Exercise training modifies the whole blood DNA methylation profile in middle-aged and older women.

This is a longitudinal single-arm clinical trial aimed to investigate whether exercise training would modify the whole blood methylation profile in healthy women. A total of 45 subjects were engaged in an exercise training protocol during a 14-wk follow up, consisting of aerobic cardiorespiratory and muscle strength exercises. Subjects were evaluated at baseline (PRE), after 7 wk of exercise training (POST 7), and after 14 wk of exercise training (POST 14). Functional primary outcomes included anthropometric, blood pressure, biochemical measurements, physical tests, and global health assessments. Blood samples were collected at each time point to determine the methylation profile using a DNA methylation array technique screening up to 850k different sites. Exercise training decreased blood pressure and triglyceride levels and enhanced physical performance, including upper- and lower-body maximum strength. Moreover, exercise training improved markers of quality of life. In the array analysis, 14 wk of exercise training changed the methylation of more than 800 sites. Across these differentially methylated sites, we found that differentially methylated sites in the promoter region were more hypermethylated after exercise training, suggesting that this hypermethylation process may affect the transcription process. When inputting the differentially methylated sites in pathway analysis, we found several metabolic pathways, including AMPK signaling, TGF-β signaling, and insulin signaling. This study demonstrates that exercise training promotes a robust change in the whole blood methylation profile and provides new insights into the key regulators of exercise-induced benefits. We have shown that exercise training lowers blood pressure and triglyceride levels, improves physical performance, and improves quality of life in middle-aged and elderly women. Regarding epigenetic data, we noticed that more than 800 sites are differentially methylated in whole blood after physical training. We emphasize that the differentially methylated sites in the promoter region are more hypermethylated after physical training. In addition, this study shows that key members of metabolic pathways, including AMPK signaling, TGF-β signaling, and insulin signaling, are among the genes hypermethylated after physical exercise in older women.