THE EFFECT OF ELECTRICAL STIMULATION ON AGED SKELETAL MUSCLE REGENERATIVE POTENTIAL

[摘要] Increasing age typically results in a decreased skeletal muscle regenerative capacity after injury, a decreased muscle mass and weakness, ultimately resulting in an increased likelihood for falls, susceptibility to recurrent injury, and a prolonged recovery. In response to injury, aged muscle displays a decreased capacity to regenerate damaged myofibers. Instead, the repair response is characterized by fibrotic accumulation, a response that has been attributed to dysfunction of the muscle stem cell (MuSC) population. MuSCs are a reserve cell population that plays a central role in dictating muscle regeneration. Muscle contractile activity, elicited by exercise or electrical stimulation, for example, has been suggested to be an important intervention to increase blood flow to the injury area and to promote the activation of muscle MuSCs. The purpose of this study is to test the hypothesis that neuromuscular electrical stimulation (Estim) inhibits activation of the muscle progenitor cell (MPC) fibrogenic molecular program to enhance skeletal muscle regeneration in aged animals. MPCs represent a heterogenous myogenic cell population, the majority of which are MuSCs. Our in vivo studies demonstrate that two weeks of Estim enhances myofiber regeneration and increases tetanic force recovery in aged muscles after an acute injury. In vitro, we find that improved muscle regeneration in aged muscle following the application of Estim is concomitant with a rejuvenated MPC phenotype. Our results further suggest that the beneficial effect of Estim on MPC regenerative potential may be mediated by up-regulation of the anti-aging protein, Klotho. Taken together, these data provide evidence that Estim is a safe and effective method and to improve functional recovery after an acute injury in aged muscle. It is anticipated that findings from this study will aid in the development of clinically relevant rehabilitation programs to enhance the muscle healing response in a geriatric population.

[发布机构] the University of Pittsburgh