In today’s busy world, it can be hard to find time to exercise. Various factors, such as sedentary jobs and the presence of TV and video games at home, can contribute to inactivity in adults and kids alike. Both fitness experts and medical professionals encourage taking small steps toward a more active lifestyle, such as using the stairs instead of the elevator, or biking instead of driving to work. There is already plenty of evidence demonstrating the health benefits of an active lifestyle, including lowering the risk of cardiovascular disease and improving mood, but perhaps some surprising new findings about the biological effects of exercise will provide an extra motivational boost to get you to the gym. These findings indicate that exercise actually makes specific changes to our DNA and can affect the function of genes in fat and muscle cells.
How can DNA be changed?
The idea that DNA can be altered by something like exercise might seem a bit confusing since DNA is inherited from one’s parents. However, inheritance only provides the genetic blueprint, or the physical DNA sequence, it is up to the cells of the body to determine what to do with it. This is a complex task, especially as each cell has so much DNA to manage. If an average cell’s DNA were laid out in a straight line, it would stretch nearly 6.5 feet, which is approximately 100,000 times larger than an average cell, indicating that there is a tremendous amount of genetic information that each cell must carefully control (1). In order for all of this material to fit inside such a small space, it has to be packaged into a compact structure, which is accomplished by tightly coiling DNA around spherical proteins called histones (Figure 1). Cells take advantage of this coiling to control which genes are expressed, or “switched on” and used to make protein that will function within the cell.
For a gene to be used to make protein, it needs to be physically accessible to the machinery of the cell. That accessibility is controlled by how tightly the DNA is looped around histones. To switch on a gene, the coil needs to be loosened, whereas tightening the coil can repress or “switch off” genes. Scientists working to understand how cells control this coiling have discovered small molecules that attach to DNA and affect the tightness of the coil (2). One of these molecules, called a methyl group, usually tightens the coil of whatever gene it binds, causing it to be repressed (Figure 1). This binding event is called DNA methylation. A new field of research called epigenetics (meaning “above” or “on top of” the genome) has emerged to study this type of DNA regulation, and has found that a variety of factors can cause small molecules to bind DNA and thereby regulate gene expression, including diet, parental care, and possibly even environmental toxins (3). Some of these binding events have even been discovered to be heritable, that is, capable of being passed on to offspring. This means that even though one’s DNA sequence cannot be changed, environmental factors can play a role in changing gene activity. Recent studies conducted by two groups in Sweden suggest that exercise could be another important epigenetic factor, regulating DNA methylation in multiple types of cells.
Figure 1. DNA (purple) is tightly coiled around histones (blue) to fit within the cell. A loosely coiled gene (pink) can be expressed because it is physically available to the cellular machinery that makes protein (A). An event, such as exercise, can cause methyl groups (green) to bind to genes, which is known as DNA methylation (B). This methylation causes bound DNA to be more tightly coiled around histones, repressing the gene by making it inaccessible to the protein-making machinery (C). Figure adapted from <http://commons.wikimedia.org/wiki/File:Epigenetic_mechanisms.jpg>.
Does exercise affect DNA?
Researchers at Lund University in Sweden decided to investigate whether cardiovascular exercise can make changes to DNA (4). They recruited 23 healthy, but sedentary, men in their mid to late thirties and asked them to take one spinning class and two aerobics classes every week for a six month period. The men were asked not to change anything else about their lifestyle, including their diet and daily activity level. As expected, the men had smaller waists, improved blood pressure, and lower weights at the end of the study, despite only making it to two exercise classes a week on average. Researchers also collected a sample of fat cells from the men before and after the six-month program. They then compared the fat cells before and after regular exercise to look for changes in DNA methylation. They found that thousands of genes showed altered methylation patterns after exercise, with most genes adding methyl groups and a small number losing methyl groups. They also discovered that nearly 200 of these methylated genes were functionally repressed, including genes previously linked to obesity or type 2 diabetes. While it is not yet known how long these changes persist or what they specifically do to fat cells, these intriguing data suggest that exercise may exert beneficial effects by either turning off or preventing the activation of potentially harmful genes.
Fat cells aren’t the only type of cells that exhibit changes in DNA methylation after exercise. Changes in methyl group binding have also been observed in muscle cells. One recent study conducted at the Karolinska Institute in Sweden showed that methyl groups were removed from specific genes in muscle cells immediately after exercise, particularly from genes that regulate cellular metabolism, which suggests that these genes were being switched on; however, this effect was temporary and cells returned to baseline a few hours later (5). The same Lund University lab that studied fat cells also examined changes in DNA methylation in muscle cells after the six-month program. In this case, the researchers found that over 100 genes showed reduced methylation, indicating activation of gene expression (6). Some of the activated genes were those involved in providing energy to the cell, such as genes involved in mitochondrial function. Muscle cells did have more mitochondria after six months of exercise, which the researchers suggest could be related to the reduced methylation, although that remains to be proven. Further studies investigating how cells respond to changes in methylation and whether DNA in other cell types is affected by exercise will enable better understanding of this phenomenon.
These studies suggest that exercise does affect DNA, and indicate that changes in gene function could be related to the beneficial effects of exercise on health. Since dietary status has also been shown to modify genes through epigenetic means, it is becoming increasingly clear that living a healthy lifestyle could have a direct impact on DNA. However, there is still much work to be done to understand what these genetic modifications mean biologically, as well as whether they are maintained if exercise ceases, and if these modifications can be inherited. Future research in the exciting field of epigenetics may begin to provide answers to these questions, in addition to important information about how other environmental factors might shape DNA.
Emily Lehrman is a Ph.D. candidate in the Program in Neuroscience at Harvard Medical School.
References:
[1] Annunziato, Anthony T. “DNA Packaging: Nucleosomes and Chromatin.” Scitable, 2008. http://www.nature.com/scitable/topicpage/dna-packaging-nucleosomes-and-chromatin-310. 14 October, 2013.
[2] Hurley, Dan. “Grandma’s experiences leave a mark on your genes.” Discover Magazine, May 2013. http://discovermagazine.com/2013/may/13-grandmas-experiences-leave-epigenetic-mark-on-your-genes#.Ulyv6iSE4hp. 14 October, 2013.
[3] Watters, Ethan. “DNA is not destiny.” Discover Magazine, November 2006. http://discovermagazine.com/2006/nov/cover#.UlyfUSSE4ho. 14 October, 2013.
[4] Ronn, T., Volkov, P., Davegardh, C., Dayeh, T., Hall, E., Olsson, A., …Ling, C. (2013). A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genetics 9(6): e1003572. doi: 10.1371/journal.pgen.1003572.
[5] Barrès, R., Yan, J., Egan, B., Treebak, J.T., Rasmussen, M., Fritz, T., …Zierath, J.R. (2012). Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle. Cell Metabolism 15(3): 405-411.
[6] Nitert, M.D., Dayeh, T., Volkov, P., Elgzyri, T., Hall, Nilsson, E., …Ling, C. (2012). Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes 61(12): 3322-32