Karolinska Institute researchers find that training alters DNA.
Why is exercise healthy? Maybe because it changes DNA and affects expression of genes in physiology and metabolism, according to new research from the Karolinska Institute. The study made the news, in part because of a creative design.
Exercise changed DNA methylation and gene expression
In the study, 23 volunteers rode exercise bicycles four times a week, using only one leg. Maléne Lindholm, lead author on a paper about the work, explains that just being in an exercise study makes people think about their health.
“They sometimes change other habits like diet or sleep,” she says. The study design meant participants were their own controls. If they started eating better, for example, their entire body would be affected. Physiological differences in their legs were assumed to be from training.
After three months, the researchers compared muscle biopsy samples from active and less active legs and found that exercise changed DNA methylation and gene expression. DNA methylation is epigenetic: it affects the activity, not the sequence of genes. The epigenetic and expression changes were mainly in chromosomal regions and genes linked to muscle development and metabolism.
Simple exercise can change the epigenome
The work contributes to our evolving view of DNA methylation. This and other epigenetic modifications used to be considered stable, changing only over the long term.
“We found that simple exercise can change the epigenome,” says Lindholm, a PhD student in Professor Carl Johan Sundberg’s group, Department of Physiology and Pharmacology, Karolinska Institute. The study also highlighted the importance of enhancers in the exercise response. Enhancers are regulatory DNA sequences that control genes from a distance, unlike promoters, which are adjacent to the genes they control. “We found little difference in promoters,” says Lindholm. “Most changes were in enhancers.”
The results have many applications, says Lindholm, all in the far future. If we know the mechanism of exercise benefits, we might induce the same changes in someone who can’t exercise, for example because of paralysis. The information might be used to personalize training programs. For public health reasons, we want people to exercise, says Lindholm. Providing individual molecular responses to training might be a good motivator.
For now, the researchers are continuing to study samples from the project, says Lindholm, they’re looking at other epigenetic markers such as histone modifications. The team also conducted a followup study. The original volunteers returned after nine months without training. This time, they exercised both legs. “We’re interested in skeletal muscle memory,” says Lindholm. “We’re seeing if training in the past changes the muscle response, for example, if earlier training gives an advantage.” A paper on gene expression and muscle memory is expected soon.
Lindholm ME, Marabita F, Gomez-Cabrero D, Rundqvist H, Ekström TJ, Tegnér J, Sundberg CJ. An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training. Epigenetics. 2014 2;9(12):1557-69.