Project Summary: RC-2 Age-related functional decline is accelerated by acute events by disabling conditions (e.g., stroke, hip fracture, arthritis, peripheral arterial disease) and chronic disease (e.g., cardiovascular disease, diabetes). These conditions predispose a multi-system decline that severely reduces functional independence and quality of life. The overarching goal of the UM-OAIC is to accelerate the development of meaningful interventions to improve disability related functional declines in older individuals. Evidence from studies by UM-OAIC investigators and others has linked the benefits of exercise to a reduction in the inflammation and endocrine- metabolic dysfunction that accompany disabling conditions in the older adults. These works inform our overarching hypothesis that exercise, activity-based, and multi-modal rehabilitation can improve multiple physiological systems in older mobility-limited individuals which in turn can improve functional performance, reduce cardiometabolic disease risk, and prevent functional decline. In this renewal, the RC-2 expands its clinical outcome measures and extends its support to parallel outcome measures in pre-clinical rodent models. RC-2 will be led by a multi-disciplinary team made up of Drs. Ryan, Katzel and Ward. Specific Aim 1 is to advance research focused on the mechanisms of functional decline in older persons with disability and the mitigation of decline with exercise or activity-based or multi-modal rehabilitation strategies. Specific Aim 2 is to provide mentoring and training to REC Scholars, affiliated 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. Through RC-2’s support of REC Scholars, pilot projects, development projects, and external projects, we will advance the UM-OAIC mission to reduce disability and restore function in older individuals with disabling conditions and translate our discoveries toward impactful evidence-based interventions.