Study: Physical exercise improves brain and other organ health through epigenetic changes

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Some sections of our DNA are genes, which are instructions for building proteins, while other sections – called enhancers – regulate which genes are turned on or off, when, and in which tissue. New research from the University of Copenhagen and the Karolinska Institutet provides evidence of a functional link between the epigenetic rewiring of activators to control their activity after physical training and the modulation of disease risk in humans.

Exercise training rewires activators in regions of our DNA that are known to be associated with the risk of developing disease. Image credit: Sasin Tipchai.

“Regular physical activity decreases the risk of several common disorders such as cardiovascular disease, type 2 diabetes, cancer and neurological disorders, as well as the overall risk of mortality,” said Professor Romain Barrès of the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen and colleagues.

“The beneficial effects of physical training on human health are in part due to the adaptations of skeletal muscle tissue.”

“Exercise-induced adaptations include coordinated changes in gene expression controlling substrate utilization and metabolic efficiency in skeletal muscle.”

“In addition to the adaptations that occur in skeletal muscle cells, exercise exerts systemic effects on whole body homeostasis by triggering the release of soluble factors from the muscle that signal to distal tissues, such as the brain, liver and adipose tissue. “

“The mechanisms by which training-induced adaptations of skeletal muscles orchestrate positive whole-body effects are poorly understood.”

“We hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle and that this remodeling contributes to the beneficial effects of exercise on human health.”

For the study, the researchers recruited eight healthy Caucasian men (average age 23) and put them through a six-week endurance exercise program.

They took a biopsy of their thigh muscle before and after the exercise procedure and looked at whether any changes in their DNA epigenetic signature occurred after the workout.

They found that after completing the endurance training program, the structure of many activators in the skeletal muscle of young men was altered.

By connecting enhancers to genetic databases, scientists have found that many regulated enhancers have already been identified as hot spots of genetic variation between individuals.

“Our results provide a mechanism for the known beneficial effects of exercise,” said Professor Barrès.

“By connecting each activator to a gene, we further provide a list of direct targets that could mediate this effect.”

The authors speculate that the beneficial effects of exercise on organs remote from muscle, such as the brain, may be largely mediated by regulating the secretion of muscle factors.

In particular, they found that exercise reshapes enhancing activity in skeletal muscle that is linked to cognitive abilities, which paves the way for the identification of secreted muscle factors induced by exercise training targeting the brain. .

“Our data provide evidence of a functional link between the epigenetic rewiring of activators to control their activity after exercise and the modulation of disease risk in humans,” said Dr Kristine Williams, also of the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.

The results are published in the journal Molecular metabolism.

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Kristine williams et al. The epigenetic rewiring of skeletal muscle activators after physical training plays a role in whole body function and human health. Molecular metabolism, published online July 10, 2021; doi: 10.1016 / j.molmet.2021.101290


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