Exercise Alters DNA?

While browsing the web, an article that was published on March 7th, 2012 by Alice Park, caught my attention- "How Exercise Can Change Your DNA". I have been on an exercise regimen this semester and was curious as to how this could be possible and what effects exercise has on the body overall. It's common knowledge that exercise is good for your body and can reduce the risk of many diseases in the long term, but what does exercise do for us in the short term? Can one workout make any difference? These were some questions that crossed my mind before I began reading this article. According to this article, researchers worked with a group of young men and women that were relatively inactive and had them work out on an exercise bike that measured their maximum activity levels. The researchers then took a bit of muscle from their quadriceps via a biopsy procedure performed under local anesthesia. The biopsy of muscle cells was taken before the participants exercised and once again, about 20 minutes afterward. Results indicated "more genes were turned on in the muscle cells taken after the exercise and the participants' DNA showed less methylation, a molecular process in which chemicals called methyl groups settle on the DNA and limit the cell's ability to access, or switch on, certain genes."

After reading this article, I came across links to other articles with similar connotation and decided to clip these links into my Evernote Notebook in case I wanted to read through them for the purpose of this post. My questions now were related to how methylation occurs exactly- how are these methyl groups removed from the DNA? Are there specific enzymes that can demethylate DNA?

DNA Helix

One of the articles I pulled from my clippings in my Evernote Notebook stated, "the presence (or absence) of methyl groups at certain position on DNA can affect gene expression." This article, written by Ruth Williams, published on March 6th, 2012, also used the same research to show how a "trip to the gym alters DNA". Williams mentions how the research team looked at the methylation status of genes in the small biopsies taken from the muscles of the healthy young men and women before and after they used the exercise bike. They found that, for some genes involved in energy metabolism, such as PGC-1α, PPAR-δ and PDK4, the workout demethylated the promoter regions, extensions of DNA that facilitate the transcription of particular genes. As a control, the genes that were unrelated to metabolism remained unmethylated. So what does this mean exactly? The amount of demethylation at the genes mentioned above, depended on the intensity of the exercise, as those that cycled the hardest showed the greatest gene demethylation. This information is a great finding as it was previously believed that once a cell becomes an adult cell type, such as a muscle cell or a fat cell, it is generally thought that DNA methylation is stable. However, the new research shows that acute exercise changes the methylation status of the genome in actual muscle cells. This information is very exciting to many researchers in the field and it is said that more details will follow within the next few months. However, I want to continue pursuing this subject and see if I can find any more information. My next step was to look into the research abstract, which was published in the journal Cell Metabolism, for additional details.

The overall hypothesis of this study was that exercise, a physiological stressor that is known to alter whole body energy and glucose homeostasis, rapidly alters DNA methylation in skeletal muscle. The effects of a single and acute amount of exercise was studied using metyhlated DNA capture, followed by quantitative PCR and bisulfate sequencing. It is seen in Figure 1 that exercise-induced gene induction is associated with transient alterations in promoter methylation.

Figure 1. Acute Exercise Remodels DNA Methylation (A) LUMA analysis of global DNA methylation. Global CpG methylation analysis of DNA extracted from muscle at baseline (REST) or 20 min after acute exercise (ACUTE EXERCISE). Results are mean ± SE. *p < 0.05 versus REST. (B) Promoter-specific analysis of methylation levels. Methylated DNA Immunoprecipitation followed by quantitative PCR analysis (MeDIP-qPCR) was performed. Ratio between methylated levels at rest and acute exercise is shown. Dashed line symbolically delimitate an equal quantity of methylation at rest and after acute exercise. Results are mean ± SEM for n = 14 subjects. *p < 0.05, **p < 0.01.

The results indicated that acute exercise induces gene-specific DNA hypomethylation in human skeletal muscle. Furthermore, the findings from this study provide evidence that the epigenetic marks across the genome are subject to more dynamic variations than previously realized. Therefore, short 20-minute workouts can make a difference on our DNA and lead to gene activation. This is a great finding for me because sometimes I don't have too much time to workout and opt for a quick, but rigorous, 20-30 minute workout.

Most of the information I found was interesting and helped me understand how exercise can change DNA overall. However, there are still many questions that remain up in the air, which both researchers and I have pondered. This is a very hot topic at the moment and there will be more information to follow in the next few months, which I look forward to following up on.

Citations:

1] Park, A. (2012, March 7). How exercise can change your dna. Retrieved from http://healthland.time.com/2012/03/07/how-exercise-can-change-your-dna/

2] Williams, R. (2012, March 6). A trip to the gym alters dna. Retrieved from http://www.nature.com/news/a-trip-to-the-gym-alters-dna-1.10176

3] Lim, H. N., & Oudenaarden, A. V. (2007). A multistep epigenetic switch enables the stable inheritance of dna methylation states. In Nature Genetics Retrieved from http://www.nature.com/ng/journal/v39/n2/pdf/ng1956.pdf

4] Barrès, R., Yan, J., Egan, B., Treebak, J., Rasmussen, M., Fritz, T., Krook, A., & Zierath, J. (2012). Acute exercise remodels promoter methylation in human skeletal muscle. In Retrieved from http://www.sciencedirect.com/science/article/pii/S1550413112000058