onset latency -29.27 min; low-certainty evidence for sleep efficiency
adults with insomnia, 22 RCTs, 13 interventions · n = 1,348 · meta analysis · Bu ZJ, et al. BMJ Evid Based Med. 2026. PMID 40664502
↑ SMD 0.77 (0.63 to 0.91) Cognitive behavioural therapy for insomnia in adults with chronic disease · Pooled Hedges g for sleep efficiency, 67 RCTs; insomnia severity g = 0.98 (95% CI 0.81-1.16), sleep onset latency g = 0.64 (95% CI 0.50-0.78); longer treatment gave better sleep-efficiency outcomes
adults 18+ with chronic disease (cancer, chronic pain, IBS, stroke) and insomnia · n = 5,232 · meta analysis · Scott AJ, et al. JAMA Intern Med. 2025. PMID 40982264
↑ 4.26 % (sleep efficiency) (1.26 to 7.26) Orexin antagonist (suvorexant/lemborexant) vs placebo, 4 weeks (mild-to-moderate Alzheimer disease) · Pooled mean difference in sleep efficiency, 2 studies; total nocturnal sleep time +28.2 min (95% CI 11.1-45.3) and WASO -15.7 min (95% CI -28.1 to -3.3) from one study (n = 274); moderate-certainty for TNST
4 wk · people with mild-to-moderate Alzheimer disease and sleep disturbance · n = 312 · meta analysis · McCleery J, et al. Cochrane Database Syst Rev. 2020. PMID 33189083
↑ 6.29 percentage points (sleep efficiency) (3.17 to 9.41) Tricyclic antidepressants (mainly low-dose doxepin) vs placebo (insomnia) · Pooled mean difference in sleep efficiency, 4 studies; sleep time +22.88 min (95% CI 13.17-32.59); subjective sleep quality SMD -0.39 (95% CI -0.56 to -0.21); moderate quality evidence
low-dose doxepin (5 of 6 TCA studies) · adults with primary diagnosis of insomnia · n = 510 · meta analysis · Everitt H, et al. Cochrane Database Syst Rev. 2018. PMID 29761479
↑ 3.5 % (sleep efficiency) (1.8 to 5.2) Conventional exercise vs no-intervention control, 12 weeks (older adults with chronic insomnia) · Adjusted mean difference in actigraphy sleep efficiency at post-intervention; WASO -17.0 min (95% CI -24.9 to -9.0); awakenings -2.8 (95% CI -4.0 to -1.6)
12 wk · 12-week conventional exercise programme · adults 60+ with chronic insomnia, Hong Kong · n = 320 · rct · Siu PM, et al. JAMA Netw Open. 2021. PMID 33587135
↑ 3.4 % (sleep efficiency) (1.6 to 5.1) Tai chi vs no-intervention control, 12 weeks (older adults with chronic insomnia) · Adjusted mean difference in actigraphy sleep efficiency at post-intervention; WASO -13.3 min (95% CI -21.3 to -5.2); awakenings -2.2 (95% CI -3.5 to -1.0); benefits maintained at 24-month follow-up
12 wk · 12-week tai chi training · adults 60+ with chronic insomnia, Hong Kong; mean age 67.3, 80% women · n = 320 · rct · Siu PM, et al. JAMA Netw Open. 2021. PMID 33587135
↑ 8 % (sleep efficiency) (6.6 to 9.5) Lemborexant 10 mg vs placebo, 1 month (insomnia disorder, 55+) · LSM treatment difference in PSG sleep efficiency change from baseline at nights 29-30; WASO -25.4 min (95% CI -31.4 to -19.3)
lemborexant 10 mg at bedtime for 1 month · adults 55+ with insomnia disorder, 67 sites · n = 1,006 · rct · mechanism: orexin receptor antagonism · Rosenberg R, et al. JAMA Netw Open. 2019. PMID 31880796
↑ 7.1 % (sleep efficiency) (5.6 to 8.5) Lemborexant 5 mg vs placebo, 1 month (insomnia disorder, 55+) · LSM treatment difference in PSG sleep efficiency change from baseline at nights 29-30; WASO -24.0 min (95% CI -30.0 to -18.0); SUNRISE 1 phase 3
lemborexant 5 mg at bedtime for 1 month · adults 55+ with insomnia disorder (sleep-maintenance difficulties), 67 sites; 86.4% women, median age 63 · n = 1,006 · rct · mechanism: orexin receptor antagonism · Rosenberg R, et al. JAMA Netw Open. 2019. PMID 31880796

Immune

Vaccine response Seroconversion / antibody titre (%; fold-rise) · capacity

3 4 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (3)

↓ SMD 1.4 (0.79 to 2.02) COVID-19 vaccine antibody titre, young vs older adults · SMD in geometric mean titre, young adults higher than older adults, five COVID-19 vaccines
ages young vs older adults · vaccine trial participants, 5 articles · meta analysis · mechanism: immunosenescence (authors' interpretation) · Wang J, et al. Front Immunol. 2021. PMID 34938287
↓ ratio 0.85 (0.76 to 0.94) Influenza A/H1N1 seroconversion, older vs younger adults · Pooled RR of seroconversion rate, adults >=60 y vs 18-60 y, inactivated quadrivalent influenza vaccine
ages >=60 y vs 18-60 y · RCT participants, older and younger adults (6 trials) · n = 7,976 · meta analysis · Meng Z, et al. Hum Vaccin Immunother. 2020. PMID 32347787
↓ ratio 0.77 (0.66 to 0.91) Influenza B/Victoria seroconversion, older vs younger adults · Pooled RR of seroconversion rate, adults >=60 y vs 18-60 y
ages >=60 y vs 18-60 y · RCT participants, older and younger adults (6 trials) · n = 7,976 · meta analysis · Meng Z, et al. Hum Vaccin Immunother. 2020. PMID 32347787

Link to healthspan (4)

↓ ratio 0.64 Hepatitis B vaccine response and all-cause mortality (dialysis) → mortality · Pooled RR of all-cause mortality, HBV vaccine responders (anti-HBs >10 mIU/mL) vs non-responders
dialysis patients, 61 studies · n = 6,628 · meta analysis · Udomkarnjananun S, et al. J Nephrol. 2020. PMID 31701375
↓ ratio 0.74 Hepatitis B vaccine response and cardiovascular mortality (dialysis) → cardiovascular mortality · Pooled RR of cardiovascular-related mortality, HBV vaccine responders vs non-responders
dialysis patients · n = 6,628 · meta analysis · Udomkarnjananun S, et al. J Nephrol. 2020. PMID 31701375
↓ ratio 0.72 (0.55 to 0.95) Seroconversion after hepatitis B vaccination and all-cause mortality (incident dialysis) → mortality · Adjusted HR for all-cause mortality, seroconversion (anti-HBs >=10 IU/L) vs non-response
incident dialysis patients (Austria) · n = 426 · prospective cohort · Zitt E, et al. Vaccine. 2017. PMID 28049587
↑ ratio 2.47 (1.38 to 4.43) Hepatitis B vaccine non-response and clinical AIDS or death (HIV) → clinical AIDS or death · Adjusted HR for clinical AIDS or death, non-response (anti-HBs <10 IU/L) vs response, adjusted for CD4, viral load, HAART and DTH response
HIV-infected adults vaccinated after HIV diagnosis · n = 795 · prospective cohort · Landrum ML, et al. PLoS One. 2012. PMID 22457767

Remedy and magnitude (3)

0.01 percentage points (-5 to 5.1) Fractional-dose (500 IU) vs standard-dose (13,803 IU) 17D-204 yellow fever vaccine: seroconversion at 28 days · Difference in incidence of seroconversion (>= 4-fold rise in plaque reduction neutralisation titre), intention-to-treat; per-protocol difference -1.8 percentage points (95% CI -6.7 to 3.2); standard-dose seroconversion 98% (95% CI 94-100); noninferiority margin -10 percentage points
4 wk · single dose 500 IU (vs 13,803 IU) · adults in Uganda and Kenya with no history of yellow fever vaccination or infection; 120 per group · n = 480 · rct · Kimathi D, et al. N Engl J Med. 2025. PMID 39970397
↓ ratio 0.21 (0.08 to 0.54) Fingolimod 0.5 mg vs placebo (relapsing MS): influenza vaccine responder rate · Responder rate (seroconversion or >= 4-fold titre rise to at least one strain) at 3 weeks post-vaccination: 54% fingolimod vs 85% placebo; OR fingolimod vs placebo. At 6 weeks 43% vs 75% (OR 0.25, 95% CI 0.11-0.57). Tetanus toxoid recall: 40% vs 61% (OR 0.43, 95% CI 0.20-0.92) at 3 weeks
12 wk · fingolimod 0.5 mg daily for 12 weeks; vaccination at week 6 · patients 18-55 with relapsing MS (fingolimod 95, placebo 43) · n = 138 · rct · Kappos L, et al. Neurology. 2015. PMID 25636714
↑ 20% mTOR inhibitor RAD001 (everolimus) before influenza vaccination (elderly) · Enhancement of influenza vaccine response 'by about 20%' at doses that were relatively well tolerated; also reduced percentage of PD-1-expressing CD4 and CD8 T cells
elderly volunteers · rct · mechanism: mTOR inhibition reduces PD-1 expression on T cells, which rises with age and inhibits T cell signalling · Mannick JB, et al. Sci Transl Med. 2014. PMID 25540326

Metabolic

Resting metabolic rate Resting energy expenditure (kcal/day) · capacity

3 3 4

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Total energy expenditure decline per decade, normal-weight adults, -150 kcal/day per decade.

