Department of Genetic Medicine, Weill Cornell Medicine, 1300 York Avenue, Box 164, New York, NY, 10065, USA.
Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Sci Rep. 2022 Feb 22;12(1):2966. doi: 10.1038/s41598-022-06373-7.
With highly active anti-retroviral therapy (HAART), higher incidence of airway abnormalities is common in the HIV population consistent with the concept of accelerated lung "aging". Our previous findings demonstrated that HIV induces human airway basal cells (BC) into destructive and inflammatory phenotypes. Since BC function as stem/progenitor cells of the small airway epithelium (SAE), responsible for self-renewal and differentiation of SAE, we hypothesized that BC from people living with HIV (PLWH) may have altered differentiation capacity that contribute to premature aging. The data demonstrates that BC from PLWH have impaired capacity to differentiate in vitro and senescent phenotypes including shortened telomeres, increased expression of β-galactosidase and cell cycle inhibitors, and mitochondrial dysfunction. In vitro studies demonstrated that BC senescence is partly due to adverse effects of HAART on BC. These findings provide an explanation for higher incidence of airway dysfunction and accelerated lung aging observed in PLWH.
高效抗逆转录病毒疗法 (HAART) 后，HIV 人群中气道异常的发生率较高，这与加速肺“衰老”的概念一致。我们之前的研究结果表明，HIV 可诱导人呼吸道基底细胞 (BC) 向破坏性和炎症性表型转化。由于 BC 作为小气道上皮 (SAE) 的干细胞/祖细胞，负责 SAE 的自我更新和分化，我们假设 HIV 感染者 (PLWH) 的 BC 可能具有改变的分化能力，从而导致过早衰老。数据表明，PLWH 的 BC 在体外分化能力受损，出现衰老表型，包括端粒缩短、β-半乳糖苷酶和细胞周期抑制剂表达增加以及线粒体功能障碍。体外研究表明，BC 衰老部分是由于 HAART 对 BC 的不良影响。这些发现为 HIV 感染者中观察到的气道功能障碍和加速肺衰老的发生率较高提供了一种解释。
