The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Aging Cell. 2023 Oct;22(10):e13951. doi: 10.1111/acel.13951. Epub 2023 Aug 7.
Biological aging in people with HIV (PWH) with prolonged successful antiretroviral therapy (ART) is convoluted and poorly defined. Here, we aimed to investigate the transcriptomics age estimator (TAE) in a cohort of 178 PWH on prolonged successful ART with immune reconstitution and viral suppression from the Copenhagen Comorbidity (COCOMO) cohort. We also used 143 clinical, demographical, and lifestyle factors to identify the confounders potentially responsible or associated with age acceleration. Among the PWH, 43% had an accelerated aging process (AAP), and 21% had decelerated aging process (DAP). DAP is linked with older age, European ancestry, and higher use of tenofovir disoproxil/alafenamide fumarate. A directionally class-based gene set enrichment analysis identified the upregulation of inflammatory pathways (e.g., cytokine and Retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways) and immune response like T-cell receptor signaling, antigen processing, and presentation in AAP and the downregulation of metabolic processes like oxidative phosphorylation, pyruvate metabolism.
在接受长期成功抗逆转录病毒治疗（ART）的 HIV 感染者（PWH）中，生物衰老较为复杂且定义不明确。在此，我们旨在通过哥本哈根合并症（COCOMO）队列中 178 名接受长期成功 ART 治疗且免疫重建和病毒抑制的 PWH 队列，研究转录组学年龄估算器（TAE）。我们还使用了 143 项临床、人口统计学和生活方式因素，以确定可能导致或与加速衰老相关的混杂因素。在 PWH 中，43%存在加速衰老过程（AAP），21%存在减速衰老过程（DAP）。DAP 与年龄较大、欧洲血统和更常使用替诺福韦二吡呋酯/丙酚替诺福韦有关。基于方向的基因集富集分析发现，AAP 中炎症途径（如细胞因子和 RIG-I 样受体信号通路）和免疫反应（如 T 细胞受体信号、抗原处理和呈递）上调，而代谢过程（如氧化磷酸化、丙酮酸代谢）下调。
