Mechanosensory Signal Transduction in Aging Muscle

骨骼肌减少症是一种与年龄相关的骨骼肌质量减少和

Sarcopenia is an age associated reduction in skeletal muscle mass and may contribute to physical disability and loss of independence. It is hypothesized that the effects of sarcopenia could be delayed or largely prevented if existing musculature could be induced to hypertrophy. Although it is well accepted that muscle adaptability declines with aging, a fundamental issue remains unresolved: What is the molecular basis for the decreased ability of aged muscle to undergo adaptation? In cardiac tissue it is apparent that increased loading is able to mediate cellular hypertrophy. Whether a similar mechanism exists in skeletal muscle is not known. The overall goal of this study is to identify potential independent or shared intracellular signaling cascades through which increased muscle loading regulates gene expression in adult and aged skeletal muscle. To fulfill this goal, muscles from adult, middle aged, and aged or senescent Fisher 344 X Brown Norway (F1) rats will undergo stretch in vitro and activation will be determined. F12 hybrid rats were chosen because novel data from our laboratory has demonstrated that aged F1 animals are incapable of undergoing load induced muscle hypertrophy. The hypothesis for this project is that age associated decreases in muscle adaptation are related to a decrease in muscle mechanosensory signal transduction. The aims of this proposal are: Aim 1). To determine if stretch induced activation of MAPK family members is attenuated in aged muscle compared to adult muscle. Aim 2). To determine if the activity of FAK is increased by muscle stretch in adult and aged skeletal muscle. This work has broad application to basic and applied areas of the biomedical and health science fields. At the basic science level, these studies will increase our understanding of the pathways contractile tissues may use during the adaptation to altered loading conditions. At the more applied level, this research will provide will provide insight into the pathways regulating skeletal muscle hypertrophy, and to identify those pathways which could be targets for novel therapeutic strategies to prevent muscle wasting in patients and the frail elderly.