Change with age (3)

↓ -150 kcal/day per decade Total energy expenditure decline per decade, normal-weight adults · TEE fell by approximately 150 kcal per decade across adult life (BMI 18.5-25.0); physical activity level fell from 1.75 (second decade) to 1.28 (ninth decade).
ages 20-100 · adults 20-100 in the US Institute of Medicine doubly-labelled-water database · meta analysis · Roberts SB, et al. Public Health Nutr. 2005. PMID 16277818
↓ -326 kJ/d per decade Resting metabolic rate decline per decade, men (GISELA cohort) · Linear mixed model, 12-year follow-up; after adjustment for body composition and fat distribution the decline was 286 kJ/d per decade.
ages mean initial age 66.9 · elderly German men · n = 153 · prospective cohort · Luhrmann PM, et al. Eur J Clin Nutr. 2009. PMID 19190667
↓ -158 kJ/d per decade Resting metabolic rate decline per decade, women (GISELA cohort) · Linear mixed model, 12-year follow-up; after adjustment for body composition and fat distribution the decline was 81 kJ/d per decade.
ages mean initial age 67.4 · elderly German women · n = 363 · prospective cohort · Luhrmann PM, et al. Eur J Clin Nutr. 2009. PMID 19190667

Link to healthspan (3)

↓ ratio 0.47 (0.23 to 0.96) Higher RMR and incident basic-ADL disability (pre-frail/frail) → disability (basic ADL) · Odds ratio for incident BADL disability over 10 years with higher RMR, pre-frail/frail stratum, fully adjusted.
adults 70+, FRADEA study, Spain · n = 298 · prospective cohort · Flores Ruano T, et al. Aging Clin Exp Res. 2023. PMID 36626043
↓ ratio 0.39 (0.18 to 0.84) Higher RMR and incident instrumental-ADL disability (pre-frail/frail) → disability (instrumental ADL) · Odds ratio for incident IADL disability over 10 years, pre-frail/frail stratum.
adults 70+, FRADEA study, Spain · n = 298 · prospective cohort · Flores Ruano T, et al. Aging Clin Exp Res. 2023. PMID 36626043
↓ ratio 0.3 (0.14 to 0.64) Higher RMR and mobility decline (pre-frail/frail) → mobility decline · Odds ratio for mobility decline (Functional Ambulation Categories) over 10 years, pre-frail/frail stratum.
adults 70+, FRADEA study, Spain · n = 298 · prospective cohort · Flores Ruano T, et al. Aging Clin Exp Res. 2023. PMID 36626043

Remedy and magnitude (4)

↑ 595.5 kJ/d (67 to 1,124) High-protein vs standard-protein energy-restricted low-fat diet: REE preserved · Weighted mean difference in REE change favouring the high-protein diet (mitigated reduction); 24 trials, mean duration 12.1 weeks.
12 wk · adults 18+ in weight-loss trials · n = 1,063 · meta analysis · Wycherley TP, et al. Am J Clin Nutr. 2012. PMID 23097268
↑ 11% Short-term endurance training in healthy elderly · RMR rose 11% (1,596 +/- 214 to 1,763 +/- 170 kcal/day, P < 0.01); VO2max rose 9%; total energy expenditure unchanged because activity outside training fell 62%.
healthy elderly volunteers aged 56-78 · n = 11 · prospective cohort · Goran MI, et al. Am J Physiol. 1992. PMID 1443128
-64 kcal/day (-129.3 to 1.4) Intranasal oxytocin in obesity: resting energy expenditure · Difference vs placebo in REE change (adjusted for lean mass) from baseline to week 8; not significant.
8 wk · 24 IU intranasal four times daily · adults with obesity, mean age 33.6 · n = 61 · rct · Plessow F, et al. NEJM Evid. 2024. PMID 38815173
↑ 209 kcal/d (91 to 326) Low- vs high-carbohydrate diet during weight-loss maintenance: total energy expenditure · Change in TEE (doubly labelled water) greater on the 20% carbohydrate diet than the 60% carbohydrate diet, intention-to-treat; linear trend 52 kcal/d (23-82) per 10% decrease in carbohydrate.
2 wk · 20% vs 60% of energy from carbohydrate, protein held constant · adults 18-65 with BMI >= 25 after 12% weight loss · n = 162 · rct · Ebbeling CB, et al. BMJ. 2018. PMID 30429127

Thermoregulation Sweat rate / core-temperature rise in heat (L/h; degrees C) · capacity

2 2 3

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (2)

↑ 0.11 degrees C Summer oral temperature, under-65 vs 65+ (Taipei) · Mean oral temperature of the <65 group was 0.11 degrees C lower than the >= 65 group in summer; no difference in winter. Correlation of oral with ambient temperature r = 0.48 in those >= 85 vs 0.31 (65-74) and 0.23 (75-84).
ages 20-64 vs 65-95 · 519 community-dwelling adults 65-95 and 540 adults 20-64 · n = 1,059 · cross sectional · Lu SH, et al. Int J Nurs Stud. 2009. PMID 19128801
↓ -0.17 degrees C (-0.3 to -0.03) Basal body temperature, older vs young adults (meta-analysis) · Older adults have lower body temperature than young adults (P = 0.04); core temperature -0.13 (-0.27; 0.01), skin temperature -0.21 (-0.5; 0.08). 16 studies.
ages older vs young adults · older and young adults, 16 studies · meta analysis · Hernandes Junior PR, et al. Curr Aging Sci. 2021. PMID 34886774

Link to healthspan (2)

↑ ratio 1.5 Fever after stroke or neurologic injury and mortality → mortality · Relative risk of death with fever/higher body temperature vs normothermia; 39 studies, 14431 subjects. Other RRs: Glasgow Outcome Scale 1.3, Barthel 1.9, modified Rankin 2.2, ICU stay 2.8, hospital stay 3.2.
patients with stroke and other brain injuries · n = 14,431 · meta analysis · Greer DM, et al. Stroke. 2008. PMID 18723420
↑ ratio 2.9 (1.9 to 4.2) Low spontaneous core temperature (<35 degrees C) after cardiac arrest and in-hospital death → in-hospital mortality · Adjusted odds ratio at initiation of hypothermia therapy; features suggestive of impaired thermoregulation.
adults after in- or out-of-hospital cardiac arrest · n = 597 · prospective cohort · Li A, et al. Can J Anaesth. 2024. PMID 38514524

Remedy and magnitude (3)

↑ 0.1 degrees C 35-day horizontal bedrest: exercise core-temperature rise · Bedrest potentiated the rectal-temperature elevation during 40-min cycling at a fixed absolute intensity (30% of pre-bedrest peak workload) by about 0.10 degrees C (P <= 0.05); mean skin temperature attenuated by about 1.5-2.0 degrees C; forehead sweating rate not modulated.
5 wk · 35 days horizontal bedrest · healthy men (10 bedrest, 5 control) · n = 15 · rct · mechanism: impairment in non-evaporative heat loss after cardiovascular and muscular deconditioning · Kounalakis SN, et al. Exp Physiol. 2021. PMID 33938053
↓ -0.16 degrees C Seasonal heat acclimatisation: resting core temperature · Reduction in resting core temperature after summer (2 studies, P < 0.05); mean summer WBGT 25.2 degrees C.
healthy adults, 29 studies, 8 countries · n = 561 · systematic review · Brown HA, et al. Sports Med. 2022. PMID 35460514
↑ 0.03 L/h (0.03 to 0.53) Seasonal heat acclimatisation: sweat rate · Increase in sweat rate after summer across 11 studies, range 0.03-0.53 L/h (P < 0.05); no pooled estimate.
healthy adults, 29 studies, 8 countries · n = 561 · systematic review · Brown HA, et al. Sports Med. 2022. PMID 35460514

Body composition and tissue

Visceral fat Visceral adipose tissue (MRI/CT/DXA) (cm2; kg) · physical parameter on the landscape

2 2 10

Trajectory with age: default, and given an intervention

Intervention starts at age 60

Default (no intervention)Given the selected intervention

Default: Catalogue median by age band, Peto et al. 2017 (MortalityPredictors.org) anchor cohort (bands 20-39, 40-59 and 60+ plotted at ages 30, 50 and 70).

