Exercise as a Modulator of Biological Age: The Role of Epigenetic Clocks in Assessing Exercise-Induced Rejuvenation – A Narrative Review
Abstract
Background: Biological age is increasingly recognized as a valuable indicator of the aging process. Compared with chronological age, it may provide a more accurate representation of an individual’s health status and disease risk. DNA methylation–based epigenetic clocks are among the most widely used biomarkers of biological aging. Aim: This narrative review aimed to summarize the current evidence on the association between physical activity and epigenetic aging and to evaluate the potential role of exercise as a modulator of biological age. Materials and methods: PubMed and Embase databases were searched from their inception through July 2026 using a combination of relevant keywords. A total of 79 studies were included in the review. Results: Current evidence indicates that higher levels of physical activity and physical fitness are generally associated with a lower rate of epigenetic aging and more favorable biological aging profiles. Aerobic exercise is the most extensively studied modality and demonstrates the most consistent associations with slower biological aging. Resistance training, high-intensity interval training, and multicomponent exercise programs may also exert beneficial effects through mechanisms involving mitochondrial function, regulation of inflammation, metabolic adaptation, and epigenetic remodeling. However, the findings remain heterogeneous due to differences in study populations, exercise protocols, follow-up durations, and the epigenetic clocks employed. Conclusions: Physical activity appears to be a promising, modifiable factor influencing biological aging. Accumulating evidence suggests that regular exercise may contribute to slower epigenetic aging and enhanced physiological resilience. Nevertheless, the magnitude and clinical significance of exercise-induced changes in epigenetic age remain incompletely understood. Further research is warranted.