Aging whole blood transcriptome reveals candidate genes for SARS-CoV-2-related vascular and immune alterations

AbstractThe risk of severe COVID-19 increases with age as older patients are at highest risk. Thus, there is an urgent need to identify how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with blood components during aging. We investigated the whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins interacting with viral proteins during aging. From 22 DEGs in aged blood,FASLG,CTSW,CTSE,VCAM1, andBAG3 were associated with immune response, inflammation, cell component and adhesion, and platelet activation/aggregation. Males and females older than 50  years old overexpressFASLG, possibly inducing a hyperinflammatory cascade. The expression of cathepsins (CTSW andCTSE) and the anti-apoptotic co-chaperone moleculeBAG3 also increased throughout aging in both genders. By exploring single-cell RNA-sequencing data from peripheral blood of SARS-CoV-2-infected patients, we foundFASLG andCTSW expressed in natural killer cells and CD8  + T lymphocytes, whereasBAG3 was expressed mainly in CD4  + T cells, naive T cells, and CD14 + monocytes. In addition, T cell exhaustion was associated with increased expression ofCCL4L2 andDUSP4 over blood aging.LAG3,PDCD1,TIGIT,VCAM1,HLA-DRA, andTOX also increased in individuals aged 60 –69 years old; conversely, theRGS2 gene decreased with aging. We further identified a distinct gene expression profile associated with typ...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research