Change with age (2)

↑ 0.434 kg Median, ages 40–59 vs 20–39 catalogue · 1.086 → 1.52 (+40%)
ages 40–59 vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 800,000 · cross sectional · Peto MV, et al. MortalityPredictors.org: a manually-curated database of published results from longitudinal studies of mortality risk factors. Aging (Albany NY). 2017;9(9):1965-1983. PMID 28858850
↑ 0.702 kg Median, ages 60+ vs 20–39 catalogue · 1.086 → 1.788 (+65%)
ages 60+ vs 20–39 · Peto et al. 2017 (MortalityPredictors.org) anchor cohort · n = 800,000 · cross sectional · Peto MV, et al. MortalityPredictors.org: a manually-curated database of published results from longitudinal studies of mortality risk factors. Aging (Albany NY). 2017;9(9):1965-1983. PMID 28858850

Link to healthspan (2)

↑ ratio 2.26 High MRI visceral adipose tissue z-score and incident diabetes → incident diabetes · HR up to 2.26 for incident diabetes, high VAT z-score category (z > 1) vs middle category (z -1 to 1), adjusted for cardiometabolic risk factors
UK Biobank and German National Cohort adults, mean age 57.7 y · n = 66,608 · prospective cohort · Jung M, et al. Radiology. 2026. PMID 42084507
ratio 1.46 (1.28 to 1.66) UK Biobank prospective cohort (n=502,631) catalogue → mortality · highest vs lowest tertile
general · n = 502,631 · prospective cohort · Peto MV, et al. MortalityPredictors.org: a manually-curated database of published results from longitudinal studies of mortality risk factors. Aging (Albany NY). 2017;9(9):1965-1983. PMID 28858850

Remedy and magnitude (10)

↓ SMD -0.49 (-0.87 to -0.11) Resistance training in healthy adults · Visceral fat change with full-body resistance training (at least 4 weeks) vs no-exercise control
healthy adults (58 studies in review, 54 in meta-analysis) · meta analysis · Wewege MA, et al. Sports Med. 2022. PMID 34536199
↓ -126 g (-179 to -73.3) Energy-reduced Mediterranean diet plus physical activity, 1 year · Between-group difference in visceral fat (DXA) at 1 year vs control (ad libitum Mediterranean diet, no activity promotion)
energy-reduced Mediterranean diet plus physical activity · adults 55-75 y with overweight/obesity and metabolic syndrome (PREDIMED-Plus subsample) · n = 1,521 · rct · Konieczna J, et al. JAMA Netw Open. 2023. PMID 37851444
↓ -70.4 g (-126 to -15.2) Energy-reduced Mediterranean diet plus physical activity, 3 years · Between-group difference in visceral fat (DXA) at 3 years vs control
energy-reduced Mediterranean diet plus physical activity · adults 55-75 y with overweight/obesity and metabolic syndrome (PREDIMED-Plus subsample) · n = 1,521 · rct · Konieczna J, et al. JAMA Netw Open. 2023. PMID 37851444
↓ -36% Weight loss plus aerobic and resistance exercise · Visceral adipose tissue (MRI) change at 6 months with ~10% matched weight loss plus combined aerobic and resistance exercise
combined aerobic + resistance exercise, 6 months, with weight loss · older adults with obesity · n = 160 · rct · Waters DL, et al. J Gerontol A Biol Sci Med Sci. 2022. PMID 33839788
↓ -19% Weight loss plus aerobic exercise · Visceral adipose tissue (MRI) change at 6 months with ~10% matched weight loss plus aerobic exercise
aerobic exercise, 6 months, with weight loss · older adults with obesity · n = 160 · rct · Waters DL, et al. J Gerontol A Biol Sci Med Sci. 2022. PMID 33839788
↓ -21% Weight loss plus resistance exercise · Visceral adipose tissue (MRI) change at 6 months with ~10% matched weight loss plus resistance exercise
resistance exercise, 6 months, with weight loss · older adults with obesity · n = 160 · rct · Waters DL, et al. J Gerontol A Biol Sci Med Sci. 2022. PMID 33839788
↓ -36% Combined aerobic + resistance exercise during 10% weight loss (older adults) catalogue · vs control (diet only)
6 months · obese older adults undergoing dieting · n = 160 · rct · Waters DL, Aguirre L, Gurney B, et al. J Gerontol A Biol Sci Med Sci. 2022. PMID 33839788
↓ -9.5% Caloric restriction (-390 kcal/day) catalogue · vs active (sitagliptin 100 mg/day, weight-neutral)
14 wk · 390.0 kcal deficit daily · adults with obesity and prediabetes · n = 88 · rct · Silver HJ, Olson D, Mayfield D, et al. Diabetes Obes Metab. 2023. PMID 37188932
↓ -4.8% Liraglutide 1.8 mg/day catalogue · vs active (sitagliptin 100 mg/day, weight-neutral)
14 wk · 1.8 mg daily · adults with obesity and prediabetes · n = 88 · rct · Silver HJ, Olson D, Mayfield D, et al. Diabetes Obes Metab. 2023. PMID 37188932
↓ -33.2% (-42.1 to -24.2) Semaglutide 2.4 mg once weekly catalogue · vs placebo
68 wk · 2.4 mg weekly · adults from Japan and South Korea with obesity, with or without T2D · n = 401 · rct · Kadowaki T, Isendahl J, Khalid U, et al. Lancet Diabetes Endocrinol. 2022. PMID 35131037

Liver fat Hepatic fat fraction (MRI-PDFF / MRS) (%) · physical parameter

1 3 5

No default trajectory with age yet for this item: there is no stored population distribution by age band and no per-year rate in the evidence.

Change with age (1)

↑ ratio 3 Postprandial hepatic triglyceride content, elderly vs young · Approximately threefold higher postprandial hepatic triglyceride content (13C/1H MRS) in healthy, normal-weight, sedentary elderly than pair-matched young subjects after two high-carbohydrate meals
ages elderly vs young (pair-matched) · healthy normal-weight sedentary elderly (73 +/- 2 y) and young (26 +/- 2 y) adults · n = 24 · cross sectional · mechanism: muscle insulin resistance diverts postprandial carbohydrate to hepatic de novo lipogenesis · Flannery C, et al. Diabetes. 2012. PMID 22829450

Link to healthspan (3)

↑ ratio 1.44 (1.27 to 1.63) Fatty liver index >=60 and all-cause mortality → mortality · HR for overall mortality, fatty liver index (FLI) >=60 vs <30
EPIC cohort random subsample · n = 15,784 · prospective cohort · Mayen AL, et al. BMC Med. 2024. PMID 38825687
↑ ratio 2.06 (1.61 to 2.63) Fatty liver index >=60 and cardiovascular mortality → cardiovascular mortality · HR for CVD death, fatty liver index (FLI) >=60 vs <30
EPIC cohort random subsample · n = 15,784 · prospective cohort · Mayen AL, et al. BMC Med. 2024. PMID 38825687
↑ ratio 1.35 Steatotic liver disease with metabolic dysfunction and all-cause mortality → mortality · HR for all-cause mortality in SLD with metabolic dysfunction vs without (liver fat score / fatty liver index)
Korean adults aged 19 y or older (KNHANES linked to death data) · n = 26,734 · prospective cohort · Han E, et al. Metabolism. 2024. PMID 38224909

Remedy and magnitude (5)

↓ -68.5% (-84.4 to -52.5) Pemvidutide 1.8 mg, liver fat content at 12 weeks · Relative reduction in liver fat content (MRI-PDFF) from baseline at week 12 with pemvidutide 1.8 mg, vs placebo 4.4%
12 wk · once-weekly subcutaneous 1.8 mg · MASLD with BMI >=28 kg/m2 and liver fat >=10% · n = 94 · rct · Harrison SA, et al. J Hepatol. 2025. PMID 39002641
↓ -82.4% Retatrutide 12 mg, liver fat at 24 weeks · Mean relative change from baseline in liver fat at 24 weeks with retatrutide 12 mg (placebo +0.3%); normal liver fat (<5%) in 86%
24 wk · once-weekly subcutaneous 12 mg · MASLD with liver fat >=10% and obesity · n = 98 · rct · Sanyal AJ, et al. Nat Med. 2024. PMID 38858523
↓ -5.48 % IHTG (-7.77 to -3.18) Alternate day fasting plus aerobic exercise, intrahepatic triglyceride · Change in intrahepatic triglyceride content at month 3 with ADF plus moderate-intensity aerobic exercise vs control (-0.17%)
ADF (600 kcal fast day alternated with ad libitum day) plus aerobic exercise 5 x 60 min/week, 3 months · adults with obesity and NAFLD · n = 80 · rct · Ezpeleta M, et al. Cell Metab. 2023. PMID 36549296
↓ -19.7% Saroglitazar 4 mg, liver fat content at 16 weeks · Least-squares mean percent change in MRI-PDFF liver fat content with saroglitazar 4 mg (placebo +4.1%)
16 wk · saroglitazar 4 mg daily · NAFLD/NASH with ALT >=50 U/L and BMI >=25 kg/m2 · n = 106 · rct · Gawrieh S, et al. Hepatology. 2021. PMID 33811367
↓ -22.5% (-32.9 to -12.2) Resmetirom 80 mg, hepatic fat at 12 weeks · Least-squares mean difference in relative change in MRI-PDFF hepatic fat vs placebo at week 12 (-32.9% resmetirom vs -10.4% placebo)
12 wk · 80 mg orally once daily · biopsy-confirmed NASH with hepatic fat fraction >=10% · rct · Harrison SA, et al. Lancet. 2019. PMID 31727409

Skin autofluorescence Skin autofluorescence (AGE reader) (AU) · physical parameter

3 3 1

Trajectory with age: default, and given an intervention

Default (no intervention)

Default: Skin autofluorescence reference slope, men, 0.019 AU per year.

