DNA Methylation Dynamics of Dose-dependent Acute Exercise, Training Adaptation, and Detraining

In this study, we focus on two combined endurance and resistance training programs: (1) traditional moderate-intensity continuous endurance and resistance exercise (TRAD) and (2) a variation of high-intensity interval training (HIIT) we refer to as high intensity tactical training (HITT), to assess the dynamics of DNA methylation (DNAm) in blood and muscle derived from males (N=23) and females (N=31), over a 12-week period of training followed by a 4-week period of detraining, sampled at pre-exercise and acute time points, totaling 528 samples. Due to its rapid responsiveness to stimuli and its stability, DNAm has been known to facilitate regulatory cascades that significantly affect various physiological processes and pathways. We find that several thousand differentially methylated regions (DMRs) associated with acute exercise in blood, many of which are shared across males and females. This trend is reversed when comparing the baseline (pre-exercise) time points at the untrained state with those at the post-conditioned state or acute time points post-training. Here, muscle shows most DNAm changes, with most of those being unique. We also find several hundred “memory” DMRs in muscle that maintain the gain or loss of methylation after four weeks of inactivity.