Grant: Operating Grant

Over the last 50 years, the proportion of the Canadian population over 65 y has nearly tripled, with a concomitant rise in the incidence of aging associated chronic diseases such as type 2 diabetes, cardiovascular disease, etc. Investigating mechanisms that may prevent chronic diseases and enhance the quality of life has become a public health priority. The foremost risk factor for many debilitating chronic diseases is lack of physical activity leading to obesity, poor fitness, and eventually skeletal muscle atrophy. A key player in the loss of muscle mass associated with inactivity is mitochondrial dysfunction. Mitochondria are cellular "powerhouses" that harness energy to sustain day-to-day activities. Low mitochondrial quality/content is strongly implicated in cancer, obesity, cardiovascular disease, and type 2 diabetes. Epidemiological studies have shown that endurance exercise training extends life expectancy, and reduces morbidity and physical disability; but the exact mechanism(s) are unclear. We have shown that the "conductor" in this process termed PGC-1a responds rapidly to endurance exercise and goes into both the nucleus and mitochondria of the cell, but we do not know what the initiating signals are for this coordinate induction. Animal studies have shown that elevation in PGC-1a content protects from muscle atrophy and mitochondrial dysfunction in old mice. Our proposed study will utilize endurance exercise in healthy mice together with antioxidant supplementation to provide an insight into the cellular signals that dictate PGC-1a mitochondrial localization and promote mitochondrial health. Understanding these mechanism(s) could lead to effective countermeasures for future interventions in diseased populations as targeted means of improving mitochondrial, and therefore muscle health.