Grant: Project Grant

Exercise is considered universally beneficial for the health of people who perform it regularly. A low amount (mass) of skeletal muscle with poor function gives rise to insulin resistance (type 2 diabetes) and is associated with excess morbidity and premature mortality. We have documented that major exercise outcomes, including insulin sensitivity and muscle mass, improve in less than 30% of exercise-trained people. We don't know why, but this is an important question to study since a lack of response to exercise shares many parallels with responsivity to drugs and other lifestyle interventions. Differences in the molecular (gene) responses to exercise training in skeletal muscle provide clues to exercise-induced drivers of exercise adaptations. We have created a large banked (stored in freezers) store of skeletal muscle that has allowed us to study molecular transducers of the benefits of exercise in >1,000 humans. This large database already exists and costs (Canadian, UK and US government funding) ~$20M to generate (over almost ~10 years). We have used this resource to generate methods and establish quality control procedures. We now wish to add new samples to answer why exercise is not universally beneficial to the same degree for everyone, AND what we might do to change this. While exercise is a practical and low-cost intervention for alleviating the risk of chronic disease and mitigating cellular aging, we need to understand how to 'personalize' its prescription. The proposed work aims to identify driver molecules, including genes and proteins, so that we can understand why people do not always benefit from exercise training and what we can do to address this. We will use genes and their products from more than >1000 individuals that we have obtained before and after closely supervised training. We also have two new unique cohorts of younger and older individuals, and we wish to collect more data from older persons.