Change with age (3)

↑ 0.019 AU per year Skin autofluorescence reference slope, men · Predicted SAF = 0.0191 x age + 1.038 in healthy never-smoking men (BMI <35, no metabolic syndrome); slope per year
ages 18-70 y · healthy never-smoking men, Lifelines cohort · n = 8,179 · cross sectional · Wolffenbuttel BHR, et al. Front Endocrinol. 2025. PMID 41282282
↑ 0.019 AU per year Skin autofluorescence reference slope, women · Predicted SAF = 0.0188 x age + 0.994 in healthy never-smoking women (BMI <35, no metabolic syndrome); slope per year
ages 18-70 y · healthy never-smoking women, Lifelines cohort · n = 7,930 · cross sectional · Wolffenbuttel BHR, et al. Front Endocrinol. 2025. PMID 41282282
↑ 0.023 AU per year Skin autofluorescence, linear increase with age (to 70 y) · Linear increase of approximately 0.023 AU per year up to age 70 in healthy Caucasian controls (AGE Reader and predecessor)
ages up to 70 y · healthy Caucasian control subjects · n = 428 · cross sectional · Koetsier M, et al. Diabetes Technol Ther. 2010. PMID 20388050

Link to healthspan (3)

↑ ratio 1.91 (1.42 to 2.56) Higher skin autofluorescence and all-cause mortality → mortality · Pooled HR for all-cause mortality with higher SAF (random effects, 10 observational studies)
patients at high and very high cardiovascular risk · meta analysis · Cavero-Redondo I, et al. J Am Heart Assoc. 2018. PMID 30371199
↑ ratio 2.06 (1.58 to 2.67) Higher skin autofluorescence and cardiovascular mortality → cardiovascular mortality · Pooled HR for cardiovascular mortality with higher SAF (random effects, 10 observational studies)
patients at high and very high cardiovascular risk · meta analysis · Cavero-Redondo I, et al. J Am Heart Assoc. 2018. PMID 30371199
↑ ratio 1.21 (1.01 to 1.46) Skin autofluorescence per SD and dementia → dementia · HR for incident dementia per standard deviation higher skin autofluorescence, independent of age and other confounders
Rotterdam Study participants without dementia, mean age 72.6 y · n = 2,922 · prospective cohort · Mooldijk SS, et al. Sci Rep. 2024. PMID 38218902

Remedy and magnitude (1)

0 SAF (AGE Reader fluorescence ratio, 420-600 nm / 300-420 nm) Equol-containing supplement, 12 weeks (null) · Median within-arm change in skin autofluorescence after 12 weeks: equol 0, control 0.05; between-group p = 0.13
12 wk · equol-containing supplement daily · postmenopausal Japanese women · n = 57 · rct · Yoshikata R, et al. PLoS One. 2021. PMID 34506596

Every biomarker, in the same layout

The age difference is the cross-sectional difference between the median for adults 60 and over and adults 20–39 in the catalogue's population distribution (NHANES for some biomarkers, other named cohorts and reference studies for the rest), a stored value, not within-person change. The hazard ratio is from the published cohort with the most information; the remedy count and the largest percentage effect come from the intervention catalogue. Open a biomarker for the full set.

