Programme Contents

Developing epigenetic biomarkers - applications for exercise

Epigenetics describes the chemical modifications to DNA and its packaging proteins that modify gene expression and perpetuated through cell division. Examples of specific epigenetic modifications include DNA methylation, covalent histone modification and noncoding RNA.

Coordinated changes in epigenetic state drive the cellular specification that accompanies mammalian development, from the early embryo to old age. However, epigenetic state is, to a large extent, plastic and can be influenced by environmental factors, particularly during early development. Such changes can be ‘remembered’ as cells convert transient changes in gene expression to epigenetic changes that can perpetuate over many cycles of cell division. One of the earliest and well known pieces of evidence for this phenomenon came from a study that showed that DNA methylation changes in the growth factor gene IGF2 induces by the Dutch Famine at the end of the Second World War persisted for over sixty years (Heijmans et al., 2008). Therefore, it is not surprising that long-lasting epigenetic changes have been observed in skeletal muscle in response to exercise throughout the life course (Grazioli et al., 2017; Fernandes, Arida & Gomez-Pinilla, 2017; Howlett & McGee, 2017). Such changes are likely to regulate specific metabolic pathways. Furthermore, muscle stem cells isolated from individuals with varying levels of physical activity maintain their differential epigenetic state ex vivo (Sharples, Stewart CE & Seaborne, 2016).

An active area of research has been to study epigenetic responses to exercise interventions aimed at reducing the risk of chronic diseases such as type 2 diabetes. One such study found exercise-induced epigenetic and changes in the glucose transporter GLUT4 which were accompanied by changes to gene expression (Dos Santos et al., 2015). This shows that exercise-induced epigenetic changes can have direct effects on the metabolic state could potentially protect against type 2 diabetes.

What remains unknown is the extent to which the intensity and duration of physical exercise can drive epigenetic changes in genes associated with risk for cardiometabolic and other age-related diseases. Longitudinal clinical trials of exercise interventions that involve measurement of physiological and epigenetic changes in muscle cells will be necessary to address these questions.

Dos Santos JM, Moreli ML, Tewari S, Benite-Ribeiro SA. (2015). The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective. Metabolism 64(12), 1619-28.

Fernandes J, Arida RM, Gomez-Pinilla F. (2017). Physical exercise as an epigenetic modulator of brain plasticity and cognition. Neurosci Biobehav Rev 80, 443-56.

Grazioli E, Dimauro I, Mercatelli N, Wang G, Pitsiladis Y, Di Luigi L, Caporossi D. (2017). Physical activity in the prevention of human diseases: role of epigenetic modifications. BMC Genomics 18(Suppl 8): 802.

Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 105(44), 17046-9.

Howlett KF, McGee SL. (2016). Epigenetic regulation of skeletal muscle metabolism. Clin Sci (Lond) 130(13), 1051-63.

Sharples AP, Stewart CE, Seaborne RA. (2016). Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise. Aging Cell 15(4), 603-16.