Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain.
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain.
Cells. 2022 Jan 20;11(3):348. doi: 10.3390/cells11030348.
The activity of sirtuin 1 (SIRT1), a class III histone deacetylase with a critical role in several biological functions, decreases with age and its deficiency is associated with many inflammatory and age-related diseases. It also regulates the chronic immune activation and viral latency during an HIV infection. The life-span and particularly the health span of HIV patients are substantially shortened; however, the participation of SIRT1 in these effects is not clear. We performed a prospective cross-sectional monocentric study that included 70 HIV-infected patients and 43 BMI-, age- and sex-matched uninfected individuals. We found that in the PBMCs of the HIV patients, mRNA levels were significantly lower ( < 0.0001). This decrease, which was corroborated at the protein level, occurred irrespectively of the antiretroviral regimen these patients received and was not significantly related to the general, HIV-related or comorbidity-related parameters. The levels of the major mitochondrial sirtuin were not altered. Moreover, the strong correlations of with the leukocyte markers and present in the uninfected individuals were absent in the HIV patients. In conclusion, this study showed that the PBMCs of the HIV patients displayed diminished SIRT1 levels and altered correlations of SIRT1 with markers of CD8 T cells and B cells, findings which may be relevant for understanding the complex pathogenic milieu in HIV patients.
SIRT1（沉默信息调节因子 1）活性随着年龄的增长而降低，它是一种具有重要生物学功能的 III 类组蛋白去乙酰化酶，其缺乏与许多炎症和与年龄相关的疾病有关。它还调节 HIV 感染期间慢性免疫激活和病毒潜伏。HIV 患者的寿命，特别是健康寿命大大缩短；然而，SIRT1 在此类影响中的参与尚不清楚。我们进行了一项前瞻性横断面单中心研究，纳入了 70 名 HIV 感染患者和 43 名 BMI、年龄和性别匹配的未感染个体。我们发现，HIV 患者的 PBMC 中 SIRT1 的 mRNA 水平显著降低（<0.0001）。这种降低在蛋白质水平上得到了证实，与患者接受的抗逆转录病毒治疗方案无关，与一般、HIV 相关或合并症相关参数也没有显著关系。主要线粒体 SIRT1 的水平没有改变。此外，未感染个体中 SIRT1 与白细胞标志物 和 的强烈相关性在 HIV 患者中不存在。总之，这项研究表明，HIV 患者的 PBMC 显示出 SIRT1 水平降低，以及 SIRT1 与 CD8 T 细胞和 B 细胞标志物的相关性改变，这些发现可能有助于理解 HIV 患者复杂的致病环境。
