Grant: Operating Grant: Geroscience Demonstration Grants

One of the most significant changes associated with normal aging is a progressive loss of muscle mass and strength, a biological process called sarcopenia. Sarcopenia can lead to mobility impairment, falls, and physical frailty in the elderly, dramatically impairing the quality of life of afflicted individuals. With the rapid demographic change of the aging population, sarcopenia will soon rank as one of the major financial burdens that our health care system will have to face. There is currently a lack of effective therapies to either prevent or treat sarcopenia, due in large part to the fact that its molecular and cellular bases are poorly understood. In the present research, we will test, directly in humans, the hypothesis that mitochondria, tiny structures essential for the muscle cell functioning, become dysfunctional with aging and that this accumulation of mitochondrial dysfunction results in a deterioration of the integrity of neuromuscular junction (the interface between neurones and muscle cells) and a decline in muscle mass and performance. We will also assess how physical activity protects against these aging-related changes affecting mitochondria and the NMJ. Finally, we will assess the robustness of recently identified biomarkers of sarcopenia. To ensure success, we have assembled a team of experts in mitochondrial biology (G Gouspillou), neurophysiology and the NMJ (R Robitaille & M Bélanger) as well as in Geriatrics and Gerontology (JA Morais, M Aubertin-Leheudre, & P Gaudreau). The results of the present research will provide important insights into the mechanisms underlying the aging-related deterioration of muscle function. In addition, they will enable us to better understand how physical activity exerts its protective impact against sarcopenia. This knowledge will be critical in developing novel strategies to prevent or even reverse sarcopenia and might provide medical professionals with robust biomarkers to identify patients at risk.