Skeletal muscle regeration during aging and physical exercise : role of oxidative stress and myostatin

Prix de meilleur communication orale (Young Investigator Award)International audienceBackground : Skeletal muscle aging is characterized by impairments in regenerative processes that promote the decline of its mass, strengthand endurance (Le Grand and Rudnicki 2007). More than the intrinsic regenerative potential of satellite cells (SC), intracellular environment appears responsible to the age-related decrease of SC activity (Conboy, Conboy et al. 2005). This study was designed to study the involvement of myostatin and reactive oxygen species (ROS) on myogenic regulator factors (MRFs) expressions during aging processand in response to endurance training in skeletal muscle of young and aged rats. Methods : 22 young (5 months) and aged (22 months) male Wistar rats were exercised for 3 weeks following endurance training. The intensity of the training was set at 75% VO2max. Analyses were realized in gastrocnemius muscles. Gastrocnemius muscle was chosen because it is one of the most recruited muscles during the exercise training protocol and one of the most affected by sarcopenia due to a large proportion of type II fibers (Arora, Husom et al. 2008) Results : We observed that Myf-5, myoD and myogenin mRNA increased with age, without any change in protein content. mRNA of p21, an inhibitor of SC proliferation, was higher in aged skeletal muscle. Aging also increased oxidative damage (protein carbonylation, glutathione status), myostatin protein content and activated p38-mitogen-activated protein kinase. Endurance training reduces myostatin mRNA only in aged skeletal muscle, but did not change MRFs expression and oxidative stress status. Discussion : Myostatin and ROS could be key-elements of intracellular environment that impaired regenerative processes in aged skeletal muscle, by modulating MRFs and p21 expression. Further investigations using antioxydant treatments and myostatin inhibitors in aged animals are required to confirm this hypothesis. In addition, our results suggest that positive effects of endurance training on muscle mass and strength in aged population cannot be explained by changes in basal MRFs and p21 expression