AGING AND SKELETAL MUSCLE TISSUE GAS EXCHANGE

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Whereas decrease in muscle mass (sarcopenia) is a well known alteration in old age, the effect of aging on the muscle microvasculature is largely unknown. Data on changes in muscle cappilarization with aging have been contradictory, and little is known to capillary-fiber structure in relation to fiber type, size and metabolic characteristics in aged muscles. New concepts in muscle structural capacity for O2 flux have not been explored in relation to aging and there is no consensus on the major determinant(s) and limitation(s) to muscle capacity to extract and utilize O2 in advanced aged. Using methods we developed to assess several aspects of muscle capillary-fiber morphometrics, we established that the size of the capillary-to-fiber interface is key to O2 transfer capacity in aerobic muscles, and we examined its plasticity in relation to fiber mitochondrial volume in response to increased use and chronic exposure to hypoxia. We propose to use these methods to examine muscle capacity for O2 flux in aging, and study its limit() and plasticity in relation to fiber demand and distribution. Our specific aims are 1) to assess the structural capacity for O2 flux from capillary to fiber mitochondria in aged muscles covering a wide range of fiber type distributions, 2) compare with calorically-restricted animals, 3) compare with disuse, 4) assess plasticities with chronically increased used, 5) measure mitochondrial respiratory rates, 6) examine muscle O2 delivery in individual capillaries, and 7) model oxygenation in aged muscles. Our central hypothesis is that maintenance of O2 flux rates from capillary to fiber mitochondria in aged muscles depends on the maintenance of the size of the capillary-to-fiber interface relative to the to the surface area of fiber mitochondrial cristae, independent of diffusion distance, fiber type distribution or level of aerobic capacity. The data should provide new insights in the understanding of key aspects of structure-function correlations in muscle capacity for blood-tissue O2 transfer during the aging process, and it should help in the understanding and management of impaired tissue oxygenation in the elderly. In contrast of Dr. Richardson also involving in aging studies, the present proposal uses animal models (rat and hamster).