Biomarker	Category	Median, 60+ vs 20–39	Mortality hazard ratio	Remedies catalogued
8-Hydroxy-2'-deoxyguanosine (8-OHdG)	Oxidative Stress	3.588 → 4.251 (+18%) ng/mg creatinine	1.1 (1.01–1.2) per 1 SD	3 · nutraceutical, pharmacologic
Abdominal Aortic Calcification (AAC)	Cardiac & Hemodynamics	1.84 → 2.18 (+18%) severity score	1.37 (1.15–1.64) highest vs lowest quartile	—
Absolute Lymphocyte Count	Hematology	2.042 → 2.136 (+5%) 10^3 cells/uL	1.35 (1.22–1.5) highest vs lowest tertile	1 · pharmacologic
Absolute Neutrophil Count	Hematology	3.514 → 4.622 (+32%) 10^3 cells/uL	1.32 (1.2–1.45) highest vs lowest tertile	—
Adiponectin	Vitamins & Endocrine	10.58 → 12.54 (+18%) ug/mL	1.24 (1.17–1.31) per 1 SD	3 · pharmacologic, diet
Aerobic capacity	Cardiorespiratory	42 → 28.5 (-32%) mL/kg/min	0.49 (0.42–0.57) highest vs lowest tertile	7 · exercise, lifestyle, clinical_procedure
Alanine Aminotransferase (ALT)	Liver & Nutritional	19 → 18 (-5%) U/L	1.26 (1.12–1.42) highest vs lowest quartile	8 · diet, pharmacologic, supplement
Albumin-Adjusted Anion Gap	Electrolytes & Minerals	8.28 → 9.81 (+18%) mEq/L	1.77 (1.24–2.52) highest vs lowest quartile	—
Albumin:Globulin Ratio (A/G)	Liver & Nutritional	1.352 → 1.602 (+18%) ratio	0.75 (–) per 1 SD	—
Alkaline Phosphatase (ALP)	Liver & Nutritional	65 → 79 (+22%) U/L	1.38 (1.25–1.52) highest vs lowest tertile	8 · pharmacologic, nutraceutical, clinical_procedure
Alpha-1-Antichymotrypsin (AACT)	Inflammation	142.6 → 168.9 (+18%) mg/dL	1.21 (1.11–1.33) per 1 SD	1 · supplement
Alpha-1-Antitrypsin (AAT)	Inflammation	174.8 → 207.1 (+18%) mg/dL	2.12 (1.41–3.18) highest vs lowest quartile	1 · pharmacologic
Alpha-1-Microglobulin	Renal & Purine	18.22 → 25.72 (+41%) mg/L	1.35 (1.2–1.52) highest vs lowest tertile	1 · pharmacologic
Alpha-Klotho	Aging & Senescence	860 → 755 (-12%) pg/mL	1.21 (1.01–1.45) highest vs lowest quartile	1 · pharmacologic
Angiopoietin-2	Coagulation	1.785 → 2.594 (+45%) ng/mL	1.46 (1.28–1.66) highest vs lowest tertile	—
Ankle-brachial index	Vascular	0.9476 → 1.123 (+18%) ratio	1.9 (1.3–2.8) highest vs lowest quartile	1 · pharmacologic
Antinuclear Antibodies (ANA)	Inflammation	0.1012 → 0.2398 (+137%) titre (positive/negative)	1.31 (1.16–1.48) highest vs lowest quartile	—
Apolipoprotein A1 (ApoA1)	Lipids & Apolipoproteins	140 → 148 (+6%) mg/dL	0.81 (0.74–0.88) per 1 SD	5 · exercise, diet, pharmacologic
Apolipoprotein B (ApoB)	Lipids & Apolipoproteins	81 → 94 (+16%) mg/dL	1.38 (1.27–1.5) per 1 SD	10 · pharmacologic, diet, clinical_procedure
Apolipoprotein B to A1 Ratio (ApoB/ApoA1)	Cardiometabolic	0.8096 → 0.9592 (+18%) ratio	1.08 (–) per 1 SD	2 · pharmacologic
Appendicular Lean Mass / Sarcopenia Index	Anthropometric	7.5 → 7.1 (-5%) kg/m2	0.5 (0.27–0.92) per 1 SD	2 · pharmacologic, supplement
Aspartate Aminotransferase (AST)	Liver & Nutritional	21 → 22 (+5%) U/L	1.39 (1.18–1.64) highest vs lowest quartile	8 · behavioral, diet, nutraceutical
Asymmetric Dimethylarginine (ADMA)	Cardiometabolic	0.4048 → 0.545 (+35%) umol/L	1.34 (1.19–1.51) highest vs lowest tertile	3 · exercise, pharmacologic
Basal Metabolic Rate	Anthropometric	1455 → 1578 (+8%) kcal/day	1.21 (1.08–1.36) highest vs lowest tertile	1 · diet
Basophil Count	Hematology	0.0405 → 0.0512 (+26%) 10^3 cells/uL	1.2 (1.07–1.34) highest vs lowest tertile	—
Beta-2 Microglobulin	Renal & Purine	1.25 → 1.5 (+20%) mg/L	2.5 (1.9–3.28) highest vs lowest quartile	1 · clinical
Beta-Trace Protein (BTP)	Renal & Purine	0.5336 → 0.7412 (+39%) mg/L	1.41 (1.24–1.6) highest vs lowest tertile	—
Blood Lead	Electrolytes & Minerals	0.8648 → 1.548 (+79%) ug/dL	1.55 (1.38–1.74) highest vs lowest quartile	—
Blood Urea Nitrogen (BUN)	Renal & Purine	11 → 16 (+45%) mg/dL	1.34 (1.28–1.4) per 1 SD	5 · diet, lifestyle, pharmacologic
Body Fat Percentage	Anthropometric	27.05 → 35.32 (+31%) %	1.38 (1.22–1.56) highest vs lowest quartile	5 · exercise, supplement, pharmacologic
Body Mass Index (BMI)	Anthropometric	26.5 → 29 (+9%) kg/m2	1.44 (1.4–1.49) highest vs lowest quartile	4 · diet, lifestyle, exercise
Body Weight	Anthropometric	75.99 → 86.33 (+14%) kg	1.28 (1.16–1.42) highest vs lowest quartile	5 · pharmacologic, diet, lifestyle
Bone Mineral Density T-score (DXA)	Bone & Mineral	0.5 → -1.5 (-400%) T-score	1.17 (1.13–1.22) per 1 SD	1 · pharmacologic
Broadband Ultrasound Attenuation (Heel)	Bone & Mineral	77.83 → 74.34 (-4%) dB/MHz	1.28 (1.14–1.44) highest vs lowest tertile	4 · pharmacologic, exercise
C-peptide	Vitamins & Endocrine	1.702 → 2.017 (+18%) ng/mL	1.8 (1.33–2.43) highest vs lowest quartile	2 · supplement, pharmacologic
C-Terminal Telopeptide of Type I Collagen (CTX)	Bone & Mineral	0.23 → 0.2725 (+18%) ng/mL	1.7 (1.4–2) highest vs lowest tertile	1 · pharmacologic
Calf Circumference	Anthropometric	33.58 → 39.78 (+18%) cm	0.86 (0.76–0.96) per 1 SD	1 · diet
Cardiac (Valvular/Annular) Calcification	Cardiac & Hemodynamics	2.3 → 2.725 (+18%) severity score	1.92 (1.28–2.87) highest vs lowest quartile	1 · pharmacologic
Carotid intima-media thickness	Vascular	0.6992 → 0.8284 (+18%) mm	1.54 (1.32–1.79) highest vs lowest tertile	2 · pharmacologic, diet
Carotid-Femoral Pulse Wave Velocity (PWV)	Cardiac & Hemodynamics	6.3 → 10.4 (+65%) m/s	1.35 (1.24–1.47) per 1 SD	4 · exercise, clinical, supplement
CD4:CD8 T-Cell Ratio	Inflammation	1.766 → 1.94 (+10%) ratio	1.32 (1.17–1.49) highest vs lowest tertile	1 · supplement
CD8+ T-Cell Count	Inflammation	0.5042 → 0.5188 (+3%) 10^3 cells/uL	1.26 (1.12–1.41) highest vs lowest tertile	—
Chronotropic Index	Functional Fitness	0.8096 → 0.8066 (-0%) ratio	1.39 (1.23–1.57) highest vs lowest tertile	—
Coagulation Factor VIIc	Coagulation	90.71 → 125.1 (+38%) IU/dL	1.34 (1.18–1.52) highest vs lowest tertile	5 · diet
Coagulation Factor VIII	Coagulation	103.4 → 155.4 (+50%) IU/dL	1.51 (1.34–1.7) highest vs lowest tertile	—
Copeptin	Cardiac & Hemodynamics	3.864 → 4.578 (+18%) pmol/L	1.7 (1.2–2.5) highest vs lowest quartile	3 · pharmacologic, exercise
Coronary artery calcium	Vascular	59.8 → 70.85 (+18%) Agatston units	2.67 (2.29–3.11) highest vs lowest quartile	3 · supplement, pharmacologic
Corrected QT Interval (QTc)	Cardiac & Hemodynamics	377.2 → 464.3 (+23%) ms	1.41 (1.26–1.58) highest vs lowest tertile	5 · pharmacologic, lifestyle
D-dimer	Coagulation	0.2302 → 0.2313 (+0%) ug/mL	1.97 (1.67–2.27) highest vs lowest tertile	1 · clinical
Daily Step Count	Functional Fitness	7949 → 6475 (-19%) steps/day	1.51 (1.32–1.73) highest vs lowest tertile	4 · diet, behavioral
De Ritis Ratio (AST/ALT)	Liver & Nutritional	0.9476 → 1.123 (+18%) ratio	1.58 (1.12–2.22) highest vs lowest quartile	1 · clinical
Dehydroepiandrosterone Sulfate (DHEA-S)	Vitamins & Endocrine	85.31 → 57.26 (-33%) ug/dL	1.51 (1.25–1.82) highest vs lowest quartile	2 · nutraceutical, supplement
Diastolic Blood Pressure (DBP)	Cardiac & Hemodynamics	—	1.22 (1.17–1.28) per 1 SD	8 · pharmacologic, exercise, behavioral
DNA Methylation Age Acceleration (PhenoAge/GrimAge)	Aging & Senescence	—	1.22 (1.08–1.25) per 1 SD	1 · sleep
Eosinophil Count	Hematology	0.26 → 0.3 (+15%) 1000 cells/uL	2.2 (1.84–2.62) highest vs lowest quartile	2 · pharmacologic
Erythrocyte Sedimentation Rate (ESR)	Inflammation	8 → 15 (+88%) mm/hr	1.54 (1.28–1.85) highest vs lowest quartile	7 · pharmacologic, diet, exercise
Estimated Glomerular Filtration Rate (eGFR)	Renal & Purine	110 → 76 (-31%) mL/min/1.73m2	1.57 (1.41–1.74) highest vs lowest tertile	8 · pharmacologic, clinical_procedure
Estradiol (17beta-Estradiol)	Endocrine	134.5 → 74.56 (-45%) pg/mL	1.29 (1.14–1.46) highest vs lowest tertile	—
