MUSCLE DISUSE AND CONTRACTILE DYSFUNCTION IN THE ELDERLY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Skeletal muscle disuse is an important contributing factor to disability in the elderly. Elderly individuals are more likely to experience disuse and are more susceptible to its debilitating effects because of their diminished physiological reserve. Despite these facts, the cellular and molecular mechanisms whereby disuse promotes skeletal muscle contractile dysfunction in this population remain largely unstudied. In a recent grant application to NIH, we proposed to systematically test for modifications of skeletal muscle fiber structure and function that underlie disuse-related contractile dysfunction in elderly humans by studying patients with end-stage, bilateral osteoarthritis. Specifically, we will compare data from these patients to healthy elderly controls with normal activity levels. We hypothesize that muscle disuse in the elderly impairs single muscle fiber contractile function through alterations in acto-myosin cross-bridge kinetics, myofilament protein content and the mechanical properties of the myofilament lattice. In the grant application, we propose to assess patients for leg muscle strength (dynamometry), total and regional body composition (radiologic imaging techniques: dual-energy x-ray absorptiometry and CT), physical activity levels (accelerometer) and obtain tissue from the thigh muscle (vastus lateralis) via percutaneous biopsy. In this submission, we are requesting permission to study 4 patients with osteoarthritis in order to obtain preliminary data for the grant submission. This data can be sent to NIH up to 2 wks prior to the review of the application. This will be important data to demonstrate our ability to recruit and test osteoarthritis patients and could provide data to support our hypotheses regarding the effects of disuse on muscle contractile function. In these 4 patients, we will perform assessments of muscle strength (dynamometry), body composition (dual-energy x-ray absorptiometry), physical activity (accelerometery for 1 wk) and obtain tissue via muscle biopsy.