Genetics
Investigating the association between physical activity and epigenetic aging using structured life course modelling in the Health and Retirement Study Farah Ammous* Farah Ammous Jessica Faul Colter Mitchell
Regular physical activity is an effective lifestyle intervention for promoting wellbeing and healthy aging. One pathway by which exercise can shape biological processes is through epigenetic modifications. Investigating how and when exercise influences epigenetic processes offers promising avenues for tailored interventions. Using data from a representative sample of participants aged 56 years and older from the Health and Retirement Study, we investigated the association between physical exercise (Biennial follow-up from 2004–2016 for a total of seven waves) and epigenetic aging (2016). We defined exercise as moderate (≥ 2 per week) or vigorous intensity (≥ 1 per week) and used three epigenetic aging measures (GrimAA, PhenoAA, and pace of aging (PACE)). We applied weighted linear regression for cross-sectional associations in 2016 (N=3542) and a modified structured life-course modelling approach (SLCMA), testing three life-course hypotheses: accumulation, recency, and sensitive periods (N=2483). In 2016, participants who engaged in exercise were younger (69 vs. 71 years) and had a healthier cardiometabolic risk profile. After adjusting for age, sex, race/ethnicity, education, body mass index, diabetes, heart disease, stroke, total cholesterol, high density lipoprotein, and blood pressure, exercise was associated with decreased epigenetic aging (Beta = -1.0 years (95%CI: -0.7– -1.4) for GrimAA, -1.4 years (95%CI: -0.8 – -2.0) for PhenoAA and -0.03 (95%CI: -0.02 – -0.04) for PACE). For the three measures, SLCMA models selected the recency hypothesis, which considers an exposure cumulatively but inversely weighted by the length of time passed since it occurred. Our study shows that exercise is associated with slower epigenetic aging after adjusting for socioeconomic and cardiometabolic measures. Over a 12-year follow-up, reported exercise closest to the time of epigenetic aging assessment appears to have a stronger effect on aging compared to earlier exercise.