Exercise Training Epigenetically Benefits Overall Health

There’s no question that exercise is good for you, not only for developing a great physique but for overall health. Some would even say that regular exercise, combined with proper nutrition, is better at preventing and treating certain diseases than many pharmacological interventions.

Even so, medical experts are still trying to determine exactly how physical fitness affects the chemical make-up of the body, especially regarding how it reduces the risks of developing chronic illnesses like cancer, cardiovascular disease, diabetes, and several neurological conditions.

Prior studies have shown that the beneficial effects of exercise are in part driven by changes made in the skeletal muscle. These changes alter the expression of genes that control metabolic and molecular responses, which also systematically affect the entire body by sending signals to distant tissues like the brain and liver. The mechanisms involved in this process, however, have been poorly understood. But newer research is finding that epigenetic factors likely link exercise to having a lower risk for many diseases.  

In a recent study completed at the University of Copenhagen (UCPH), a group of scientists set out to test the hypothesis that exercise done over a set time period consistently could alter the gene activity of enhancers in the skeletal muscle tissue, thereby positively affecting human health. Published in the journal Molecular Metabolism, their analysis was successful and pointed out a mechanism that supports the well-known benefits of exercise.

The study was administered to a group of healthy young men who participated in a 6-week endurance training program. Before and after the exercise intervention, muscle biopsies were collected from the thigh of each man. Then, genome-wide mapping of the positions and activities of enhancers in the muscle samples was performed by screening for changes in histone modifications via ChIP-sequencing.

Enhancers are short regions of the DNA that are bound by multiple transcription factors (TFs), and they are largely responsible for controlling gene expression by physically connecting with promoters. Enhancer regions help increase transcription, and they do not necessarily need to be close to the gene they enhance. To date, millions of enhancers across hundreds of human cell lines have been identified, and their activity is highly dynamic and subject to epigenetic regulation.

The results of their analysis showed that exercise training caused structural changes or rewiring in several of the skeletal enhancers. Using a genetic database, the UCPH researchers overlapped the position of these enhancers with established genetic variants and found that many of them coincided with ones associated with human diseases. 

“By connecting each enhancer with a gene, we further provide a list of direct targets that could mediate this effect,” explains author and professor Romain Barrès of the Novo Nordisk Foundation Center for Basic Metabolic Research at UCPH.

The researchers also found that the exercise was advantageous to organs distant from the skeletal muscle tissue, possibly due to signals being released from the tissue into the bloodstream.

For instance: exercised-remodeled enhancer activity found in skeletal muscles associate with improved cognitive performance, suggesting that regular physical activity induces muscles to release factors targeting the brain.

“Our data provides evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans,” said Kristine Williams, first author of the study and assistant professor of the Novo Nordisk Foundation Center for Basic Metabolic Research at UCPH.

There’s much more to be learned regarding the factors involved in how exercise lowers disease risk. This study serves as an essential resource, as it gives insight into the mechanisms involved in the process and how cells communicate in different tissues. The hope is that future studies will build upon this understanding, potentially allowing for the development of medicines that mimic the cell signals from exercise.

Source: Kristine Williams, et al. (2021). Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health. Molecular Metabolism.

Reference: Exercise improves health through changes on DNA, University of Copenhagen – The Faculty of Health and Medical Sciences. July 26 2021.