Aging and Physical Functioning in HIV

描述（由申请人提供）：候选人是一名有前途的年轻研究者，拥有内科和传染病委员会认证，临床研究理学硕士学位，致力于以患者为导向的衰老和艾滋病毒研究。她的职业规划和研究计划与她的长期目标是一致的，她想成为一名独立的临床研究者，并在学术老年医学和艾滋病方面发挥领导作用。在美国，老年人在感染艾滋病毒的成年人中所占的比例越来越大。有氧能力降低、线粒体氧化功能障碍和瘦肌肉量减少是影响艾滋病毒感染和未感染的老年人的问题。然而，在感染艾滋病毒的情况下，肌肉减少症和氧化功能障碍可能更为明显，抗逆转录病毒治疗的代谢作用进一步加剧了这种缺陷。了解老年艾滋病毒感染者功能受限的潜在机制将使我们能够设计有效的预防和治疗策略，以改善和保持这一快速增长的老年患者群体的功能。本研究的目的是研究衰老影响HIV成人身体功能和有氧能力的机制（AIM 1），并确定有氧运动训练是否能改善老年HIV成人的功能和心血管表现（AIM 2）。假设# 1。随着年龄的增长，身体功能的降低将受到艾滋病毒成人基线免疫状态的影响，并且同样会受到艾滋病毒感染与阴性成人的医疗合并症的影响。假设2。骨骼肌氧化功能障碍是与老年HIV成人有氧能力降低和功能限制相关的中心因素。假设# 3。与久坐不动的老年HIV对照组相比，有氧运动训练将改善老年HIV受试者的肌肉氧化功能障碍，以及相关的功能限制和有氧能力降低；然而，改善可能受到肌肉减少症和hiv相关肌病程度的限制。拟议的研究将为后续研究奠定基础，这些研究将调查基于运动的最佳康复策略和改善老年艾滋病毒成人身体功能的机制，以及将其转化为社区场所的方法。

DESCRIPTION (provided by applicant): The candidate is a promising young investigator with board certifications in Internal Medicine and Infectious Disease, and a Masters of Science degree in Clinical Investigation, who has made a substantial commitment to an academic career in patient-oriented research in aging and HIV. The career plan and research proposal are consistent with her long-term goal to become an independent clinical investigator, and leader in academic geriatric medicine and HIV. Older individuals represent an increasingly larger proportion of adults living with HIV infection in the United States. Reduced aerobic capacity, mitochondrial oxidative dysfunction and loss of lean muscle mass are problems that affect both HIV-infected and non-infected older adults. However sarcopenia and oxidative dysfunction may be more pronounced in the presence of HIV, with the deficits further compounded by the metabolic effects of antiretroviral therapy. Understanding the underlying mechanisms of limited functional performance in older HIV adults will allow us to design effective prevention and treatment strategies that will improve and preserve function in this rapidly growing older patient population. The objective of this proposal is to investigate the mechanisms by which aging affects physical functioning and aerobic capacity in HIV adults (AIM 1), and to determine if aerobic exercise training improves functional and cardiovascular performance in older HIV adults (AIM 2). Hypothesis #1. Reduced physical functioning with aging will be affected by baseline immune status in HIV adults, and will be similarly affected by medical comorbid conditions in HIV-infected vs. negative adults. Hypothesis #2. Skeletal muscle oxidative dysfunction is a central factor associated with reduced aerobic capacity and functional limitations in older HIV adults. Hypothesis #3. Aerobic exercise training will improve muscle oxidative dysfunction, and the associated functional limitations and reduced aerobic capacity in older HIV subjects compared to sedentary older HIV controls; however, improvements may be limited by the extent of sarcopenia and HIV-related myopathy. The proposed research will lay the foundation for subsequent studies that will investigate the optimal exercise-based rehabilitation strategies and the mechanisms by which they improve physical functioning in older HIV adults, and methods for their translation into community sites.