Kresovich · American journal of epidemiology 2021 · cross-sectional observational study · n=2,758

Associations of Body Composition and Physical Activity Level With Multiple Measures of Epigenetic Age Acceleration.

Cited 114 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional analysis of baseline cohort data

PubMed 33693587 · doi:10.1093/aje/kwaa251 · record verified 2026-08-31

What was done

Analyzed baseline blood samples and data collected at enrollment (2003-2009) from 2,758 women in the US nationwide Sister Study. Six epigenetic age acceleration metrics were derived using 4 epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge). Adiposity measures (BMI, waist-to-hip ratio, waist circumference) were measured by trained examiners, and recreational physical activity was self-reported.

What was found

All adiposity measures were associated with epigenetic age acceleration, with the strongest association between BMI and PhenoAge (BMI ≥35.0 vs. 18.5-24.9, β = 3.15 years, 95% CI: 2.41, 3.90; P for trend < 0.001). In mutually adjusted models, PhenoAge acceleration remained associated with BMI ≥35.0 (β = 2.69 years, 95% CI: 1.90, 3.48; P for trend < 0.001) and quartile 4 vs. 1 waist-to-hip ratio (β = 1.00 years, 95% CI: 0.34, 1.65; P for trend < 0.008). After adjustment, physical activity was associated only with GrimAge (quartile 4 vs. 1, β = -0.42 years, 95% CI: -0.70, -0.14; P for trend = 0.001) and attenuated the associations of waist circumference with PhenoAge and GrimAge.

Why it matters

This study provides evidence that excess adiposity is linked to accelerated biological aging across multiple epigenetic clocks, while physical activity may modestly offset some epigenetic age acceleration linked to central adiposity.

Limits

The study is cross-sectional, preventing causal inference or longitudinal assessment. Physical activity was self-reported, adiposity was measured only at baseline, and the cohort consisted exclusively of women in the Sister Study, limiting generalizability to men and broader populations.

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