AGING AND SKELETAL MUSCLE TISSUE GAS EXCHANGE

衰老与骨骼肌组织气体交换

• 批准号: 6452644
• 负责人: ODILE A MATHIEU-COSTELLO
• 金额: $ 24.62万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6452644
• 关键词: aerobic exercise; age difference; aging; capillary; cellular respiration; hamsters; laboratory rat; microcirculation; mitochondria; morphometry; oxygen tension; oxygen transport; striated muscles

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).

尽管肌肉质量减少（肌肉减少症）是老年时的一种众所周知的变化，但衰老对肌肉微血管系统的影响却很大程度上未知。关于肌肉毛细血管化随衰老而变化的数据一直是矛盾的，并且人们对衰老肌肉中毛细血管纤维结构与纤维类型、大小和代谢特征之间的关系知之甚少。尚未探索与衰老相关的肌肉结构能力 O2 通量的新概念，并且对于高龄肌肉提取和利用 O2 能力的主要决定因素和限制尚未达成共识。使用我们开发的评估肌肉毛细血管-纤维形态测量的几个方面的方法，我们确定毛细血管-纤维界面的大小是有氧肌肉中 O2 传输能力的关键，并且我们检查了其与纤维线粒体体积的可塑性，以响应增加的使用和长期缺氧。我们建议使用这些方法来检查衰老过程中肌肉的 O2 通量能力，并研究其与纤维需求和分布相关的极限（）和可塑性。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 O2 通量的结构能力，涵盖广泛的纤维类型分布，2) 与热量限制的动物进行比较，3) 与废用进行比较，4) 评估长期增加使用的可塑性，5) 测量线粒体呼吸速率，6) 检查单个毛细血管中的肌肉 O2 输送，以及 7) 模型氧合 在老化的肌肉中。我们的中心假设是，老年肌肉中从毛细血管到纤维线粒体的 O2 通量速率的维持取决于毛细血管与纤维界面相对于纤维线粒体嵴表面积的大小的维持，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肌肉输送血液组织 O2 的能力的结构功能相关性的关键方面提供新的见解，并且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比，本提案使用动物模型（大鼠和仓鼠）。