Mechanisms of human skeletal muscle remodelling with exercise

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Skeletal muscle is an incredibly plastic tissue resulting from its remarkable ability to break down old and/or damaged proteins and make (synthesize) new functional ones. These processes occur simultaneously and continuously, are enhanced in response to exercise and nutrition, and ultimately function to `remodel' this important tissue. The synthesis of new muscle proteins (MPS) significantly determines whether a muscle gets bigger and stronger, such as with resistance exercise (REX) through the synthesis of force-generating myofibrillar (MYO) proteins, and/or develop a greater endurance capacity, such as with endurance exercise (END) through the synthesis of energy-producing mitochondrial (MITO) proteins.****    The synthesis of some muscle proteins can be enhanced with the ingestion of dietary amino acids (AA) - the building blocks of protein. However, most research focuses on the response immediately after REX without consideration for the effects of END and/or time points later (e.g. 24h) in the muscle remodelling process. Therefore, this research program will take a unique "mouth-to-muscle" approach to studying how dietary AA can support human skeletal muscle remodelling at various times after exercise through stable isotopes (AA "tracers" that are heavier than normal) and the use of specialized "intrinsically-labelled proteins". These novel proteins contain "tracers" that will allow us to measure how their AA are delivered to and subsequently taken up by the muscle to be used for the synthesis of new MYO and MITO proteins after different types of exercise. To advance our understanding of how dietary AA can enhance exercise-induced muscle remodelling, we will also measure the presence and location of specific proteins in human muscle that are involved in transporting AA into the cell and regulating how they are used to build new muscle.****    Exercise also activates satellite cells (SC). Although these muscle stem cells help repair damaged and/or support growing or remodelling muscle fibres, their activity is primarily investigated in response to REX only and rarely co-incident with changes in MPS. Therefore, we will also utilize novel "tracers" combined with SC-specific methods to systematically assess the co-regulation and/or potential synergy between changes in MPS and SC activation after both REX and END. This mulit-discipline approach will help bridge the gap between the traditional dichotomous MPS- and SC-centric views of muscle remodelling.****    Collectively, information generated from this research program will provide a more holistic insight into the plasticity of human muscle and the mechanisms that regulate how it remodels in response to different types of exercise with a supporting role for nutrition. Ultimately, this knowledge will inform the most effective nutraceutical, therapeutic, and pharmacological approaches to maintain and enhance muscle mass and quality in humans.***