Identical twin study provides a molecular link between MVPA and metabolic disease – prof. phil jakeman

The study of identical (or monozygotic, MZ) twins is a powerful tool to advance our understanding of how physical activity impacts on metabolic diseases such as obesity and diabetes.

Since identical twins have the same genetics, disease risk is influenced by how people interact with their environment and not just the genes they inherited. This is termed epigenetics. Epigenetics has a critical role in the regulation of gene expression and describes the molecular modifications on DNA that can regulate gene activity that are independent of DNA sequence. In contrast to genetics, environmental exposures can directly regulate epigenetic processes to impact gene expression, cell and developmental biology, and the physiology of the organism.

Regular exercise, or physical activity (PA), is a common, environmental, health behaviour that can induce epigenetic changes and, hence, disease susceptibility. Yet, current evidence suggests that not all will respond or adapt in a similar manner to physical activity. The study of epigenetic modification in gene expression provides a tool to investigate the responder/non-responder paradigm. Recently published in Nature’s Scientific Reports1, an epigenome-wide association study (EWAS) was performed on monozygotic-twins (MZ) reared together as children, but who live apart as adults. Objectively measured physical activity (PA) levels of twin pairs with discordant levels of the physical activity were studied to investigate associations between PA levels, including neighbourhood walkability, and epigenetic alterations that impact metabolic risk. Combined observations demonstrated behaviours such as physical activity appear to promote systemic epigenetic alterations that impact metabolic risk. Physical activity discordance was defined as one twin having at least 150 min of moderate to vigorous physical activity (MVPA) per week, and their co-twin having less than 150 min MVPA. The twin in the discordant pair with a higher level of physical activity had epigenetic alterations that correlated with reduced body mass index and waist circumference and was associated with fifty genes identified as specific to vigorous physical activity and metabolic risk. The findings provide a molecular mechanism for the link between physical activity and metabolic disease. Importantly, research on this topic and correlations with specific molecular and physiological parameters will elucidate how epigenetic adaptations can mediate, at a molecular level, how PA reduces pathologies associated with obesity and associated metabolic disease.

The PESS Department’s research base is well positioned to contribute to an understanding of the epigenetic adaptation to physical activity. There is a strong body of work defining the level of PA in selected populations and external research funding to faculty within PESS supports laboratory facilities and expertise to study the molecular biology of exercise and engage further in the epigenetics of adaptation to physical activity.

1.       Duncan, G.E., Avery, A., Thorson, J.L.M. et al. Epigenome-wide association study of physical activity and physiological parameters in discordant monozygotic twins. Sci Rep 12, 20166 (2022). https://doi.org/10.1038/s41598-022-24642-3

 

Professor Phil Jakeman PhD FTPS, is a Professor of Sport and Exercise Sciences, in the Department of Physical Education and Sport Sciences in the University of Limerick. Research focus is the study of human physiology and biochemistry of exercise investigating changes in the human phenotype in response to exercise and exercise x nutrient interaction. Translational work relates to neuromuscular disease, osteoporosis, insulin resistance, obesity and age-related sarcopenia.

Contact: Phil.Jakeman@ul.ie  ORCID

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