AGING AND SKELETAL MUSCLE TISSUE GAS EXCHANGE

虽然肌肉减少（肌肉减少症）是众所周知的老年变化，但衰老对肌肉微血管的影响在很大程度上是未知的。关于肌肉毛细血管化随年龄增长而变化的数据一直是相互矛盾的，并且对老年肌肉中毛细血管纤维结构与纤维类型、大小和代谢特征的关系知之甚少。肌肉结构能力中氧气通量的新概念尚未被探索与衰老的关系，对于老年肌肉提取和利用氧气的能力的主要决定因素和限制因素也没有达成共识。利用我们开发的方法来评估肌肉毛细血管-纤维形态计量学的几个方面，我们确定了毛细血管-纤维界面的大小是有氧肌肉中氧气传输能力的关键，我们研究了其可塑性与纤维线粒体体积的关系，以应对增加的使用和长期缺氧。我们建议使用这些方法来检测衰老过程中肌肉对氧通量的能力，并研究其极限（）和可塑性与纤维需求和分布的关系。我们的具体目标是1)评估覆盖广泛纤维类型分布的老年肌肉从毛细血管到纤维线粒体的O2通量的结构能力，2)与热量限制动物进行比较，3)与废弃动物进行比较，4)评估长期增加使用的可塑性，5)测量线粒体呼吸速率，6)检查单个毛细血管的肌肉O2输送，7)模拟老年肌肉的氧合。我们的中心假设是，维持老年肌肉中从毛细血管到纤维线粒体的氧通量速率取决于维持毛细血管-纤维界面相对于纤维线粒体嵴表面积的大小，而与扩散距离、纤维类型分布或有氧能力水平无关。这些数据应该为理解衰老过程中血液组织氧转移肌肉能力的结构-功能相关性的关键方面提供新的见解，并且它应该有助于理解和管理老年人组织氧合受损。与理查森博士也参与衰老研究相反，本提案使用动物模型（大鼠和仓鼠）。

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).