THE UNCHARTED ROLE OF ERAP2 IN AGING: A BIOINFORMATICS PERSPECTIVE

Abstract

BackgroundAging is associated with significant changes in the immune system, leading to increased susceptibility to infections, reduced vaccine efficacy, and a higher risk of autoimmune diseases. However, the molecular mechanisms driving these immunological alterations remain incompletely understood. In this study, we performed differential gene expression analysis (DGEA) to identify genes implicated in immune aging and explored their functional significance through enrichment analysis. MethodsUsing publicly available transcriptomic data from aged versus young individuals, we conducted DGEA to identify significantly dysregulated genes. Functional enrichment analyses, including Gene Ontology (GO) and Reactome pathway analysis, were performed to uncover biological processes and pathways enriched in the differentially expressed genes. We specifically focused on ERAP2, a gene found to be differentially expressed in aging, and examined its expression across various tissues. Additionally, we reviewed existing literature to assess ERAP2s role in antigen presentation and immune regulation. ResultsOur analysis revealed significant enrichment of pathways related to antigen processing and presentation, peptide metabolism, and immune system regulation. ERAP2, an aminopeptidase involved in trimming peptides for MHC class I presentation, was highly associated with these processes. Interestingly, no direct KEGG pathway annotation was found for ERAP2, suggesting a potential gap in functional characterization. However, Reactome analysis confirmed its involvement in class I MHC-mediated antigen processing and immune system pathways, aligning with its known immunological role. The expression analysis across multiple tissues showed ERAP2 to be widely expressed in immune-related tissues, further supporting its relevance. ConclusionOur findings highlight the potentially underexplored role of ERAP2 in immune aging. The lack of KEGG pathway annotation suggests that its function in aging and immune modulation may not be fully characterized, presenting an opportunity for further research. Given its role in antigen presentation, ERAP2 may represent a critical factor in the declining immune function observed in aging individuals. Further experimental validation is required to establish its mechanistic involvement and potential as a therapeutic target for age-related immune dysfunction.