Bioinformatics analysis reveals shared gene signatures and molecular mechanisms between periodontitis and rheumatoid arthritis in the context of aging

Abstract

Objective The interplay between periodontitis (PD) and rheumatoid arthritis (RA) is well recognized, with aging being a central risk factor for both. However, the shared aging-related molecular mechanisms remain unclear. We aimed to identify common aging-related hub genes linking PD and RA and elucidate their underlying functional mechanisms. Material and methods PD and RA gene expression profiles were obtained from Gene Expression Omnibus database. Crosstalk genes were identified via differential expression analysis and intersected with aging-related genes from GeneCards. Functional enrichment (GO/KEGG) was performed. Hub genes were screened using protein–protein interaction network analysis and two machine learning algorithms and validated with external datasets. Diagnostic performance was evaluated by nomogram and receiver operating characteristic analysis. Immune cell infiltration was analyzed using CIBERSORT. Results We identified 191 aging-related crosstalk genes, enriched in immune-inflammatory pathways. Five hub genes (RAC2, CSF2RB, IL2RG, ENTPD1, and IL10RA) were confirmed, showing significant overexpression in PD and RA tissues with excellent diagnostic value. Immune infiltration revealed coordinated dysregulation of plasma cells and γδ T cells in both diseases. Conclusions This study reveals shared aging-related genes, pathways, and immune cell dysregulation between PD and RA, elucidating how aging exacerbates both diseases through immune-inflammatory mechanisms. These findings provide a theoretical basis for novel biomarkers and therapies.