Biomarkers for Muscle Function and Aging in Chronic HIV Infection

描述：在美国，HIV感染已成为一种慢性疾病，越来越多的证据表明其加速衰老表型。到2015年，半数以上的艾滋病毒感染者将是50岁或50岁以上。值得注意的是，慢性艾滋病毒感染与持续炎症、纤维化和虚弱风险增加有关，而虚弱与肌肉衰老有关。我们提出慢性HIV感染中的持续炎症促进加速肌肉纤维化，然后预测这将加速功能损伤，导致过早衰老表型。我们认为慢性炎症促进肌肉组织重塑的不平衡，导致加速，潜在的亚临床肌肉纤维化，随着HIV人群的老龄化，这可能会长期限制身体功能。我们将招募一组接受稳定抗逆转录病毒治疗的艾滋病毒感染高危成人和人口统计学上匹配的未感染成人，以评估以下三个具体目标：确定在接受有效抗逆转录病毒治疗的成人中炎症是否与骨骼肌纤维化有关。2. 确定骨骼肌纤维化是否与身体功能有关。3. 表征纤维化TGF？1途径和炎症途径，并对新型炎症抑制剂JQ1、炎症抑制剂罗格列酮和纤维化抑制剂氯沙坦进行表征。如果本研究证实纤维化，并且有证据表明TGF？这些患者可以用抗纤维化药物治疗，如氯沙坦，这是一种经美国食品和药物管理局批准的药物，在骨骼肌中具有有效的抗纤维化特性。

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.