Mitochondria and Muscle within the HEALTH Study
Funded Grant
Overview
Affiliation
View All
Overview
description
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.
