The proposed study is submitted in response to the Program Announcement FRAILTY IN OLD AGE: PATHOPHYSIOLOGY AND INTERVENTIONS (PAS-03-122). Frailty is a heterogeneous syndrome whose features include impaired strength and body composition, gait and fatigue. Most information on frailty comes from studies limited to persons with clinical measures. Since impaired motor function is a prominent characteristic of many of the key features of frailty, we hypothesize that degenerative changes in spinal motor neurons, which directly control motor function, contributes to the development of frailty. It is further hypothesized that since physical activity and the growth factor IGF-I are thought to affect the integrity of spinal motor neurons, that their association with frailty is mediated through degeneration of spinal motor neurons. The proposed study will capitalize on a unique cohort of about 900 older persons from the Rush Memory and Aging Project (R01 AG17917), who have agreed to annual detailed clinical evaluation and donation of spinal cord after death. Identifying the structural basis of frailty could offer an empirical approach to exploring the pathologic indices linking risk factors to the development of frailty, and provide a conceptual basis for the development and testing of interventions to reduce the burden of this common syndrome on our aging population.
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