Down-Regulation of the Longevity-Associated Protein SIRT1 in Peripheral Blood Mononuclear Cells of Treated HIV Patients

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-01, Vol.11 (3), p.348
• Main Authors: Gruevska, Aleksandra, Moragrega, Ángela B, Galindo, María J, Esplugues, Juan V, Blas-García, Ana, Apostolova, Nadezda
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Age; aging; AIDS; Antiretroviral drugs; Biomarkers - metabolism; Blood & organ donations; CD19 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; Chronic infection; Communication; Cross-Sectional Studies; Disease; Down-Regulation; Gene expression; Histone deacetylase; HIV; HIV Infections - drug therapy; HIV Infections - metabolism; Human immunodeficiency virus; Humans; inflammation; Latency; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Longevity; Lymphocytes B; Lymphocytes T; Metabolism; Mitochondria; mRNA; PBMC; Peripheral blood mononuclear cells; Prospective Studies; Proteins; SIRT1; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Sirtuins - genetics; Sirtuins - metabolism; Software; Womens health
• ISSN: 2073-4409; 2073-4409
• 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.