Estradiol-to-SHBG Ratio	Vitamins & Endocrine	4.278 → 5.069 (+18%) ratio	1.82 (1.03–3.24) highest vs lowest quartile	2 · diet, lifestyle
Exercise Capacity (METs)	Functional Fitness	6.44 → 7.63 (+18%) METs	1.73 (1.35–2.22) per unit (1.0)	1 · lifestyle
Extracoronary Calcification Site Count	Cardiac & Hemodynamics	0.92 → 1.09 (+18%) site count	2.3 (1.6–3.31) highest vs lowest quartile	—
Fasting Plasma Glucose	Glycemic & Metabolic	95 → 106 (+12%) mg/dL	1.35 (1.25–1.45) per 1 SD	11 · pharmacologic, diet, exercise
Fasting Serum Insulin	Glycemic & Metabolic	9.1 → 10.1 (+11%) uIU/mL	1.33 (1.17–1.51) highest vs lowest quartile	7 · diet, exercise, pharmacologic
Fat Mass	Anthropometric	21.16 → 28.56 (+35%) kg	1.42 (1.28–1.58) highest vs lowest tertile	4 · pharmacologic, supplement, exercise
Fat-Free Mass	Anthropometric	50.23 → 53.85 (+7%) kg	1.34 (1.18–1.52) highest vs lowest tertile	4 · supplement, pharmacologic, diet
FEV1/FEV6 Ratio	Functional Fitness	0.7544 → 0.7957 (+5%) ratio	1.36 (1.2–1.54) highest vs lowest tertile	—
FIB-4 Index (NAFLD Fibrosis Score)	Liver & Nutritional	0.6 → 1.4 (+133%) index	1.64 (1.23–2.18) highest vs lowest quartile	1 · nutraceutical
Fibrinogen	Inflammation	312 → 376 (+21%) mg/dL	1.37 (1.28–1.46) per 1 SD	5 · exercise, behavioral, pharmacologic
Follicle-Stimulating Hormone (FSH)	Endocrine	8.464 → 61.26 (+624%) IU/L	1.23 (1.1–1.38) highest vs lowest tertile	4 · nutraceutical, pharmacologic
Forced Expiratory Volume in 1 Second (FEV1)	Functional Fitness	3.33 → 2.856 (-14%) L	1.49 (1.34–1.66) highest vs lowest tertile	3 · exercise, behavioral, clinical
Forced vital capacity	Cardiorespiratory	4.232 → 5.014 (+18%) L	2.21 (1.14–4.3) highest vs lowest quartile	5 · pharmacologic, clinical
Free Triiodothyronine (Free T3)	Vitamins & Endocrine	3.003 → 2.993 (-0%) pg/mL	0.81 (0.7–0.93) per 1 SD	1 · pharmacologic
Gait speed	Motor performance	1.35 → 0.95 (-30%) m/s	0.73 (–) per 1 SD	4 · exercise
Galectin-3	Cardiac & Hemodynamics	12.6 → 14.93 (+18%) ng/mL	1.1 (1.05–1.14) per 1 SD	—
Gamma-Glutamyl Transferase (GGT)	Liver & Nutritional	18 → 23 (+28%) U/L	1.45 (1.32–1.59) highest vs lowest tertile	8 · behavioral, diet, nutraceutical
Global longitudinal strain	Cardiac structure and function	-18.4 → -21.8 (+18%) %	1.45 (1.19–1.77) per 1 SD	3 · pharmacologic
Glycated Hemoglobin (HbA1c)	Glycemic & Metabolic	5.3 → 5.7 (+8%) %	1.52 (1.36–1.7) highest vs lowest quartile	11 · pharmacologic, lifestyle, diet
Growth Differentiation Factor-15 (GDF-15)	Inflammation	600 → 1300 (+117%) pg/mL	2.52 (2.06–2.97) highest vs lowest quartile	—
Growth Hormone (GH)	Endocrine	1.214 → 1.831 (+51%) ng/mL	1.22 (1.09–1.37) highest vs lowest tertile	2 · pharmacologic
HDL Cholesterol	Lipids & Apolipoproteins	50 → 52 (+4%) mg/dL	1.39 (1.25–1.54) highest vs lowest quartile	9 · exercise, behavioral, diet
Heart Rate Recovery (1 min)	Functional Fitness	24.66 → 20.06 (-19%) bpm	1.45 (1.28–1.64) highest vs lowest tertile	4 · exercise, clinical
Heart-Type Fatty Acid-Binding Protein (H-FABP)	Cardiac & Hemodynamics	3.33 → 6.366 (+91%) ng/mL	1.52 (1.32–1.74) highest vs lowest tertile	—
Hematocrit	Hematology	41.2 → 40.5 (-2%) %	—	5 · clinical, pharmacologic, environmental
Hemoglobin Concentration	Hematology	14.4 → 14 (-3%) g/dL	1.41 (1.25–1.59) highest vs lowest quartile	8 · pharmacologic, nutraceutical, exercise
High-Sensitivity C-Reactive Protein (hs-CRP)	Inflammation	1.3 → 2.2 (+69%) mg/L	1.42 (1.22–1.65) per 1 SD	11 · diet, pharmacologic, exercise
High-Sensitivity Cardiac Troponin I (hs-cTnI)	Cardiac & Hemodynamics	1.38 → 1.635 (+18%) ng/L	1.44 (1.18–1.77) per unit (1.0)	5 · pharmacologic, clinical
High-Sensitivity Cardiac Troponin T (hs-cTnT)	Cardiac & Hemodynamics	3 → 7.4 (+147%) ng/L	1.88 (1.66–2.12) highest vs lowest quartile	6 · pharmacologic, lifestyle, clinical_procedure
Hip Circumference	Anthropometric	97.34 → 115.5 (+19%) cm	1.22 (1.1–1.36) highest vs lowest tertile	4 · exercise, clinical, diet
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	Glycemic & Metabolic	2.12 → 2.52 (+19%) index	1.46 (1.24–1.72) highest vs lowest quartile	9 · pharmacologic, lifestyle, exercise
Homoarginine	Cardiometabolic	1.711 → 1.7 (-1%) umol/L	1.33 (1.18–1.5) highest vs lowest tertile	3 · supplement, pharmacologic
Homocysteine	Metabolic	7.09 → 9.79 (+38%) umol/L	1.58 (1.28–1.95) highest vs lowest quartile	3 · supplement, clinical
Immature Reticulocyte Fraction	Hematology	3.864 → 5.668 (+47%) %	1.29 (1.15–1.44) highest vs lowest tertile	—
Immunoglobulin A (IgA)	Inflammation	191.9 → 251.6 (+31%) mg/dL	1.23 (1.1–1.38) highest vs lowest tertile	—
Immunoglobulin G (IgG)	Inflammation	1038 → 1273 (+23%) mg/dL	1.24 (1.11–1.39) highest vs lowest tertile	1 · pharmacologic
Immunoglobulin M (IgM)	Inflammation	123.5 → 126.9 (+3%) mg/dL	1.22 (1.09–1.37) highest vs lowest tertile	—
Insulin-like Growth Factor 1 (IGF-1)	Vitamins & Endocrine	137.8 → 127 (-8%) ng/mL	1.33 (1.14–1.57) highest vs lowest tertile	1 · diet
Interleukin-1 beta (IL-1b)	Inflammation	0.46 → 0.545 (+18%) pg/mL	1.71 (1.01–2.9) highest vs lowest tertile	2 · nutraceutical, pharmacologic
Interleukin-10 (IL-10)	Inflammation	0.2327 → 0.2464 (+6%) pg/mL	1.84 (1.08–3.12) highest vs lowest tertile	—
Interleukin-18 (IL-18)	Inflammation	188.6 → 223.4 (+18%) pg/mL	1.19 (1.07–1.33) per 1 SD	—
Interleukin-6 (IL-6)	Inflammation	2.283 → 3.088 (+35%) pg/mL	1.42 (1.3–1.55) highest vs lowest tertile	5 · pharmacologic, exercise, nutraceutical
Interleukin-8 (IL-8)	Inflammation	12.26 → 13.24 (+8%) pg/mL	1.18 (1.06–1.3) per 1 SD	2 · supplement
Interventricular Septum Thickness	Cardiac & Hemodynamics	7.636 → 9.047 (+18%) mm	1.21 (1.05–1.39) per 1 SD	4 · clinical, pharmacologic
Kidney Injury Molecule-1 (KIM-1)	Renal & Purine	0.46 → 0.545 (+18%) ng/mL	1.17 (1.04–1.31) per 1 SD	1 · pharmacologic
LDL Cholesterol	Lipids & Apolipoproteins	102 → 111 (+9%) mg/dL	1.25 (1.15–1.36) highest vs lowest quartile	9 · pharmacologic, diet, clinical_procedure
Left Ventricular Diastolic Dysfunction Grade	Cardiac & Hemodynamics	0.368 → 0.436 (+18%) grade	4 (2.14–7.47) highest vs lowest quartile	—
Left-ventricular ejection fraction	Cardiac structure and function	57.78 → 68.45 (+18%) %	6 (2.9–12) highest vs lowest quartile	4 · pharmacologic
Leukocyte Telomere Length	Aging & Senescence	6.15 → 5.35 (-13%) kb	1.09 (1.06–1.13) per 1 SD	1 · supplement
Lipid Accumulation Product (LAP)	Cardiometabolic	50.6 → 59.95 (+18%) cm x mmol/L	4.28 (1.94–9.44) highest vs lowest tertile	—
Lipoprotein(a) [Lp(a)]	Lipids & Apolipoproteins	19.5 → 22.5 (+15%) nmol/L	1.22 (1.13–1.32) highest vs lowest tertile	11 · pharmacologic, clinical_procedure, physiological
Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)	Cardiometabolic	165.6 → 196.2 (+18%) nmol/min/mL	1.23 (1.02–1.5) highest vs lowest tertile	2 · pharmacologic
Lymphocyte Percentage	Hematology	29.99 → 30.3 (+1%) %	1.24 (1.12–1.37) highest vs lowest tertile	—
Lymphocyte-to-Monocyte Ratio (LMR)	Inflammation	5.5 → 3.5 (-36%) ratio	1.65 (1.35–2.02) highest vs lowest quartile	—
Mean Arterial Pressure	Cardiac & Hemodynamics	82.43 → 107.3 (+30%) mmHg	1.32 (1.2–1.46) highest vs lowest tertile	4 · exercise
Mean Corpuscular Volume (MCV)	Hematology	90.5 → 89.8 (-1%) fL	1.29 (–) per 1 SD	—
Mean Platelet Volume (MPV)	Hematology	9.8 → 9.2 (-6%) fL	1.42 (1.15–1.75) highest vs lowest quartile	—
Mean Reticulocyte Volume	Hematology	94.21 → 114.5 (+21%) fL	1.25 (1.12–1.4) highest vs lowest tertile	—
Mean Sphered Cell Volume	Hematology	87.22 → 105.5 (+21%) fL	1.21 (1.09–1.35) highest vs lowest tertile	—
Metabolic Syndrome (Harmonized Definition)	Cardiometabolic	0.184 → 0.5559 (+202%) present/absent	1.62 (1.44–1.82) highest vs lowest quartile	—
