7. Project Summary- Resource Core 2 Cardiovascular deconditioning, chronic inflammation, and endocrine-metabolic dysfunction are inherent to the pathophysiology of the physical impairments in older persons hindered by disabling chronic diseases of aging. Sarcopenia, poor fitness, inflammation, and acute events causing disability -- such as falls, stroke, and hip fracture -- occur with advancing age and may worsen mobility and increase risk for cardiovascular disease (CVD) and metabolic abnormalities. The Applied Physiology and Tissue Mechanisms Resource Core’s (RC-2) hypothesis is that exercise and activity-based rehabilitation can improve multiple physiological systems in older, mobility-limited individuals, leading to improved functional performance, reduced cardiometabolic disease risk, and prevention of functional decline. This core focuses on the following specific aims: 1)To facilitate the conduct of musculoskeletal and tissue mechanistic exercise rehabilitation and preventive biomedical research in aging and disability across the UM-OAIC pilot projects, UM-OAIC scholars’ research, Development Projects (DPs), and external NIH and VA funded research; and 2)To provide research support, mentoring, and training to UM-OAIC scholars, junior faculty, and UM-OAIC researchers in the performance of aging research relevant to exercise and rehabilitation-based restoration of function and the prevention of functional declines in older people with chronic disabling diseases. RC-2 leadership and investigators represent a multidisciplinary team of basic scientists with clinical geriatricians who have worked together for 15-20 years. The characterization of the clinical and metabolic phenotype(s) of individuals with stroke, hip fracture, and other chronic disabling diseases in RC-2 have allowed UM-OAIC investigators to develop successful specific exercise rehabilitation strategies to improve functional and clinical outcomes. Thus this core, in collaboration with the other UM-OAIC cores, will continue to support innovative research studies examining the mechanisms and physiological effects of multisystem rehabilitation and preventive strategies on functional and physiological outcomes in older adults aging with chronic disabilities, with translation of these outcomes in novel clinical trials.