Oxygen transport and utilization: Effects of age

氧气输送和利用：年龄的影响

• 批准号: 6589832
• 负责人: RUSSELL S RICHARDSON
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6589832
• 关键词: age difference; aging; cellular respiration; clinical research; dogs; exercise; human subject; intracellular transport; morphometry; muscle metabolism; nuclear magnetic resonance spectroscopy; oxygen tension; oxygen transport; perfusion

The general objective of Project 3 is to elucidate the mechanisms that govern the transport and utilization of O2 (VO2) by skeletal muscle and determine how these mechanisms are influenced by the aging process. Although a decreased muscle mass and reduced muscle respiratory capacity have been implicated in the age-related decrement in exercise performance, the role and importance of alterations in the O2 transport system may be of significance. O2 supply is essential for respiration and O2 availability modulates metabolism. Consequently, studies are proposed that examine skeletal muscle blood flow and metabolism across the spectrum of age in humans. A repeated measures design including arterial and venous blood samples and blood flow measurements during cycle and isolated knee-extensor exercise will provide unique insight into the effect of age on the delivery and uptake of O2 by varying the importance of central and peripheral limitations. Muscle morphometry, again on the same subjects, will afford the opportunity to link structure with function in an effort to better understand the age-related decline in metabolic capacity. As intracellular P02 is key to understanding how O2 delivery translates into effects on metabolism, will continue to utilize 1H magnetic resonance spectroscopy (MRS) of myoglobin to evaluate variations in this final step of the O2 cascade from air to tissue. Finally, a complete understanding of O2 supply and demand is impossible without a method to assess the illusive phenomenon of perfusion/V02 matching. We present exciting preliminary data which combine MR perfusion imaging and 31P chemical shift imaging to provide this information in vivo. This novel technique will initially be used to assess the influence of age and O2 availability on perfusion/V02 matching, and may ultimately produce a clinically applicable tool to assess skeletal mu7scle dysfunction. Within these broad goals we will combined animal studies theoretical analyses, biochemistry, and the study of molecular mechanisms to better understand O2 transport and utilization with aging.

项目3的总体目标是阐明支配骨骼肌运输和利用O2(VO2)的机制，并确定这些机制如何受到衰老过程的影响。虽然肌肉质量下降和肌肉呼吸能力下降与年龄相关的运动能力下降有关，但O2运输系统的变化可能具有重要意义。氧气供应对呼吸是必不可少的，氧气供应调节新陈代谢。因此，有人建议进行研究，检查人类不同年龄段的骨骼肌血流和代谢。重复测量设计，包括循环和单独的伸膝运动中的动脉和静脉血样和血流量测量，将通过改变中枢和外周限制的重要性，提供对年龄对氧气输送和摄取的影响的独特见解。肌肉形态测量，同样是在相同的主题上，将提供将结构与功能联系起来的机会，以努力更好地理解与年龄相关的代谢能力下降。由于细胞内P02是了解O2传递如何转化为对新陈代谢的影响的关键，因此我们将继续利用肌红蛋白的1H磁共振波谱(MRS)来评估O2从空气到组织的这最后一步的变化。最后，如果没有一种方法来评估灌流/V02匹配的错觉现象，就不可能完全了解氧气的供需情况。我们提供了令人兴奋的初步数据，结合了MR灌注成像和31P化学位移成像来提供体内的这一信息。这项新技术最初将用于评估年龄和氧气供应对血流/V02匹配的影响，并最终可能产生一种临床适用的工具来评估骨骼肌功能障碍。在这些宏大的目标中，我们将结合动物研究、理论分析、生物化学和分子机制研究，以更好地了解氧气随年龄增长的运输和利用。