Mid-Regional Pro-Adrenomedullin (MR-proADM)	Cardiac & Hemodynamics	0.3496 → 0.4142 (+18%) nmol/L	2.37 (1.72–3.26) highest vs lowest quartile	1 · pharmacologic
Mid-Upper-Arm Circumference	Anthropometric	30.91 → 35.53 (+15%) cm	1.31 (1.16–1.48) highest vs lowest tertile	3 · pharmacologic, exercise, clinical
Mitochondrial DNA Copy Number	Aging & Senescence	257.6 → 305.2 (+18%) copies/cell	1.47 (1.33–1.62) highest vs lowest quartile	—
Monocyte Chemoattractant Protein-1 (MCP-1 / CCL2)	Inflammation	154.6 → 183.1 (+18%) pg/mL	2.11 (1.31–3.4) highest vs lowest tertile	—
Monocyte Count	Hematology	0.56 → 0.6 (+7%) 1000 cells/uL	1.31 (–) per 1 SD	—
Monocyte Percentage	Hematology	6.9 → 9.156 (+33%) %	1.23 (1.11–1.36) highest vs lowest tertile	—
Muscle strength	Musculoskeletal	41 → 31.5 (-23%) kg	0.74 (0.69–0.79) per 1 SD	7 · exercise, lifestyle, clinical_procedure
Myeloperoxidase (MPO)	Inflammation	92 → 109 (+18%) ug/L	1.97 (1.02–3.8) highest vs lowest tertile	1 · pharmacologic
N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP)	Cardiac & Hemodynamics	32 → 102 (+219%) pg/mL	1.76 (1.58–1.96) highest vs lowest tertile	9 · pharmacologic, lifestyle, clinical_procedure
Neopterin	Inflammation	4.563 → 5.406 (+18%) nmol/L	1.3 (1.1–1.55) highest vs lowest quartile	1 · clinical
Neurofilament Light Chain (NfL)	Neuro	5.5 → 14.5 (+164%) pg/mL	1.88 (1.6–2.2) per 1 SD	2 · pharmacologic, clinical
Neutrophil Gelatinase-Associated Lipocalin (NGAL)	Renal & Purine	95.68 → 113.4 (+18%) ng/mL	1.19 (1.07–1.32) per 1 SD	3 · clinical, pharmacologic
Neutrophil Percentage	Hematology	52.81 → 67.8 (+28%) %	1.26 (1.14–1.4) highest vs lowest tertile	—
Neutrophil-to-Lymphocyte Ratio (NLR)	Inflammation	1.74 → 2.08 (+20%) ratio	1.64 (1.45–1.85) highest vs lowest quartile	5 · exercise, behavioral, nutraceutical
Non-HDL Cholesterol	Cardiometabolic	116 → 136 (+17%) mg/dL	1.53 (1.35–1.74) highest vs lowest quartile	6 · pharmacologic, nutraceutical
Orthostatic Blood Pressure Drop	Autonomic	0.368 → 0.436 (+18%) mmHg	1.7 (1.4–2) highest vs lowest quartile	—
Osteocalcin	Bone & Mineral	14.72 → 17.44 (+18%) ng/mL	1.82 (1.41–2.35) highest vs lowest quartile	4 · pharmacologic, exercise
Osteoprotegerin (OPG)	Bone & Mineral	3.386 → 5.515 (+63%) pmol/L	1.37 (1.22–1.54) highest vs lowest tertile	—
Parathyroid Hormone (PTH)	Bone & Mineral	35.88 → 42.51 (+18%) pg/mL	1.19 (1.08–1.3) highest vs lowest quartile	1 · pharmacologic
Peak Expiratory Flow (PEF)	Functional Fitness	345 → 408.8 (+18%) L/min	2.49 (1.9–3.2) highest vs lowest quartile	4 · pharmacologic, exercise
Pentraxin-3 (PTX3)	Inflammation	1.638 → 1.94 (+18%) ng/mL	1.08 (1.02–1.15) per 1 SD	—
Pericardial Fat Volume	Cardiac & Hemodynamics	78.11 → 92.54 (+18%) cm3	1.34 (1.01–1.78) per 1 SD	1 · pharmacologic
Peroxiredoxin-4 (PRDX4)	Oxidative Stress	11.22 → 14.82 (+32%) ng/mL	1.29 (1.15–1.45) highest vs lowest tertile	—
Plasma Viscosity	Coagulation	1.141 → 1.406 (+23%) mPa.s	1.42 (1.26–1.6) highest vs lowest tertile	3 · supplement, pharmacologic, clinical
Plasminogen Activator Inhibitor-1 (PAI-1)	Coagulation	10.12 → 11.99 (+18%) ng/mL	—	4 · pharmacologic, diet
Platelet Count	Hematology	245 → 223 (-9%) 10^3 cells/uL	1.32 (1.18–1.47) highest vs lowest quartile	2 · pharmacologic
Platelet Distribution Width	Hematology	15 → 18.09 (+21%) fL	1.27 (1.14–1.42) highest vs lowest tertile	1 · pharmacologic
Plateletcrit (PCT)	Hematology	0.2116 → 0.2507 (+18%) %	1.5 (1.3–1.9) highest vs lowest quartile	—
PR Interval	Cardiac & Hemodynamics	143.5 → 180.9 (+26%) ms	1.22 (1.1–1.36) highest vs lowest tertile	2 · pharmacologic
Predicted Mass (UKB Impedance)	Anthropometric	68.26 → 78.48 (+15%) kg	1.24 (1.14–1.35) highest vs lowest tertile	—
Procalcitonin	Inflammation	0.02 → 0.04 (+100%) ng/mL	1.52 (1.07–2.16) highest vs lowest quartile	—
Proinsulin	Glycemic & Metabolic	3.68 → 4.36 (+18%) pmol/L	1.7 (1.1–2.4) highest vs lowest tertile	—
Prolactin	Endocrine	10.49 → 10.03 (-4%) ng/mL	1.24 (1.11–1.39) highest vs lowest tertile	4 · pharmacologic, supplement
Proteinuria (Dipstick)	Urine Biomarkers	0.046 → 0.1962 (+327%) ordinal (0-4)	1.68 (1.48–1.9) highest vs lowest quartile	—
Pulse Pressure	Cardiac & Hemodynamics	40.2 → 47.63 (+18%) mmHg	1.4 (1.34–1.46) per 1 SD	3 · nutraceutical, behavioral, pharmacologic
QRS Duration	Cardiac & Hemodynamics	82.98 → 104 (+25%) ms	1.38 (1.22–1.56) highest vs lowest tertile	2 · clinical
QRS-T Angle	Cardiac & Hemodynamics	36.98 → 54.94 (+49%) degrees	1.48 (1.3–1.68) highest vs lowest tertile	—
QT Interval	Cardiac & Hemodynamics	362.5 → 446.9 (+23%) ms	1.34 (1.2–1.5) highest vs lowest tertile	4 · pharmacologic, diet
Red Blood Cell Count	Hematology	4.471 → 5.101 (+14%) 10^6 cells/uL	1.28 (1.16–1.42) highest vs lowest tertile	—
Red Cell Distribution Width (RDW)	Hematology	12.6 → 13.3 (+6%) %	1.29 (1.21–1.38) per 1 SD	5 · nutraceutical, exercise, diet
Remnant Cholesterol	Lipids & Apolipoproteins	0.552 → 0.654 (+18%) mmol/L	1.6 (1.4–1.9) highest vs lowest quartile	3 · pharmacologic, supplement
Renal Artery Calcification	Renal & Purine	1.84 → 2.18 (+18%) severity score	1.63 (1.17–2.29) highest vs lowest quartile	—
Resting Heart Rate (RHR)	Cardiac & Hemodynamics	72 → 71 (-1%) bpm	1.27 (1.15–1.4) per 1 SD	1 · exercise
Reticulocyte Count (Absolute)	Hematology	0.0478 → 0.0621 (+30%) 10^6 cells/uL	1.24 (1.1–1.4) highest vs lowest tertile	1 · pharmacologic
Reticulocyte Percentage	Hematology	1.012 → 1.308 (+29%) %	1.22 (1.09–1.37) highest vs lowest tertile	3 · supplement, clinical
Rheumatoid Factor	Inflammation	7.912 → 18.75 (+137%) IU/mL	1.32 (1.18–1.48) highest vs lowest tertile	—
Serum 25-Hydroxyvitamin D	Vitamins & Endocrine	66.8 → 78.6 (+18%) nmol/L	0.74 (0.67–0.82) highest vs lowest tertile	9 · nutraceutical, environmental, diet
Serum Albumin	Liver & Nutritional	4.4 → 4.1 (-7%) g/dL	0.76 (0.69–0.83) per 1 SD	8 · diet, pharmacologic, clinical_procedure
Serum beta-Cryptoxanthin	Nutritional	7.728 → 9.81 (+27%) ug/dL	1.21 (1.08–1.36) highest vs lowest tertile	—
Serum Bicarbonate	Electrolytes & Minerals	23.18 → 27.47 (+18%) mEq/L	1.46 (1.07–2) highest vs lowest quartile	5 · clinical, pharmacologic, supplement
Serum Calcium	Electrolytes & Minerals	9.5 → 9.4 (-1%) mg/dL	1.34 (1.15–1.56) highest vs lowest quartile	5 · pharmacologic, clinical_procedure, nutraceutical
Serum Chloride	Electrolytes & Minerals	94.94 → 112.5 (+18%) mmol/L	1.3 (1.11–1.49) highest vs lowest quartile	4 · clinical, diet
Serum Citrate	Metabolic	0.0975 → 0.1308 (+34%) mmol/L	1.25 (1.12–1.4) highest vs lowest tertile	—
Serum Cortisol	Vitamins & Endocrine	14.2 → 12.8 (-10%) ug/dL	1.3 (1.09–1.55) per 1 SD	—
Serum Cotinine	Nutritional	0.05 → 0.04 (-20%) ng/mL	2.1 (1.82–2.42) highest vs lowest quartile	—
Serum Creatinine	Renal & Purine	0.87 → 0.93 (+7%) mg/dL	1.43 (1.31–1.56) per 1 SD	8 · pharmacologic, lifestyle, clinical_procedure
Serum Cystatin C	Renal & Purine	0.72 → 0.98 (+36%) mg/L	1.61 (1.48–1.76) per 1 SD	5 · pharmacologic, clinical_procedure, lifestyle
Serum Ferritin	Inflammation	72 → 122 (+69%) ug/L	1.4 (1.2–1.64) highest vs lowest tertile	7 · clinical_procedure, nutraceutical, diet
Serum Folate	Vitamins & Endocrine	18.5 → 16.5 (-11%) ng/mL	0.35 (–) per 1 SD	—
Serum Iron	Hematology	90.71 → 114.2 (+26%) ug/dL	1.27 (1.14–1.42) highest vs lowest tertile	—
Serum Leptin	Endocrine	9.752 → 14.82 (+52%) ng/mL	1.26 (1.13–1.41) highest vs lowest tertile	1 · diet
Serum Lutein + Zeaxanthin	Nutritional	16.38 → 21.15 (+29%) ug/dL	1.24 (1.11–1.39) highest vs lowest tertile	—
