Epigenetics of Skeletal Muscle Altered by Endurance Training

We all know that exercise is good for us, but researchers at the Karolinska Institutet in Sweden are exploring the epigenetic impact good exercise has on our skeletal muscles. We have previously touched on the effects of epigenetic changes on the development of diseases such as diabetes and cardiovascular disease. In a recent study in Epigenetics, long-term endurance training has been shown to affect the epigenetic pattern present in the human skeletal muscle. The changed epigenetic patterns were shown to affect the activity of genes that control inflammation and metabolism. The findings of this study could improve treatment and prevention of diseases like diabetes, obesity, and heart disease.

“It is well-established that being inactive is perilous, and that regular physical activity improves health, quality of life and life expectancy,” said Professor Carl Johan Sundberg, of the Department of Physiology and Pharmacology and the Principal Investigator of the research. “However, exactly how the positive effects of training are induced in the body has been unclear. This study indicates that epigenetics is an important part in skeletal muscle adaptation to endurance training.”

DNA methylation is perhaps one of the most common and well-studied epigenetic mechanisms. It describes the addition or removal of a methyl group to the DNA without changing the underlying genetic code- or genotype. The current study investigated DNA methylation patterns in the skeletal muscles of individuals who underwent endurance training.

Twenty-three healthy and young men and women were supervised when they performed one-legged cycling for 45 minutes four times a week as part of the 3-month study. Both legs were measured before and after training and the untrained leg was used as a control. After performing skeletal muscle biopsies, the researchers looked at markers for skeletal muscle metabolism, methylation status, and gene activity. They assessed over 20,000 genes and looked at 480,000 genomic sites.

The research team found that epigenetic DNA methylation was strongly connected to the change in the activity of 4,000 genes. In certain genomic regions where methylation levels were found to increase, the related genes are known to take part in carbohydrate metabolism and skeletal muscle adaptation. The areas of the genome in which the researchers found a decrease of DNA methylation were associated with genes linked to inflammation.

The significant difference in DNA methylation status of the trained leg skeletal muscles versus untrained was “predominantly observed in enhancers, gene bodies and intergenic regions and less in CpG islands or promoters.” The fact that most of the epigenetic alterations were found to occur in the genome’s regulatory regions, or enhancers, is an interesting and novel finding that could be very important to future epigenetic studies. These enhancers, or specific DNA sequences, are situated far from the genes that they regulate, as opposed to the promoter regions, which are thought to control a majority of the activity of the genes.

“We found that endurance training in a coordinated fashion affects thousands of DNA methylation sites and genes associated to improvement in muscle function and health,” said Carl Johan Sundberg. “This could be of great importance for the understanding and treatment of many common diseases such as diabetes and cardiovascular disease, but also for how to maintain a good muscle function throughout life. Interestingly, we also saw that there were epigenetic differences between male and female skeletal muscle, which may be of importance to develop gender specific therapies in the future.”

Source: Maléne E Lindholm, Francesco Marabita, David Gomez-Cabrero, Helene Rundqvist, Tomas J Ekström, Jesper Tegnér, Carl Johan Sundberg. An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training. Epigenetics. 2014.

References: Karolinska Institutet. Long-term endurance training impacts muscle epigenetics. 2014.