SIB # 462 - Change your DNA? Yes!

The Study: Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health.

Overview: This study looked at changes in the human genome of a group of “young  sedentary men before and after 6 weeks of endurance exercise.”

 Key Points:

 ·         It is well known that regular physical activity can benefit a number of common disease states such as cardiovascular disease, adult onset diabetes, cancer, neurological conditions and even the overall risk of mortality.   

·         The exact mechanisms by which exercise exerts these benefits remain unclear.  

·         Although some portions of our DNA carry the blueprint for building various proteins, there are also large portions of our genetic code, known as “enhancers” which regulate when and which genes are to be switched on and off.  

·        This study sought to better understand genetic mechanisms by which exercise might confer benefits to other organs and systems beyond the musculoskeletal system.   

·         This was a small study of eight young, physically inactive males each of whom underwent a 6-week endurance training program consisting of supervised ergocycle exercise for 60 min, five days a week, at 70% of each participant’s maximal aerobic capacity.  

·         Muscle biopsies were collected from all participants both before and after the six week exercise program and a VO2 max test was performed to determine how well each subject was able to use oxygen during exercise. 

·         At the end of the six week training period the average aerobic capacity was increased by 20%. 

·         The authors also performed genome wide mapping of the biopsy samples after exercise training and identified “thousands of enhancers” that were remodeled over the course of the six week exercise intervention.  

·         Then, by connecting the locations of these remodeled enhancers to genetic databases, they discovered that many of the remodeled enhancers were connected to areas of the genome already identified as “hotspots” associated with human disease. 

Results:  

Although this study looked at genetic samples obtained from muscle tissue, the authors found that many of the remodeled enhancers were related to disease categories which were far removed from the musculoskeletal system.  

Remodeled enhancers included areas related to blood coagulation, platelet functions, cardiovascular disease, glucose metabolism, renal function and even cognitive performance.

  Author’s Conclusions: 

“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,” says Assistant Professor Kristine Williams, the lead author of this study.” (emphasis ours) 

“our study constitutes a powerful resource for the identification of key factors involved in the beneficial effects of endurance training on human health.”

Reviewer's Comments: Most of us were educated to believe that our entire genetic code was basically carved in stone. This paper contributes to an ever growing knowledge of epigenetics demonstrating that certain portions of the code may be subject to “remodeling” with resulting up (or down) genetic regulation according to lifestyle and environmental factors within our control.

 Reviewer:  Mark R. Payne DC

Reference:      K Williams, G. Carrasquilla, L Ingerslev et al. Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health. J. Molecular Metabolism. Pre publication (scheduled for Nov. 2021).

 Link: https://www.sciencedirect.com/science/article/pii/S2212877821001356