Physical Activity Is Associated With Decreased Epigenetic Aging: Findings From the Health and Retirement Study.
Level 3 - non-randomized controlled study
Prospective cohort study analyzing longitudinal physical activity and cross-sectional epigenetic markers.
PubMed 40511567 · doi:10.1002/jcsm.13873
What was done
Participants in the Health and Retirement Study were followed biennially across 12 years (2004–2016). Moderate-to-vigorous physical activity was assessed by self-report at each wave; participants reporting vigorous activity at least once per week or moderate activity more than once per week were classified as physically active. In 2016, leukocyte DNA methylation was measured from venous blood samples to assess epigenetic age acceleration (EAA) using second-generation clocks (GrimAge, PhenoAge, and DunedinPACE). Analysis used weighted linear regression models adjusted for sociodemographic, lifestyle, and health factors, along with a structured life-course modelling approach (SLCMA) to evaluate timing and cumulative physical activity.
What was found
In 2016, 58% of participants were classified as physically active. In cross-sectional analysis, physically active individuals showed significantly lower EAA compared to inactive individuals: -1.26 years (95% CI: -1.59 to -0.93) for GrimAge acceleration, -1.70 years (95% CI: -2.26 to -1.15) for PhenoAge acceleration, and -0.05 years per chronological year (95% CI: -0.06 to -0.04) for DunedinPACE. Associations attenuated slightly but remained significant after further adjustment for body mass index, mobility limitations, and chronic disease diagnoses. Significant interactions indicated stronger associations in males than females for DunedinPACE (P = 0.04) and a positive association between physical activity and GrimAge EAA in Hispanic versus non-Hispanic White participants (P = 0.009). Longitudinal SLCMA identified both cumulative activity and concurrent 2016 activity as the strongest predictors of lower EAA.
Why it matters
This study provides evidence from a large aging cohort linking sustained long-term physical activity to slower biological aging across multiple validated DNA methylation clocks.
Limits
The total sample size is not stated in the abstract. Physical activity was self-reported rather than objectively measured, which risks recall and misclassification bias. DNA methylation was measured at only a single timepoint (2016), preventing evaluation of changes in epigenetic clocks over time.
Cited by
- supports Physical exercise tends to decrease epigenetic age.