Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning.
Level 4 - case-series / case-control
Cross-sectional observational study across two cohorts including monozygotic twins
PubMed 34001218 · doi:10.1186/s13148-021-01094-6
What was done
Genome-wide DNA methylation was assessed in whole blood and skeletal muscle (m. vastus lateralis) across two independent cohorts of adults aged 23–69 years (Cohort 1: n = 139; Cohort 2: n = 47), including monozygotic twins. Four standard DNA methylation age estimates (including Horvath and GrimAge) and a muscle-specific clock algorithm (MEAT) were computed. Biological age acceleration estimates were compared against physical activity (questionnaires and accelerometers), cardiorespiratory fitness, muscle strength tests, and body composition via dual-energy X-ray absorptiometry.
What was found
Blood and muscle DNA methylation age estimates correlated strongly with chronological age, but different age acceleration estimates correlated weakly with each other. Monozygotic twin within-pair similarity of aging pace was higher in blood (r = 0.617 to 0.824) than in muscle (r = 0.523 to 0.585). Associations between age acceleration estimates and physical activity, physical function, or body composition were weak in both tissues and mostly explained by smoking and sex. Horvath's clock and GrimAge weakly linked higher physical activity to accelerated biological aging in muscle, which the authors interpreted as an artifact of epigenetic clock algorithms rather than true physiological age acceleration.
Why it matters
Existing blood and muscle epigenetic clocks reflect chronological age but provide little insight into functional muscle aging, fitness, or exercise adaptations.
Limits
The cross-sectional design precludes causal inference or longitudinal tracking. The total sample size was modest (n = 186 across two cohorts), and clocks trained strictly on chronological age may fundamentally lack sensitivity to functional or phenotypic muscular aging.
Cited by
- supports Physical activity measured by step counts has an inverse correlation of approximately -0.1 with epigenetic clocks such as GrimAge.