Biomarkers for Muscle Function and Aging in Chronic HIV Infection

描述：在美国，艾滋病毒感染已成为一种慢性疾病，越来越多的证据表明，加速老化表型。到2015年，一半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HIV感染与持续性炎症、纤维化和与肌肉老化相关的虚弱状况的风险增加有关。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，然后预计会加速功能障碍，导致过早衰老表型。我们认为，慢性炎症促进了肌肉组织重塑的不平衡，导致加速的，潜在的亚临床肌肉纤维化，这可能会限制身体功能的长期艾滋病毒人群的年龄。我们将回顾一组接受稳定ART的高危HIV感染成人和人口统计学匹配的未感染成人，以评估以下三个具体目标：1.确定炎症是否与有效ART治疗的成人骨骼肌纤维化有关。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通路和炎症通路，并表征新型炎症抑制剂JQ 1、炎症抑制剂罗格列酮和纤维化抑制剂氯沙坦。如果在本研究中证实了纤维化，并且有活化TGF的证据？1信号，这些患者可以用抗纤维化药物治疗，如Losartan，一种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.