It’s a well-known fact that exercise improves health. Whilst decreasing the risk of basically all chronic illnesses – including type 2 diabetes, cancer, cardiovascular diseases, and neurological conditions – exercising also improves our mood, helps us better manage stress, leads to better mental health, lowers our overall risk of mortality, and the list of the benefits of exercise goes on for a while. Whilst the benefits of exercise are easily seen and proven, the mechanisms at play are not entirely understood. With this in mind, scientists Williams et al. (2021) concluded that the benefits of exercise may partly result from structural changes to our DNA, also known as ‘epigenetic’ changes. They present and conclude that this process contributes to the beneficial effect of exercise on human health.
DNA is a long molecule within our cells, which contains our unique genetic code and holds the instructions for making all the proteins in our bodies (like a recipe book for cooking a meal or an instruction manual for assembling a bike). Some sections of our DNA are genes, which are the instructions to build proteins (the building blocks for the body), while other sections are called enhancers, which regulate which genes are switched on or off, when, and in which tissue. Epigenetics relates to the study of how your behaviours and environment can cause changes that affect the way your genes work. The scientists found, for the first time, that physical exercise rewires the enhancers in regions of our DNA that are known to be associated with the risk to develop disease.
To test out their hypothesis that exercise alters the activity of enhancers in skeletal muscle tissue, which then regulates the expression of genes that contribute to the benefits of exercise on our health, the scientists recruited 8 healthy young men (average age of 23) and put them through a six-week endurance exercise programme. Biopsies of the young men’s thigh muscle were collected before and after the exercise intervention (pre- and post-training biopsies). The endurance exercise programme was performed five days a week, with all participants completing all training sessions. After the last bout of exercise, participants rested for 4 days before their post-training sample was collected. The scientists then used all this information from the participants to identify genes regulated by exercise training in human skeletal muscle, and examined if changes in the epigenetic signature of their DNA occurred after training.
The scientists found that following completion of the exercise programme, the structure of many enhancers in the skeletal muscle of the young men had been changed. By connecting the enhancers to genetic databases, they found that many of the regulated enhancers have already been acknowledged as hotspots of genetic variation between people – hotspots that have been linked with human disease. Furthermore, the scientists speculate that the benefits of exercise on organs far from muscle, like the brain, may mainly by mediated by regulating the secretion of muscle factors. Specifically, they discovered that exercise remodels the activity of skeletal muscle enhancers that are associated with cognitive abilities, which allows for the identification of exercise training-induced secretions of muscle factors targeting the brain.
Overall, their findings suggest that enhancers remodelled after exercise training may have a role to play in disease prevention, especially of cardiovascular and cognitive disorders, by regulating transcription of enhancer connected genes. Their results give insight into the possible contribution of exercise-induced epigenetic remodelling at enhancer regions on the phenotype (the physical characteristic of a person). And so, this provides evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise, and the modulation of disease risk in humans.
Original Paper: Williams., K, Carrasquilla., G.D., Ingerslev., L.R., et.al. (2021) “Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health.” Science Direct. doi.org/10.1016/j.molmet.2021.10129
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Edited by Cyrus Rohani-Shukla