Epigenetic clocks are typically created from bulk epigenetic data from immune cells in blood samples taken from a population of various ages. Machine learning techniques derive algorithmic combinations of DNA methylation status at hundreds or thousands of CpG sites on the genome that tightly correlate with chronological age or mortality risk. There are certainly other ways to go about the task, but this describes most of the earlier and more mainstream clocks. Interestingly, this approach produces clocks that do not appear to be all that sensitive to physical fitness, despite what we know about the correlations between physical fitness and life expectancy. This probably says something interesting about our biochemistry, but we do not know yet know what that interesting thing is.
Physical activity reduces the risk of mortality and age-related chronic diseases, yet its association with biological age measured by DNA methylation (DNAm) clocks remains unclear. This systematic review and meta-analysis aims to evaluate the association between physical activity and biological age measured by DNAm clocks.
We identified 44 studies that were included in a systematic review comprising 145,465 participants with mean ages ranging from 24.1 years to 78.5 years. Across studies, higher levels of physical activity were generally associated with lower DNAm age, although many individual associations did not reach statistical significance. Seven cross-sectional studies contributed to the meta-analysis. Each one standard deviation (SD) higher in metabolic equivalent of tasks (MET)-minutes per week was associated with 0.03 SD lower Horvath epigenetic age acceleration (EAA) and 0.09 SD lower GrimAge EAA. No statistically significant association was observed for Hannum EAA or PhenoAge EAA.
Higher physical activity is significantly associated with lower biological age as measured by Horvath EAA and GrimAge EAA. However, evidence is predominantly from cross-sectional studies, limiting causal inference. Future longitudinal studies and clinical trials using standardised, objectively measured physical activity are warranted to clarify dose-response relationships, and to determine whether physical activity can causally modify ageing trajectories, thereby informing precision strategies for healthy longevity.
Link: https://doi.org/10.1016/j.lanhl.2026.100835
View the full article at FightAging
