AGING AND SKELETAL MUSCLE TISSUE GAS EXCHANGE

虽然肌肉质量的减少(骨质疏松症)是众所周知的老年变化，但衰老对肌肉微血管系统的影响在很大程度上是未知的。随着年龄的增长，肌肉头状化的变化的数据一直是相互矛盾的，对于毛细血管纤维结构与纤维类型、大小和老年肌肉的代谢特征之间的关系知之甚少。与衰老相关的肌肉结构氧通量能力的新概念尚未被探索，对于高龄肌肉氧摄取和利用能力的主要决定因素(S)和限制(S)也没有达成共识。使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转移能力的关键，并检测了它的可塑性与纤维线粒体体积的关系，以响应增加使用和长期暴露于低氧。我们建议使用这些方法来检测肌肉在衰老过程中对O2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)评估老年肌肉中从毛细血管到纤维线粒体的氧通量的结构能力，包括广泛的纤维类型分布，2)与热量限制动物的比较，3)与废用动物的比较，4)评估长期增加使用的可塑性，5)测量线粒体呼吸速率，6)检查单个毛细血管中肌肉的氧气输送，以及7)老年肌肉的氧合模式。我们的中心假设是，在衰老的肌肉中，维持从毛细血管到纤维线粒体的氧通量速率取决于毛细血管到纤维界面相对于纤维线粒体脊表面积的大小的维持，而与扩散距离、纤维类型分布或有氧能力的水平无关。这些数据将为理解衰老过程中肌肉对血液-组织氧转移能力的结构-功能相关性的关键方面提供新的见解，并有助于理解和处理老年人组织氧合受损的问题。与理查森博士也参与衰老研究不同，本提案使用了动物模型(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).