Vascular Structure and Function in Aged Skeletal Muscle

描述(申请人提供)：体能和肌肉功能随着年龄的增长而降低。与年龄相关的肌肉血流量减少及其在骨骼肌内部和之间的血管内分布被认为与老年人肌肉功能障碍有机械联系。这得到了以下观察的支持：随着年龄的增长，肺气体交换动力减慢，现在人们认识到，这些变化是由肌肉氧交换受损所驱动的，并导致收缩肌肉内代谢紊乱的增加，从而限制了运动耐量。然而，到目前为止，年轻和老年骨骼肌之间的关键结构和功能关系仍然不清楚。德尔普博士的实验室已经汇集了一种独特的组合，既有成熟的技术，也有最先进的技术来解决这个问题。我计划测试一个广泛的假设，即衰老会导致微循环功能障碍，从而损害氧气运输。这项工作将利用衰老的大鼠模型，这是一种被广泛接受的与人类状况类似的模型，其主要优势是允许进行非常侵入性的研究。开发有效的策略来减轻衰老对体能的有害影响取决于该人群肌肉功能障碍的机制基础的解决。

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.