Mitochondria and Muscle within the HEALTH Study

项目总结/摘要 该提案利用我们正在进行的NIH资助的随机临床试验（R 01 AG 066562）来回答关键问题， 关于运动对老年艾滋病毒感染者的机械作用的时间敏感问题，以回应非- AG-23-008在美国，大多数艾滋病毒感染者（PWH）现在年龄在50岁或以上， 与未感染艾滋病毒的人相比，身体机能的下降速度加快。运动是一种 预防或逆转身体功能障碍的最有效干预措施。我们最近完成了一个 24-中强度或高强度心血管运动和抗阻运动随机干预一周， 年龄≥50岁的成年人，有和没有艾滋病毒。有和没有艾滋病毒的参与者都经历了10-45%的改善 在功能测量中，随机分配到高强度运动组的人有更大的改善。 尽管功能改善的百分比相似，但线粒体含量的几个关键指标 威尔斯亲王医院病人的运动量没有增加或减少。对适应环境至关重要的机制 PWH未知。在健康研究（R 01 AG 066562）中，我们入组了100名年龄≥50岁的PWH， 16周高强度间歇训练（HIIT）与持续中等强度运动的影响 (CME)抗阻运动对身体机能和骨骼肌线粒体氧化能力的影响， 通过奥罗博罗斯和线粒体含量测量。在这项建议的补充资金下，我们建议 利用现有的卫生基础设施和成果来描述HIIT与CME对 体内骨骼肌结构和功能。我们将测试这一总体假设：骨骼整合失败 肌肉、生物能量学、氧化通量和血流干扰了运动训练的适应性反应， PWH。我们将通过比较16周HIIT与CME对骨骼肌的影响来研究我们的假设。 线粒体功能和氧化通量（目的1），并确定血流动力学和 老年PWH运动适应的代谢机制（目的2）。这些调查结果将确定目标， 并且抵抗运动训练，特别是在经历高功能负担的个体中。 损伤未来的干预性试验可以针对增加治疗以改善氧化能力，或 最大化血流。通过利用HIIT与CME的母研究设计，我们将获得有关 HIIT对这些肌肉结果的额外益处（或危害），并提供对 PWH功能障碍的病因和对运动的适应。

Project Summary/Abstract This proposal leverages our ongoing, randomized NIH-funded clinical trial (R01 AG066562) to answer critical, time-sensitive questions on the mechanistic effects of exercise among older adults with HIV, in response to NOT- AG-23-008. The majority of people living with HIV (PWH) in the U.S. are now aged 50 or older and experience declines in physical function at an accelerated rate compared to people aging without HIV. Exercise is one of the most effective interventions to prevent or reverse physical function impairments. We recently completed a 24-week randomized intervention of moderate or high intensity cardiovascular and resistance exercise among adults aged ≥50 with and without HIV. Both participants with and without HIV experienced 10-45% improvements in functional measures, with greater improvements among those randomized to higher-intensity exercise. Despite similar if not greater percent improvement in function, several key measures of mitochondrial content failed to increase or decreased with exercise among PWH. The mechanisms essential to exercise adaptation in PWH are unknown. In the HEALTH Study (R01 AG066562), we are enrolling 100 PWH aged ≥50 to compare the impact of 16 weeks of high-intensity interval training (HIIT) versus continuous moderate intensity exercise (CME) and resistance exercise on physical function and skeletal muscle mitochondrial oxidative capacity, as measured by Oroboros and mitochondrial content. With the supplemental funding of this proposal, we propose to leverage the existing HEALTH infrastructure and outcomes to characterize the impact of HIIT vs CME on in vivo skeletal muscle structure and function. We will test this overarching hypothesis: Failed integration of skeletal muscle, bioenergetics, oxidative flux and blood flow interfere with the adaptive response to exercise training in PWH. We will investigate our hypothesis by comparing the effect of 16 weeks of HIIT vs CME on skeletal muscle mitochondrial function and oxidative flux (Aim 1), and determining the relative contributions of hemodynamic and metabolic mechanisms to exercise adaptations in older PWH (Aim 2). These findings will identify targets responsive and resistant to exercise training, particularly among individuals who experience a high burden of functional impairments. Future interventional trials can target the addition of a therapy to improve oxidative capacity, or maximize blood flow. By leveraging the parent study design of HIIT vs CME, we will gain valuable insights into the added benefit (or harm) of HIIT on these muscle outcomes and provide a comprehensive understanding of the etiology of functional impairments in PWH and adaptions to exercise.