Biomarkers for Muscle Function and Aging in Chronic HIV Infection

描述：在美国，HIV感染已经成为一种慢性疾病，越来越多的证据表明加速衰老的表型。到2015年，超过一半的艾滋病毒感染者将达到50岁或以上。值得注意的是，慢性艾滋病毒感染与持续性炎症、纤维化和增加虚弱的风险有关--这些情况与肌肉老化有关。我们认为，慢性HIV感染中的持续性炎症促进了肌肉纤维化的加速，进而被预测为加速功能损害，导致过早衰老的表型。我们认为，慢性炎症促进肌肉组织重塑的失衡，导致加速的、潜在的亚临床肌肉纤维化，随着HIV人群的老龄化，这种纤维化可能会长期限制身体功能。我们将改写接受稳定抗逆转录病毒治疗的高危HIV感染成年人和人口统计学上匹配的未感染成年人的队列，以评估以下三个具体目标：1.确定炎症是否与服用有效抗逆转录病毒疗法的成年人骨骼肌纤维化有关。2.确定骨骼肌纤维化是否与身体功能有关。3.研究纤维化转化生长因子β1通路与炎症通路之间的潜在协同作用，以及新型炎症抑制剂JQ1、炎症抑制剂罗格列酮和纤维化抑制剂氯沙坦的特性。如果这项研究证实了纤维化，并且有证据表明转化生长因子-1信号被激活，这些患者可以使用抗纤维化药物，如洛沙坦，这是美国食品和药物管理局批准的一种在骨骼肌中具有有效抗纤维化特性的药物。

DESCRIPTION: In the United States, HIV infection has become a chronic disease with increasing evidence for an accelerated aging phenotype. By 2015, over half of HIV-infected individuals will be 50 years old or older. Notably, chronic HIV infection is associated with persistent inflammation, fibrosis and increased risk for frailty - conditions associated with muscl aging. We propose that persistent inflammation in chronic HIV infection promotes accelerated muscle fibrosis, which is then predicted to accelerate functional impairment, leading to a premature aging phenotype. We suggest that chronic inflammation promotes an imbalance in muscle tissue remodeling resulting in an accelerated, and potentially subclinical muscle fibrosis that is likely to limit physical function in the long term as the HIV population ages. We will recrit a cohort of at risk HIV-infected adults on stable ART and demographically matched uninfected adults to evaluate the following three specific aims: 1. Determine whether inflammation is related to skeletal muscle fibrosis in adults on effective ART. 2. Determine whether skeletal muscle fibrosis is related to physical function. 3. Characterize potential synergy between the fibrotic TGF?1 pathway and inflammatory pathway, and characterize the novel inflammatory inhibitor JQ1, the inflammatory inhibitor Rosiglitazone, and the fibrotic inhibitor Losartan. If fibrosis is confirmed in this study and there is evidence of activated TGF?1 signaling, these patients could be treated with anti-fibrotic agents such as Losartan, a Food and Drug Administration-approved drug with potent anti-fibrotic properties in skeletal muscle.