Association of Accelerometer-Measured Physical Activity and Sedentary Time with Epigenetic Markers of Aging

We used linear regression to examine cross-sectional associations of accelerometer-measured physical activity and sedentary time with extrinsic and intrinsic epigenetic age acceleration models (EEAA and IEAA) and GrimAge measured from blood samples from Framingham Heart Study participants with accelerometry and DNA methylation data (n = 2435; mean age 54.9 ± 14.3, 46.0% men). Residuals of Hannum-, Horvath-, and GrimAge-predicted epigenetic age were calculated by regressing epigenetic age on chronological age. We took into account blood cell composition for EEAA, IEAA, and AdjGrimAge. Moderate to vigorous physical activity (MVPA) was log-transformed to normalize its distribution. Adjustment models accounted for family structure, age, sex, smoking status, cohort-laboratory indicator, and accelerometer wear time. We additionally explored adjustment for body mass index (BMI).Walking 1500 more steps/day or spending 3 fewer hours sedentary was associated with10 months lower GrimAge biological age (or ~ 1 month lower AdjGrimAge, after adjusting for blood cells, p0.05). Every 5 min/day more MVPA was associated with 19-79 days lower GrimAge (4-23 days lower using EEAA or AdjGrimAge, p0.01). Adjusting for BMI attenuated these results, but all statistically significant associations with AdjGrimAge remained.Greater habitual physical activity and lower sedentary time were associated with lower epigenetic age, which was partially explained by BMI. Further research should explore whether changes in physical activity influence methylation status and whether those modifications influence chronic disease risk.