Abstract
Lifelong regular physical activity is associated with reduced risk of type 2 diabetes (T2D), maintenance of muscle mass and increased metabolic capacity. However, little is known about epigenetic mechanisms that might contribute to these beneficial effects in aged individuals. We investigated the effect of lifelong physical activity on global DNA methylation patterns in skeletal muscle of healthy aged men, who had either performed regular exercise or remained sedentary their entire lives (average age 62 years). DNA methylation was significantly lower in 714 promoters of the physically active than inactive men while methylation of introns, exons and CpG islands was similar in the two groups. Promoters for genes encoding critical insulin-responsive enzymes in glycogen metabolism, glycolysis and TCA cycle were hypomethylated in active relative to inactive men. Hypomethylation was also found in promoters of myosin light chain, dystrophin, actin polymerization, PAK regulatory genes and oxidative stress response genes. A cluster of genes regulated by GSK3β-TCF7L2 also displayed promoter hypomethylation. Together, our results suggest that lifelong physical activity is associated with DNA methylation patterns that potentially allow for increased insulin sensitivity and a higher expression of genes in energy metabolism, myogenesis, contractile properties and oxidative stress resistance in skeletal muscle of aged individuals.
Highlights
Regular physical activity promotes health and longevity
In addition to rate-limiting enzymes in glycolysis and TCA cycle, we found that promoter regions of genes encoding important insulin responsive proteins involved in carbon metabolism were hypomethylated in active compared with inactive men, suggesting that promoter methylation links regulation of metabolic pathways with higher capacity for insulin action in skeletal muscle
This study presents a library of changes in global DNA methylation patterns in skeletal muscle that occurs during lifelong physical activity which serves as a resource for future research
Summary
Regular physical activity promotes health and longevity. The Harvard Alumni Health Study revealed that regular exercise reduces mortality in elderly men[1] and in the Norwegian male population, half of the people with high physical fitness reach the age of 85 compared to only one fourth among men with low physical fitness[2]. The aim of the present study was to investigate the impact of lifelong physical activity on global DNA methylation patterns in muscle tissue of 16 healthy aged men with an average age of 62 years. Eight of these subjects had a physically active lifestyle with regular exercise their entire lives and eight subjects were healthy but with a physically inactive lifestyle. Our data reveal physical activity level dependent epigenetic modifications in genes involved in muscle structural dynamics, energy metabolism, and predisposition to T2D This suggests that the level of physical activity throughout life affects DNA methylation of genes within cellular pathways and metabolic processes in skeletal muscle
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