The role of satellite cells in aged-skeletal muscle maintenance and hypertrophy

Sarcopenia, age-associated loss of muscle mass, causes decrements in muscle strength and function that negatively impact quality of life and limit independence in our growing aging population. Impairment and loss of the muscle stem cell, satellite cell, have been proposed to contribute to sarcopenia. We propose to utilize a novel genetic approach to directly test the necessity of satellite cells in aging muscle for the first time. This genetic strategy utilizes two established mouse strains that combine the specificity of satellite cells (Pax7CreER) and the effectiveness to ablate (Rosa26DTA) them in skeletal muscle across the lifespan. Moreover, mechanical overload induces a countermeasure to sarcopenia promoting muscle hypertrophy in aged animals. In both rodents and humans, evidence suggests that myofiber hypertrophy is attenuated with age, but the role satellite cells play in the muscle response to hypertrophic stimuli during aging remains unknown. The goals of this proposed project are to test directly the role of satellite cells in a) maintenance of muscle across the adult lifespan and b) response to a muscle hypertrophic stimulus. Understanding the roles of satellite cells in aged-skeletal muscle will directly impact future research focused on developing therapies and strategies to prevent age-associated muscle loss.