Exercise changes chemical marks on DNA

In collaboration with the Karolinska Institutet, Sweden

The underlying genetic code stays the same. However, the DNA molecules within the muscle cells get chemically and structurally altered in very particular ways, by gaining or losing marks of methyl groups on certain familiar DNA sequences. These so called epigenetic modifications to the DNA, at precise locations, appear to be an important part of the physiological benefits of exercise.

"Our muscles are really plastic," says Juleen Zierath, Professor of Clinical Integrative Physiology in the Department of Molecular Medicine and Surgery. "We often say 'You are what you eat.' Well, muscle adapts to what you do. If you don't use it, you lose it and this is one of the mechanisms that allow that to happen."

The current study in Cell Metabolism shows that the DNA within skeletal muscle taken from people after a burst of exercise bears fewer methyl groups than it did before exercise. Those changes occur in stretches of DNA that serve as landing sites for different kinds of enzymes, called transcription factors, which in turn are involved in turning 'on' genes already known to be important in muscles' adaptation to exercise.

Juleen Zierath likens transcription factors to keys that unlock our genes. With those methyl groups firmly in place, transcription factor 'keys' are prevented from entering those DNA 'locks'. But when the methyl groups are removed it allows the keys to turn the locks, and boosts the capacity of muscle for work by producing new proteins that support sugar and fat metabolism.

"Exercise is already known to induce changes in muscle, including increased metabolism of sugar and fat," Zierath says, "Our discovery is that the methylation change comes first."

When the researchers made muscles contract in lab dishes, they saw a similar loss of methyl groups. Exposure of those muscles to caffeine had the same effect as well, as caffeine induces a release of calcium in a way that mimics the muscle contraction that comes with exercise. However, the researchers don't recommend that anyone should drink a cup of coffee in place of exercising, as it isn't clear that caffeine has all the other beneficial effects of exercise.

"Exercise is medicine, and it seems the means to alter our epigenomes for better health may be only a jog away," says Juleen Zierath.

Talking about the research environments in Europe and in the US, and in particular about her experience in Scandinavian countries, Juleen Zierath acknowledges that she is seen as the "American in Sweden." "After graduating in the US I was looking to do research in a laboratory which was active in the fields of human and clinical physiology. I looked at PhD programmes and published papers in this field, and many came from Scandinavian countries. I then decided to move to Europe" She added that "Europe is the place to be for me. It enables me to combine the molecular biology perspective I acquired in the US to directly work with clinicians to address questions relevant to improve patient care." She calls this approach "translational research" - taking research from the bench to the bedside.

When asked about the impact of the ERC grant on her research she explained that: "Most of the funding we have access to as researchers is limited, or it covers only a small part of what is actually needed to fully execute the project. In contrast, the ERC provides a substantial amount of funding. With a € 2.5 million grant running for five years, it goes without saying that such funding is sustained enough to enable the researcher to conduct risky projects." She added that she was really "honoured to be awarded an ERC grant. When you receive this kind of funding people are suddenly much more alert: both to your merits as a researcher and how critical it is that your work gets funded. Moreover, the ERC's funding schemes are reasonable to manage and there is really nothing bureaucratic about them."