Effect of Exercise Training on Inflammation and Function in HIV Infected Veterans

描述(由申请人提供)： 在老年人中，慢性炎症是导致身体功能不佳、肌肉无力、心血管疾病和死亡的独立危险因素。同样，感染艾滋病毒的成年人体内炎症生物标志物水平的增加独立地预测心血管疾病和死亡，而与免疫状态无关。感染艾滋病毒的成年人有氧能力差、肌肉无力和骨质疏松症的风险增加，所有这些都可能因慢性炎症而加速。然而，慢性炎症对这些结果的影响以及运动训练的效果尚不清楚。在HIV阴性的有舒张期功能障碍的成年人中，炎症和心脏纤维化的生物标记物可以预测心功能和死亡率。在患有舒张期功能障碍的HIV阴性老年成年人中，有氧运动训练可以增加16%的有氧能力。感染艾滋病毒的成年人患舒张期功能障碍的风险增加4倍。我们的初步数据表明，在无症状的HIV感染退伍军人中，舒张期功能障碍与较差的有氧能力有关。根据美国运动医学院(ACSM)的建议，对较年轻的艾滋病毒感染成年人进行的运动康复研究显示，有氧能力、肌肉无力和骨骼减少有所改善，但在较年长的艾滋病毒感染成年人中可用的数据有限。我们的初步数据显示，在感染艾滋病毒的老年成年人中，高强度有氧运动训练的耐受性很好，并通过 17%。对舒张期功能的影响，以及全身炎症和心脏纤维化的相关性，在这一人群中尚不清楚。本研究的目的是通过比较随机接受有氧和阻力运动训练和常规护理的老年HIV感染退伍军人，确定运动训练对导致身体功能低下的中枢(心血管)和外周(肌肉)损伤的影响。我们的假设是，渐进的有氧和阻力康复计划将增加有氧能力和肌肉力量，这将通过改善舒张期功能、增加肌肉质量和减少全身炎症来实现。为了验证这一假设，我们将对60名久坐不动的老年(50岁以上)感染艾滋病毒的退伍军人进行为期16周的随机试验，对其进行渐进式有氧和阻力训练与常规护理对照。我们将确定运动训练对有氧能力和舒张期功能的影响，以及它们与全身炎症和心脏纤维化生物标志物变化的关系(AIM 1)。我们还将确定运动训练对力量和肌肉质量的影响，以及它们与全身炎症生物标记物变化的关系(AIM 2)。退伍军人管理局是美国最大的艾滋病毒感染者医疗保健机构，拥有超过25,000名患者，其中的患者年龄在50岁以上。这项新的翻译研究的发现将为未来的机制研究提供基础，以调查运动训练的器官特异性影响，包括心脏重构和纤维化，以及骨骼肌炎症细胞因子的表达。总的来说，拟议的研究将推进我们的目标，即制定有效的康复战略，改善感染艾滋病毒的退伍军人的健康和功能独立性。 公共卫生相关性： 需要进行研究，以确定安全有效的运动康复计划，以预防和改善携带艾滋病毒的老年人的身体残疾。这个问题对退伍军人管理局来说非常重要。在2.5万名感染艾滋病毒的退伍军人中，大多数人年龄在50岁以上(%)。衰老和炎症的综合影响增加了感染艾滋病毒的老年退伍军人身体残疾的风险。这项转化性运动训练试验将研究有氧运动和阻力训练相结合的心脏和骨骼肌效应，以通过减少慢性炎症的有害后果来减缓艾滋病毒感染引起的衰老的功能衰退。这些发现将指导未来对骨骼肌心脏重塑和炎症的康复研究。拟议的研究将推进制定有效康复战略的目标，以改善感染艾滋病毒的老年退伍军人的健康。

DESCRIPTION (provided by applicant): In older adults, chronic inflammation is an independent risk factor for poor physical function, muscle weakness, cardiovascular disease, and mortality. Similarly, increased levels of biomarkers of inflammation in HIV-infected adults independently predict cardiovascular disease and death, regardless of immune status. HIV-infected adults have increased risk for poor aerobic capacity, muscle weakness and sarcopenia, all of which may be accelerated by chronic inflammation. Yet, the impact of chronic inflammation on these outcomes and the effect of exercise training is not well understood. In HIV negative adults with diastolic dysfunction, biomarkers of inflammation and cardiac fibrosis predict cardiac function and mortality. In elderly HIV negative adults with diastolic dysfunction, aerobic exercise training increases aerobic capacity 16%. HIV-infected adults have a 4- fold increased risk of diastolic dysfunction. Our preliminary data indicates that diastolic dysfunction is associated with poor aerobic capacity in asymptomatic HIV-infected veterans. Exercise rehabilitation studies in younger HIV-infected adults, based on American College of Sports Medicine (ACSM) recommendations, show improvements in aerobic capacity, muscle weakness and sarcopenia but limited data are available in older HIV-infected adults. Our preliminary data shows that high-intensity aerobic exercise training in older HIV- infected adults is well tolerated and increases aerobic capacity by 17%. The effects on diastolic function, and correlates of systemic inflammation and cardiac fibrosis, are unknown in this population. The objective of this study is to determine the effect o exercise training on the central (cardiovascular) and peripheral (muscular) impairments underlying poor physical function by comparing older HIV-infected veterans randomized to combined aerobic and resistance exercise training versus usual care. Our hypothesis is that a progressive aerobic and resistance rehabilitation program will increase aerobic capacity and muscle strength, which will be mediated by improved diastolic function, increased muscle mass, and decreased systemic inflammation. To test this hypothesis, we will conduct a randomized 16-week trial of progressive aerobic and resistance training versus usual care control in 60 sedentary older (50+ years) HIV- infected veterans. We will determine the effects of exercise training on aerobic capacity and diastolic function, and their relationship to changes in biomarkers of systemic inflammation and cardiac fibrosis (AIM 1). We will also determine the effect of exercise training on strength and muscle mass, and their relationship to changes in biomarkers of systemic inflammation (AIM 2). The VA is the largest health care provider for HIV-infected individuals in the United States with over 25,000 patients, of which 64% are over 50 years of age. Findings from this novel translational research will provide the foundation for future mechanistic research to investigate organ-specific effects of exercise training, including cardiac remodeling and fibrosis, and skeletal muscle expression of inflammatory cytokines. Collectively, the proposed research will advance our goal to develop effective rehabilitation strategies that improve the health and functional independence of HIV-infected veterans. PUBLIC HEALTH RELEVANCE: Research is needed to determine safe and effective exercise rehabilitation programs to prevent and improve physical disability in older adults living with HIV. This problem is of great importance to the VA. The majority of the 25 thousand HIV-infected veterans are over 50 years of age (64%). The combined effect of aging and inflammation increase the risk for physical disability in older HIV-infected veterans. This translational exercise training trial will examine he cardiac and skeletal muscle effects of combined aerobic exercise and resistance training to attenuate the functional declines of aging with HIV by reducing the deleterious consequences of chronic inflammation. Findings will guide future rehabilitation research on cardiac remodeling and inflammation of skeletal muscle. The proposed research will advance the goal to develop effective rehabilitation strategies that improve the health of older HIV-infected veterans.