Alterations of the epigenetic landscape are a hallmark of aging, leading to aberrant gene expression profiles. Moreover, physical activity induces widespread changes in the methylome and miRNA expression profiles of various tissues, especially skeletal muscle. We hypothesized that 1) higher levels of physical activity are negatively associated with age-related epigenetic drift and 2) a 4-week high-intensity interval training program can reverse age-induced epigenetic drift.
To test our hypotheses, we generated genome-wide DNA methylation and miRNA expression profiles in skeletal muscle from 25 individuals who participated in the Gene Skeletal Muscle Adaptive Response to Training (SMART) study [1]. Participants were all healthy, recreationally active, Caucasian men aged 18-45. Muscle biopsies were taken from the vastus lateralis muscle at baseline and at the end of the 4 weeks of training. DNA methylation was assessed with the Illumina EPIC chip and miRNA expression profiles were generated with the TaqMan® Array Human MicroRNA A+B Cards Set v3.0. All preprocessing and downstream data analyses were performed in R with the limma package.
We found a strong inverse relationship between age-related and fitness-related epigenetic changes at baseline for both DNA methylation (r = -0.40, p < 0.001) and miRNA expression (r = -0.58, p < 0.001). We also found a strong inverse relationship between age-related methylome changes and methylome changes induced by four weeks of high-intensity interval training (r = -0.21, p<0.001), but this was not the case for miRNA expression (r = 0.070, p=0.35).
In summary, we found that fitter subjects displayed younger epigenetic profiles in skeletal muscle at baseline and an exercise intervention was able to shift DNA methylation profiles to younger profiles, but this was not the case for miRNA expression. This is the first direct evidence that physical activity can offset the effects of aging at the epigenetic level in skeletal muscle.