Working out alters DNA

DNA

 

Exercise is found to alter the methylation of cell metabolism related promoter regions in human subjects.

 

DNA expression is a complicated process that has yet to be completely unraveled by geneticists. One way DNA expression is regulated is through methylation. Methylation involves attachment of methyl groups (-CH3) to the DNA, inhibiting its expression. When a promoter region becomes heavily methylated expression of the corresponding gene becomes inhibited.  Methylation plays a role in cell differentiation; specialized cells are methylated in characteristic patterns. Geneticists previously believed that methylation is permanent within an adult cell. However, a recent study first published in Cell Metabolism and featured in Nature found that exercise alters methylation (Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle, 2012. Romain Barres, et al.).

Exercise was found to demethylate cell metabolism promoter regions in sedentary men and women following acute exercise. In the study muscle biopsies were performed on the subjects following acute exercise at 40% and 80% of maximum. The figure below shows that methylation was significantly reduced in the muscle after acute exercise. In addition, promoters for genes involved in energy metabolism where analyzed in muscle fibers. The figure shows that for all the energy metabolism genes (PGC-1a, TFAM, PPAR, CS and PDK4) methylation was found to be reduced in their respective promoters.  This was not the case for muscle specific genes MEF2A and MYOD1 as well as the muscle “housekeeping” gene GAPDH.

Screen Shot 2012-12-15 at 8.40.29 AM

Acute Exercise Remodels DNA Methylation: (A) Global CpG methylation analysis at rest (REST) and 20 minutes after acute exercise (ACUTE EXERCISE). (B) Ratio of methylation after acute exercise and at rest, dashed line represents no change. *p<0.05, **p<0.01

Similar changes in gene expression were observed following exercise. Exercise increased the gene expression of the demethylated genes as measured by mRNA levels. The intensity of exercise affected the significance of demethylation. Working out at 40% of maximum effort produced less of an effect than at 80% of maximum effort. Within three hours of the exercise effort most of the demethylation effect observed immediately post exercise session had disappeared. Isolated mouse soleus were observed to determine whether exercise-induced factors were needed to cause the methylation changes seen in the human subjects. The mouse muscle fibers contracted ex vivo showed methylation changes as shown by the figure below. This means that external factors are not needed to change the methylation, but the contracting fiber itself causes the changes. Gene expression peaked three hours after the ex vivo muscle contractions. Meanwhile, hypomethylation occurred 45 minutes after ex vivo muscle contractions.

Screen Shot 2012-12-17 at 11.24.22 PM

Muscle Contraction Induces Hypomethylation: Gene expression (A) and promoter methylation (B) in isolated mouse soleus. *P<0.05

 

The study also found that large doses of caffeine induced hypomethylation. The mechanism, the authors believe, is through caffeine-induced calcium release from sarcoplasmic reticulum (the cause of contraction according to the sliding-filament theory). Because the gene expression and methylation patterns differed slightly, gene expression is influenced, but not completely controlled by, DNA methylation.

This study has ramifications beyond exercise. This introduces the novel concept that the environment can influence DNA methylation in non-dividing, somatic, adult cells. Epigenetic marks across the genome are subject to greater disparity than formerly realized.