McGreevy · Aging 2023 · Observational cohort study (biomarker derivation and validation) · n=?

DNAmFitAge: biological age indicator incorporating physical fitness.

Cited 101 times in the scientific literature.

Level 3 - non-randomized controlled study

Observational biomarker development and cross-cohort validation study

PubMed 36812475 · doi:10.18632/aging.204538 · record verified 2026-08-30

What was done

Researchers developed blood-based DNA methylation (DNAm) surrogate biomarkers for four physical fitness parameters: gait speed, maximum handgrip strength, forced expiratory volume in one second (FEV1), and maximal oxygen uptake (VO2max). These DNAm measures were evaluated in five validation datasets. The fitness biomarkers were combined with the mortality-associated clock DNAmGrimAge to create DNAmFitAge, a composite biological age indicator. The authors tested DNAmFitAge against physical activity levels, bodybuilder cohorts versus controls, mortality, and morbidity outcomes.

What was found

The DNAm fitness biomarkers showed modest correlations with actual fitness measurements across five validation cohorts, with average r ranging between 0.16 and 0.48. DNAmFitAge was associated with physical activity levels across datasets (p = 6.4E-13). Male bodybuilders displayed significantly lower DNAmFitAge (p = 0.046) and higher DNAmVO2max (p = 0.023) compared to controls. A younger DNAmFitAge was statistically associated with lower mortality risk (p = 7.2E-51), reduced coronary heart disease risk (p = 2.6E-8), and higher likelihood of disease-free status (p = 1.1E-7).

Why it matters

This establishes an epigenetic aging metric that explicitly incorporates biological signatures of physical fitness and physical function, enabling fitness-related biological age estimation directly from blood samples.

Limits

The abstract does not state the total participant sample size across the five cohorts. The correlation between DNA methylation surrogates and true physical fitness metrics is modest (r = 0.16 to 0.48), indicating substantial unexplained variance. Observational validation cannot determine whether improving fitness directly reverses the epigenetic signature.

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