AGING AND SKELETAL MUSCLE TISSUE GAS EXCHANGE

尽管肌肉质量减少（肌肉减少症）是老年人的一种众所周知的变化，但衰老对肌肉微血管系统的影响在很大程度上是未知的。关于肌肉毛细化随年龄变化的数据一直是矛盾的，并且对老年肌肉中与纤维类型、大小和代谢特征有关的毛细纤维结构知之甚少。尚未探索与衰老相关的肌肉结构能力中的新概念，并且对于晚期老年人肌肉提取和利用O2能力的主要决定因素和限制因素尚未达成共识。使用我们开发的方法来评估几个方面的肌肉毛细纤维形态计量学，我们建立了毛细纤维界面的大小是关键的有氧肌肉中的O2传输能力，我们研究了其可塑性与纤维线粒体体积的增加使用和慢性暴露于缺氧。我们建议使用这些方法来检查肌肉的能力，在老化过程中的O2流量，并研究其限制（）和可塑性与纤维的需求和分布。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中从毛细血管到纤维线粒体的O2通量的结构能力，2）与热量限制动物比较，3）与废用比较，4）评估长期增加使用的可塑性，5）测量线粒体呼吸率，6）检查个体毛细血管中的肌肉O2输送，和7）模拟老化肌肉中的氧合。我们的中心假设是，在老年肌肉中，从毛细血管到纤维线粒体的O2通量率的维持取决于毛细血管到纤维界面相对于纤维线粒体嵴的表面积的大小的维持，独立于扩散距离、纤维类型分布或有氧能力水平。这些数据应该提供新的见解，在衰老过程中的血液组织O2转移的肌肉能力的结构-功能相关性的关键方面的理解，它应该有助于在老年人受损的组织氧合的理解和管理。与Richardson博士也参与衰老研究相比，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).