There's more to your DNA than your DNA. We are now becoming aware of the epigenome. While DNA controls you, your epigenome may help control your DNA, or rather, it can have an extensive impact on how your DNA is expressed. The epigenome consists of changes in the structure of your DNA, how it is packaged, what parts of it are available for expression into RNA and proteins. For example, adding methyls to DNA tends to decrease the gene expression of that DNA segment, while taking away methyl groups increases it. The cool thing about epigenetics is that the methylation can vary from tissue to tissue, controlling how different genes are expressed in say, liver vs spleen.

(I can't wait til Jonathan Coulton writes a song about the epigenome)

One of the most interesting things about the epigenome is that you can pass it along in the germline. To your kids. So in theory, if you had methylation in certain parts of your genome, your kids could as well. But we're starting to realize that epigenetics is more malleable than that.

Take muscle tissue for instance. Gene expression in muscle tissue can change the efficiency of glucose metabolism by muscle. And glucose metabolism has a very large effect on many bodily processes, include weight gain and problems like cardiovascular disease and type II diabetes. Muscle itself is very plastic, and responds quickly to changes in the environment (which for a muscle, means increases and decreases in exercise or how many calories are getting in). We know that exercise can change gene expression in muscle, but can it also change the epigenome? While immediate changes in gene expression can be very short, changes to the epigenome indicate much longer-term changes. Could bouts of exercise influence the methylation of muscle, and thus have long-term effects?

Barres et al. "Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle" Cell Metabolism, 2012.

The cool thing is that the authors of this study were able to do large sections of this study in humans. Humans, at least, who did not object to getting muscle biopsies.

They took 14 sedentary humans and had them exercise to fatigue (a pretty difficult exercise bout). They biopsied the muscles before and after the exercise, and looked to see what the methylation in the muscle looked like.

What you can see here is that the acute bout of exercise decreased the methylation in the muscle tissue. When they looked a little closer, the authors found that the methylation was particularly decreased in the promotor regions of metabolically related genes. Many of these promotor regions, which directly control the expression of a gene, show changes in methylation during type II diabetes. After exercise the methylation in these promotor regions was decreased, which could result in more gene expression of those genes, and thus result in changes in metabolism.

Further studies showed that this change in methylation depended on exercise intensity. In a group of mice exposed to low or high intensity exercise, only the high intensity produced the gene methylation changes seen in humans.

So we know that exercise is changing DNA methylation (and that this can be changed in response to a single acute bout of exercise), but what is the mechanism? The authors hypothesized that it might have to do with changes in calcium influx into the muscle cells starting an activation of activities leading to changes in methylation. So they applied caffeine to cells in culture. While pharmacologists like me usually think of caffeine as an adenosine receptor antagonist, in muscle cells it can increase calcium influx into the cell. And they found that caffeine application had the same effect that acute exercise did, reducing methylation and changing gene expression. If the authors used another drug (dantrolene) to block the calcium influx, they could block the effects of caffeine (whether caffeine works this way during human consumption? I don't know, the effects would probably be a good bit milder than those on cells in a dish, to say the least).

We know that increases in methylation in muscle cells are associated with things like insulin resistance, so it's possible that decreases in methylation could explain some of the protective effects of exercise. And it's very interesting to see that the authors got changes in methylation after a single exercise exposure. Of course, it would interesting to see if these changes persist with chronic exercise, and whether caffeine ingestion in humans in normal amounts produces similar changes, but I imagine maybe the humans in these studies weren't up for the biopsies. But it's an interesting study, helping us begin to see how changes in the epigenome, caused by changes in our own behaviors, might begin to impact our health in the long term. It makes me want to go for a workout.

Barrès, R., Yan, J., Egan, B., Treebak, J., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D., & Zierath, J. (2012). Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle Cell Metabolism, 15 (3), 405-411 DOI: 10.1016/j.cmet.2012.01.001