Exercise as a geroprotector: focusing on epigenetic aging

Emerging evidence suggests that physical activity, exercise, and physical fitness may delay or reverse epigenetic aging, with implications for the extension of healthspan. This Perspective review defines essential exercise-related terminology and synthesizes findings from both human and animal studies examining the relationships between these factors and DNA methylation-based epigenetic clocks. While observational studies have demonstrated inverse relationships between cardiorespiratory fitness and epigenetic age acceleration, interventional studies further suggest that structured exercise training can induce epigenomic rejuvenation, particularly in blood and skeletal muscle. However, these effects exhibit considerable interindividual and organ-specific variability, underscoring the need for future research to elucidate causal mechanisms and organ-specific responses in order to optimize the application of exercise as a geroprotective intervention.