Vascular Structure and Function with Aging

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DESCRIPTION (provided by applicant): Physical capacity and muscular function are reduced with aging. Age-associated reduction in muscle blood flow and its intravascular distribution within and between skeletal muscles is thought to be linked mechanistically to muscle dysfunction in older individuals. This is supported by the observation that pulmonary gas exchange dynamics are slowed with advancing age and it is now recognized that these changes are driven by impaired muscle oxygen exchange and result in elevated metabolic perturbations within contracting muscle that limit exercise tolerance. To date, however, key structural and functional relationships within young and aged skeletal muscle remain obscure. Dr. Delp's lab has assembled a unique combination of established and state-of-the art techniques to address this problem. I plan to test the broad hypothesis that aging induces microcirculatory dysfunction that impairs oxygen transport. This work will utilize the rat model of aging, a widely accepted analog of the human condition that has the major advantage of permitting very invasive studies. Development of effective strategies to attenuate the deleterious effects of aging on physical capacity is contingent upon resolution of the mechanistic bases for muscle dysfunction in this population.