Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL.
Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL.
J Acquir Immune Defic Syndr. 2022 Feb 1;89(Suppl 1):S47-S55. doi: 10.1097/QAI.0000000000002864.
Virally suppressed chronic HIV-infected individuals on antiretroviral therapy experience similar immune impairments as HIV-uninfected elderly. However, they manifest symptoms of premature immune aging such as suboptimal responses to vaccination at a younger age. Mechanisms underlying premature immune aging are unclear.
The study site was University of Miami Miller School of Medicine.
In this study, we aimed to identify molecular signatures of aging in HIV-infected (HIV) individuals compared with age-matched healthy control (HC) participants. Transcriptomic profiles of peripheral blood mononuclear cells collected cross-sectionally from study participants were evaluated using RNA sequencing, and genes and pathways associated with age and HIV status were identified and compared between study groups. Generalized linear modeling was used to identify transcriptional signatures associated with age.
Despite that fewer differentially expressed genes between young (<40 yrs) and old (>59 yrs) were observed in the HIV group, metabolic and innate immune activation pathways were associated with increasing age in both HIV and HC. Age was also associated with pathways involved with T-cell immune activation in HC and with interferon signaling pathways in HIV. We observed signs of precocious immune aging at the transcriptional level in HIV and defined a transcriptional perturbation associated with innate immunity and glucose metabolism induced by aging in both HC and HIV.
In this study, we identified distinct molecular signatures predictive of age in HIV versus HC, which suggest precocious immune aging in HIV. Overall, our results highlight the molecular pathways of immune aging in both HC and HIV that may be targeted for additional mechanistic insights or in a therapeutic setting.
接受抗逆转录病毒疗法的病毒抑制性慢性 HIV 感染者经历着与 HIV 未感染者相似的免疫损伤。然而，他们表现出过早免疫衰老的症状，例如在更年轻时对疫苗接种的反应不佳。过早免疫衰老的机制尚不清楚。
本研究在美国迈阿密大学米勒医学院进行。
在这项研究中，我们旨在确定与年龄匹配的健康对照（HC）参与者相比，HIV 感染者（HIV）中与衰老相关的分子特征。使用 RNA 测序评估从研究参与者中横截面上采集的外周血单核细胞的转录组谱，并确定与年龄和 HIV 状态相关的基因和途径，并在研究组之间进行比较。广义线性模型用于识别与年龄相关的转录特征。
尽管 HIV 组中年轻（<40 岁）和年老（>59 岁）之间差异表达的基因较少，但代谢和固有免疫激活途径与 HIV 和 HC 中的年龄增加相关。年龄也与 HC 中与 T 细胞免疫激活相关的途径以及 HIV 中与干扰素信号通路相关的途径相关。我们在 HIV 中观察到转录水平上过早免疫衰老的迹象，并定义了与固有免疫和葡萄糖代谢相关的与衰老相关的转录扰动，这在 HC 和 HIV 中均存在。
在这项研究中，我们确定了 HIV 与 HC 中预测年龄的不同分子特征，这表明 HIV 中存在过早的免疫衰老。总体而言，我们的研究结果突出了 HC 和 HIV 中免疫衰老的分子途径，这可能为进一步的机制研究或治疗提供依据。
