Exercise and/or Stress Effects on the Epigenetic Clock

Abstract

Abstract Epigenetic alterations, including DNA methylation changes, are one of the primary hallmarks of aging and underlie many age-related diseases. Machine learning tools have prompted the development of epigenetic clocks, that is, extremely accurate age estimators that can predict a sample s age solely based on its DNA methylation profile. These epigenetic clocks and more specialized biological clocks that include disease biomarkers are used as tools to monitor aging and to gauge the efficacy of interventions promoting healthy aging. While regular exercise training is known to promote healthy aging, a handful of large-scale observational studies have reported weak or null associations between physical activity/fitness and epigenetic clocks in blood. However, these studies have also found stronger and clearer associations between physical activity/fitness and biological clocks in blood. Specifically, higher levels of physical activity and/or fitness were associated with lower biological age. While these studies were of relatively large scale, they suffered from a lack of refinement of the physical activity/fitness phenotype and from their cross-sectional setting prone to residual confounding. We suggest that future studies collect longitudinal, high-quality data on physical activity or fitness in multiple tissues to broaden our understanding of the effects of physical activity on epigenetic and biological clocks.