Serum Lycopene	Nutritional	37.9 → 48.61 (+28%) ug/dL	1.25 (1.12–1.4) highest vs lowest tertile	1 · diet
Serum Magnesium	Electrolytes & Minerals	0.7728 → 0.9156 (+18%) mmol/L	1.29 (1.16–1.44) highest vs lowest tertile	—
Serum Phosphate	Electrolytes & Minerals	3.65 → 3.62 (-1%) mg/dL	1.27 (1.11–1.45) highest vs lowest quartile	5 · pharmacologic, diet, clinical_procedure
Serum Potassium	Electrolytes & Minerals	4.1 → 4.2 (+2%) mmol/L	1.55 (1.35–1.78) highest vs lowest quartile	1 · pharmacologic
Serum Selenium	Electrolytes & Minerals	116 → 109 (-6%) ug/L	0.87 (0.83–0.9) per 1 SD	—
Serum Sodium	Electrolytes & Minerals	140 → 139 (-1%) mmol/L	1.48 (1.25–1.76) highest vs lowest quartile	—
Serum Total Bilirubin	Liver & Nutritional	0.58 → 0.62 (+7%) mg/dL	0.84 (0.77–0.91) per 1 SD	5 · physiological, clinical_procedure, lifestyle
Serum trans-Lycopene	Nutritional	19.87 → 25.72 (+29%) ug/dL	1.23 (1.1–1.38) highest vs lowest tertile	2 · diet
Serum Triglycerides	Lipids & Apolipoproteins	97 → 119 (+23%) mg/dL	1.18 (1.11–1.26) per 1 SD	10 · pharmacologic, diet, exercise
Serum Uric Acid	Renal & Purine	5 → 5.5 (+10%) mg/dL	1.24 (1.1–1.4) per 1 SD	8 · pharmacologic, diet, nutraceutical
Serum Vitamin A (Retinol)	Nutritional	1.748 → 2.202 (+26%) umol/L	1.26 (1.13–1.41) highest vs lowest tertile	—
Serum Vitamin C (Ascorbic Acid)	Nutritional	48.21 → 54.28 (+13%) umol/L	1.31 (1.16–1.48) highest vs lowest tertile	—
Serum Zinc	Electrolytes & Minerals	90 → 82 (-9%) ug/dL	1.94 (1.03–3.65) highest vs lowest quartile	—
Side-Step Test Score	Functional Fitness	39.19 → 36.84 (-6%) steps/20s	1.28 (1.14–1.44) highest vs lowest tertile	—
Sit-Up Count (Timed)	Functional Fitness	28.7 → 19.4 (-32%) repetitions	1.33 (1.18–1.5) highest vs lowest tertile	—
Sitting Height (Rump-to-Crown)	Anthropometric	85.19 → 95.27 (+12%) cm	1.24 (1.1–1.4) highest vs lowest tertile	—
Skeletal Muscle Fat Infiltration	Anthropometric	27.6 → 32.7 (+18%) index	1.18 (1.06–1.33) per 1 SD	—
Skinfold Thickness	Anthropometric	14.72 → 17.44 (+18%) mm	1.08 (1.02–1.15) per 1 SD	1 · lifestyle
Soluble CD14 (sCD14)	Inflammation	1481 → 1610 (+9%) ng/mL	1.27 (1.11–1.45) highest vs lowest quartile	1 · pharmacologic
Soluble CD163 (sCD163)	Inflammation	1748 → 2071 (+18%) ng/mL	1.35 (1.13–1.63) highest vs lowest quartile	—
Soluble ICAM-1 (sICAM-1)	Coagulation	213.6 → 215.1 (+1%) ng/mL	1.33 (1.18–1.5) highest vs lowest tertile	—
Soluble Tumor Necrosis Factor Receptor 1 (sTNFR1)	Inflammation	1141 → 1352 (+18%) pg/mL	1.3 (1.05–1.61) highest vs lowest quartile	—
Soluble Urokinase Plasminogen Activator Receptor (suPAR)	Inflammation	—	1.45 (1.05–2) highest vs lowest quartile	—
ST2 Soluble (sST2)	Cardiac & Hemodynamics	17.94 → 21.25 (+18%) ng/mL	2.1 (1.4–3.2) highest vs lowest quartile	1 · pharmacologic
Standing Height	Anthropometric	155.5 → 184.2 (+18%) cm	2.2 (1.1–4.3) highest vs lowest quartile	3 · pharmacologic
Stromal Cell-Derived Factor-1 (SDF-1/CXCL12)	Inflammation	1.987 → 2.551 (+28%) ng/mL	1.28 (1.14–1.44) highest vs lowest tertile	—
Symmetric Dimethylarginine (SDMA)	Renal & Purine	0.3496 → 0.4142 (+18%) umol/L	1.2 (1.07–1.25) per 1 SD	2 · pharmacologic
Systolic Blood Pressure (SBP)	Cardiac & Hemodynamics	115 → 132 (+15%) mmHg	1.26 (1.21–1.31) per 1 SD	9 · pharmacologic, diet, exercise
Testosterone-to-SHBG Ratio	Vitamins & Endocrine	0.552 → 0.654 (+18%) ratio	1.39 (1.14–1.7) highest vs lowest quartile	—
Thoracic Aorta Calcification (TAC)	Cardiac & Hemodynamics	1.84 → 2.18 (+18%) severity score	1.61 (1.1–2.27) highest vs lowest quartile	—
Thyroid-Stimulating Hormone (TSH)	Vitamins & Endocrine	1.9 → 2.3 (+21%) mIU/L	1.45 (1.12–1.87) highest vs lowest quartile	1 · pharmacologic
Thyroxine (Total T4)	Endocrine	7.636 → 8.676 (+14%) ug/dL	1.27 (1.14–1.42) highest vs lowest tertile	—
Total Body Water Mass	Anthropometric	36.98 → 39.68 (+7%) kg	1.22 (1.08–1.38) highest vs lowest tertile	2 · pharmacologic
Total Cholesterol	Lipids & Apolipoproteins	178 → 189 (+6%) mg/dL	1.28 (1.12–1.46) highest vs lowest quartile	8 · pharmacologic, diet, nutraceutical
Total Plasma Thiols	Oxidative Stress	425 → 503.6 (+18%) umol/L	0.73 (0.57–0.93) per unit (1.0)	2 · lifestyle, exercise
Total Protein	Liver & Nutritional	7.3 → 7.1 (-3%) g/dL	1.75 (1.04–2.96) highest vs lowest quartile	—
Total T-Cell Count	Inflammation	1.454 → 1.504 (+3%) 10^3 cells/uL	1.27 (1.13–1.42) highest vs lowest tertile	—
Total Testosterone	Vitamins & Endocrine	440 → 280 (-36%) ng/dL	0.89 (0.83–0.97) highest vs lowest quartile	2 · nutraceutical, diet
Transferrin Saturation	Hematology	—	1.6 (1.17–2.21) highest vs lowest quartile	2 · pharmacologic
Trefoil Factor 3 (TFF3)	Inflammation	2.41 → 3.423 (+42%) ng/mL	1.27 (1.13–1.42) highest vs lowest tertile	—
Trimethylamine N-oxide (TMAO)	Cardiometabolic	3.404 → 4.033 (+18%) umol/L	1.47 (1.25–1.69) highest vs lowest quartile	1 · supplement
Tumor Necrosis Factor-alpha (TNF-alpha)	Inflammation	2.057 → 2.21 (+7%) pg/mL	1.35 (1.16–1.58) highest vs lowest tertile	5 · pharmacologic, diet, nutraceutical
Urinary Creatinine Concentration	Urine Biomarkers	143 → 89 (-38%) mg/dL	0.78 (0.68–0.89) per 1 SD	5 · exercise, nutraceutical, diet
Urinary Flow Rate	Urine Biomarkers	1.1 → 0.98 (-11%) mL/min	1.37 (1.14–1.64) highest vs lowest quartile	3 · diet, clinical_procedure
Urine Albumin-to-Creatinine Ratio (uACR)	Urine Biomarkers	6.7 → 11.8 (+76%) mg/g	1.57 (1.44–1.72) per 1 SD	7 · pharmacologic, clinical_procedure
Urine Specific Gravity	Urine Biomarkers	1.02 → 1.016 (-0%) unitless	1.29 (1.11–1.5) highest vs lowest quartile	3 · pharmacologic, lifestyle
Vagal tone	Autonomic	157 → 112 (-29%) ms (24-h SDNN)	1.38 (1.13–1.7) per 1 SD	—
Vertical Jump Height	Functional Fitness	36.8 → 43.6 (+18%) cm	2.37 (1.8–3.1) highest vs lowest quartile	5 · exercise, supplement
Visceral fat	Body composition and tissue	1.086 → 1.788 (+65%) kg	1.46 (1.28–1.66) highest vs lowest tertile	4 · exercise, diet, pharmacologic
Vitamin B12 (Cobalamin)	Vitamins & Endocrine	395 → 345 (-13%) pg/mL	1.3 (1.03–1.64) highest vs lowest tertile	2 · supplement
Vitamin E (Alpha-Tocopherol)	Vitamins & Endocrine	23 → 27.25 (+18%) umol/L	1.28 (1.19–1.35) highest vs lowest quartile	1 · supplement
von Willebrand Factor (vWF)	Coagulation	99.36 → 117.7 (+18%) %	1.29 (0.98–1.7) highest vs lowest quartile	—
Waist Circumference	Anthropometric	86.3 → 111.6 (+29%) cm	1.44 (1.32–1.57) highest vs lowest quartile	5 · pharmacologic, diet, clinical
Waist-to-Height Ratio (WHtR)	Anthropometric	0.5109 → 0.5085 (-0%) ratio	1.19 (1.12–1.36) per 1 SD	1 · pharmacologic
Waist-to-Hip Ratio	Anthropometric	0.7912 → 1.003 (+27%) ratio	1.52 (1.38–1.68) highest vs lowest quartile	1 · pharmacologic
Waist-to-Thigh Ratio	Anthropometric	1.803 → 2.267 (+26%) ratio	1.26 (1.12–1.42) highest vs lowest tertile	—
White Blood Cell Count (WBC)	Hematology	6.9 → 7 (+1%) 10^3 cells/uL	1.44 (1.22–1.7) highest vs lowest quartile	—
YKL-40 (CHI3L1)	Inflammation	28 → 70 (+150%) ng/mL	1.9 (1.6–2.3) highest vs lowest quartile	1 · pharmacologic

How to read it

Change with age is a rate (per year or per decade) or a difference between age groups. The healthspan link is a hazard or odds ratio, or a correlation, with the outcome named. Remedies are randomised trials or meta-analyses; the magnitude is the change in the measure, in its own units, a percentage or a standardised mean difference, with the duration where the abstract gave it. Arrows show the direction of the measure, not whether that is good: a falling hearing threshold is an improvement. Rows tagged catalogue are values already stored in the landscape; the rest come directly from PubMed abstracts.