Physical Fitness is Associated with Slower Epigenetic Aging in U.S. Adults: Evidence from the National Health and Nutrition Examination Survey

Regular engagement in physical activity is a vital component of healthy aging and epigenetic clocks are powerful biomarkers of biological aging. However, the extent to which physical activity and fitness influences epigenetic aging in diverse populations remains unclear. We harnessed 2,346 participants (50-84 years of age) from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles. We examined associations of self-reported physical activity (moderate, vigorous, and muscle-strengthening), metabolic equivalent time, walking speed, and knee extensor strength with epigenetic age acceleration (EAA) measures from six epigenetic clocks using adjusted survey-weighted generalized linear regression. A 40 Newton-meter increase in peak knee extension torque was associated with lower EAA for PhenoAge (-1.09 years, 95% CI: -1.74, -0.44), GrimAge2 (-0.72 years, 95%CI: -1.14, -0.30), and DunedinPoAm (-0.015, 95% CI: -0.023, -0.007) in fully-adjusted models. Lower time to complete a 20-foot walk and self-reported physical activity were also associated with lower EAA across several clocks, although these associations attenuated after adjusting for smoking, self-reported health, height, and waist circumference. Greater knee extensor strength is associated with reduced epigenetic aging across several next-generation clocks in the general US population, while associations related to self-reported physical activity tended to attenuate after adjusting for health and behavioral factors.