We know that exercise has the power to change our outward shape. But the findings of a new study offer insight into how it changes the shape of our inner workings at the genome level and how that could lead to improved health and fitness.

The human genome serves as a kind of control panel in which the switches are the genes, constantly turning on or off, dependent on the biochemical signals they receive from the body. When genes are activated, they express proteins that cause physiological responses at some other point in the body.

It’s known that certain genes become active as a result of exercise, while others “pipe down”. Little was known, however, about exactly how those genes are triggered by exercise.

In recent years, science has looked at epigenetics, a process whereby temporary biochemical changes in the genome – though not in the DNA itself – are caused by various kinds of environmental impact. One such type of epigenetic change is methylation, in which a methyl group is added to or removed from a base in the DNA molecule without affecting the original DNA sequence – roughly analogous to the role of changing the software for a given piece of hardware.

A new study from Karolinska Institute in Sweden shows that long-term endurance training in a stable way alters the epigenetic pattern in the human skeletal muscle. The researchers also found strong links between these altered epigenetic patterns and the activity in genes controlling improved metabolism and inflammation – findings that could have some implications for preventing and treating some diseases as well as insight into how to maintain good muscle function throughout the lifespan.

The study observed 23 young and healthy men and women who performed supervised one-legged cycling, using the untrained leg as a control. The volunteers took part in 45 minute training sessions four times per week during a 12-week period. Muscle performance was measured in both legs before and after training. Measurements also took the form of skeletal muscle biopsies, markers for skeletal muscle metabolism, methylation status of 480,000 sites in the genome, and activity of over 20,000 genes.

Results show that there were strong associations between epigenetic methylation and the change in activity of a total of 4,000 genes. Genes associated to genomic regions in which methylation levels increased, were involved in skeletal muscle adaptation and carbohydrate metabolism, while a decreasing degree of methylation occurred in regions associated to inflammation.

One novel and potentially far-reaching finding of the study was that most of the epigenetic changes occurred in regulatory regions of the human genome. These “enhancer” sequences in the DNA are often located far from the genes they regulate compared to so-called promoter regions, which previously were considered to be in control of most gene activity.

The findings, the researchers say, could lead to a better understanding and treatment of diseases such as diabetes and cardiovascular disease. The team also observed epigenetic differences between male and female skeletal muscle, something that could have bearing on developing gender-specific treatments.


  1. Lindholm, Maléne E., et al. “An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training.” Epigenetics just-accepted (2014): 00-00.



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