Integrated Study of Musculoskeletal Loss and Restoration

Specific Aim 1: Investigate whether advancing age decreases the capacity to recover from a loss in musculoskeletal integrity induced by HS. Hypothesis: Restoration of musculoskeletal integrity is impaired with advancing age. Specific Aim 2: Determine whether the function of precursor cells and/or apoptotic mechanisms in bone and muscle are changed with aging in response to HS and reambulation. Hypothesis: Aging decreases the responsiveness ofmusculoskeletal precursor cells to changes in mechanical load. Specific Aim 3: Determine the effects of HS and reloading on myoblast and bone marrow stem cell function in vitro, using cells isolated from muscles and bone marrow of animals of different ages. Hypothesis: Aging alters in vitro proliferation, differentiation, and life span ofmusculoskeletal precursor cells from HS animals. Specific Aim 4: Investigate whether changes in the insulin-like growth factor 1 (IGF-1) pathway in the musculoskeletal system are involved in the decreased capacity to recover from disuse. Hypothesis: IGF-1 expression, signaling and/or responsiveness is altered in bone and muscle with aging under different loading conditions, influencing recovery from disuse.