The Beneficial Effect of Exercise on DNA Methylation
As difficult as it may be to drag ourselves out of bed in the morning to go for a run or fit in a quick trip to the gym after work, regular exercise is essential for a healthy life. Research has shown that regular physical exercise reduces the risk of type 2 diabetes and the development of cardiovascular diseases later in life . But while the benefits of exercise are clearly evident, little is known about how exercise influences the epigenetic regulation of genes, which may be responsible for its beneficial effects. In a new study published in Scientific Reports, Sailani and colleagues asked how lifelong regular physical exercise impacts DNA methylation patterns across the genome.
In their study, the authors assessed overall DNA methylation patterns in muscle tissue from 16 men ages 60 to 65. Half of the men had led physically active lifestyles, while the other eight had been inactive. The authors found that while men in both groups had similar heights and weights, the men from the inactive group had a 39% higher percentage of body fat, 13% lower lean mass, and had a 41% lower cycling endurance.
When the authors looked at the differences in DNA methylation, they found that DNA methylation levels were significantly reduced at promoter regions in muscle from active men compared to inactive men. DNA methylation levels at other regions of the genome – CpG islands, introns, and exons – showed no difference. DNA methylation commonly represses gene expression, and a reduction in DNA methylation, especially at a gene promoter, will likely lead to the increased expression of that gene.
Interestingly, the authors found that many of the genes with reduced methylation at their promoters encode proteins that are important for energy metabolism, insulin-response, muscle growth, and regulating oxidative stress. In terms of energy metabolism, they found that proteins involved in the steps of glycolysis, which produces energy for the cell, not only had reduced methylation at their gene promoters but also had increased protein expression in muscles of active compared to inactive men. The authors saw a similar result for promoters of genes encoding insulin-responsive proteins and proteins involved in the oxidative stress response, SOD2 and Catalase.
This work demonstrates that lifelong physical activity affects the epigenetic landscape of particular genes in muscle tissue, and that these genes are involved in functions that promote muscle growth and health. In future studies, the influence of physical activity on the epigenetics of female subjects, and more subjects overall, should also be investigated. Additional work is needed to tease out the effect of decreased DNA methylation of these gene promoters on overall health of the individual, but this study provides a useful starting point and an encouraging push to roll out of bed and take a quick walk around the block.
Original article: Sailani MR, Halling JF, Moller HD, Lee H, Plomgaard P, Pilegaard H, Snyder MP, Regenberg B (2019). Lifelong physical activity is associated with promoter hypomethylation of genes involved in metabolism, myogenesis, contractile properties and oxidative stress resistance in aged human skeletal muscle. Scientific Reports, 9(1):3272. doi: 10.1038/s41598-018-37895-8.
 Cartee GD, Hepple RT, Bamman MM, Zierath JR (2016). Exercise Promotes Healthy Aging of Skeletal Muscle. Cell Metab, 23: 1034–1047.