Aging and Physical Functioning in HIV

应聘者描述(由申请人提供)：应聘者是一名有前途的年轻研究员，拥有内科和传染病委员会证书，临床调查理学硕士学位，致力于以患者为导向的老龄化和艾滋病毒研究的学术生涯。职业规划和研究建议与她成为一名独立的临床研究员和学术老年医学和艾滋病毒领域的领导者的长期目标是一致的。在美国感染艾滋病毒的成年人中，老年人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肉量减少都是影响感染艾滋病毒和未感染艾滋病毒的老年人的问题。然而，在艾滋病毒存在的情况下，骨骼减少和氧化功能障碍可能会更加明显，抗逆转录病毒治疗的代谢效应进一步加剧了这些缺陷。了解老年HIV患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，改善和保护这一快速增长的老年患者群体的功能。这项建议的目的是研究衰老影响HIV成年人身体机能和有氧能力的机制(AIM 1)，并确定有氧运动训练是否改善老年HIV成年人的功能和心血管表现(AIM 2)。假设1：随着年龄的增长，身体机能下降会受到HIV成人基线免疫状态的影响，在HIV感染者与阴性成年人中，同样会受到医学共病状况的影响。假设2：骨骼肌氧化功能障碍是老年HIV患者有氧能力降低和功能受限的一个中心因素。假设3：有氧运动训练将改善肌肉氧化功能障碍，与久坐不动的老年HIV对照组相比，老年HIV受试者的相关功能限制和有氧能力降低；然而，改善可能受到骨骼减少和HIV相关肌病的程度的限制。这项拟议的研究将为随后的研究奠定基础，这些研究将探索基于运动的最佳康复策略，以及这些策略改善老年艾滋病毒成年人身体功能的机制，以及将其转化为社区站点的方法。

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.