Vascular Structure and Function in Aged Skeletal Muscle

描述（由申请人提供）：体能和肌肉功能随着年龄的增长而下降。骨骼肌内和骨骼肌之间的肌血流量及其血管内分布的减少与老年人的肌肉功能障碍有关。这得到了以下观察结果的支持：随着年龄的增长，肺部气体交换动力学减慢，现在认识到这些变化是由受损的肌肉氧交换驱动的，并导致收缩肌肉内代谢紊乱升高，从而限制运动耐量。然而，到目前为止，年轻和老年骨骼肌的关键结构和功能关系仍然不清楚。Delp博士的实验室已经组装了一个独特的组合，建立和国家的最先进的技术来解决这个问题。我计划测试一个宽泛的假设，即衰老会导致微循环功能障碍，从而损害氧气运输。这项工作将利用大鼠衰老模型，这是一种被广泛接受的人类状况模拟物，其主要优点是允许进行非常侵入性的研究。发展有效的策略，以减轻老化对身体能力的有害影响，是取决于在这个人群中的肌肉功能障碍的机制基础的决议。

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.