Title: Regulation of the Extracellular Matrix in Human Skeletal Muscle and the Influence of Resistance Exercise
Thesis Supervisor: Cameron Mitchell
Committee Members: Alex Scott, Michael Koehle, Fabio Rossi
Chair: Bill Sheel
Abstract: The extracellular matrix (ECM) of skeletal muscle is dynamic compartment that plays an important role in muscle health and function. Its primary component is collagen, and at rest, collagen turnover (breakdown and synthesis) is relatively stable, but in response to a stimulus like exercise, it increases. Intramuscular collagen accumulation occurs when there is an imbalance in synthesis and breakdown, favouring synthesis. It is implicated to negatively affect muscle function and has been demonstrated in models of ageing and knee osteoarthritis (OA). The cause of this accumulation is unknown; however, evidence suggests that it may be a factor of reduced breakdown, rather than increased synthesis. Therefore, the aim of this thesis is the understand if dysregulated collagen breakdown contributes to collagen accumulation. This thesis also aims to understand to what degree the natural ageing process causes intramuscular collagen accumulation, as compared to age-related comorbidities. Finally, this thesis will investigate the role of collagen breakdown in adaptation to resistance exercise in skeletal muscle.
To understand the degree to which the natural ageing process contributes to collagen accumulation, we will first complete a meta-analysis of the literature on intramuscular collagen accumulation in healthy young and older adults (Study 1). For Study 2, we will recruit healthy young and older adults and investigate if there are age-related differences in regulators of collagen breakdown after acute resistance exercise. For Study 3, we will recruit individuals with and without knee OA, as a more severe model of intramuscular collagen accumulation, and examine the same outcomes as Study 2. We will assess intramuscular collagen by histology, and we will measure regulators of collagen breakdown in the muscle by gene expression, protein content and protein activity analyses.
We hypothesize that older adults and individuals with knee OA will demonstrate intramuscular collagen accumulation relative to their comparative group. We also expect regulators of collagen breakdown to increase post-exercise in the healthy muscle, but for this response to be blunted when intramuscular collagen accumulation is present. The results of these studies will further our understanding of the ECM of skeletal muscle and its regulation after acute resistance exercise. It will offer insight into the molecular mechanisms of intramuscular collagen accumulation, as well as will help with understanding the degree to which the natural ageing process is a contributor, compared to age-related comorbidities like knee OA.