Increasing clinical and experimental data provide evidence that aging and physical frailty are strongly linked to fundamental mechanisms of inflammation. The fundamental hypothesis of RC-4 is that common biological mechanisms in aging may be accelerated in selected disability conditions, such as stroke and hip fracture. The mission of RC-4 is to investigate biologic mechanisms that underlie the disability of advancing age at the tissue, cellular, molecular, and genetic level with a focus on muscle, adipocytes, and endothelial cells. RC-4 will provide consultative expertise, technical support and training, and access to services and resources for the conduct of muscle, adipocyte, and vascular biology research in disabled older people. RC-4 will a) investigate inflammatory-oxidative injury markers are the tissue, cellular and genetic level in muscle, adipose tissue and vascular endothelial cells;b) compare the similarities and differences between aging and select disability conditions in terms of sarcopenia, altered muscle structure/function, insulin resistance, and the genetic underpinnings of accelerated atherosclerosis, and c) determine the effects of targeted exercise programs on structural, inflammatory and metabolic abnormalities of muscle, adipose tissue, thrombosis and hemostasis, and vascular endothelium in these disabled populations. RC-4 will collaborate with RC-1 in the design of collaborative translational bench research studies, with RC-2 for measures of muscle performance to understand the clinical relevance of muscle structural and functional abnormalities, with RC-3 to relate abnormalities in body composition and glucose metabolism with changes at the level of muscle and adipose tissue, and with RC-3 to relate systemic measures of inflammation and abnormal metabolism to defects in vasomotor reactivity with abnormalities of thrombosis and markers of endothelial cell injury, and finally with RC-5 to explore statistical relationships of the RC-4 data at the level of tissue, cell, and gene in relation to measures from the other Cores. RC-4 will facilitate Intra- and Inter-Pepper collaborative research. With a better understanding of these structural, molecular, and metabolic muscle abnormalities and their response to exercise, we can optimize exercise interventions that improve muscle structure and functional outcomes, metabolic function, cardiovascular disease risk profile, and consequent risk of arteriosclerosis and thrombosis in these chronic disability conditions.