In Silico Analysis of Age-Associated Immune Gene Expression Alterationsin Human Dermal Fibroblasts

Introduction: Aging is accompanied by progressive alterations in immune function and transcriptional regulation, yet the molecular mechanisms underlying these changes in human skin cells remain incompletely understood. This study aimed to investigate age-associated patterns of immune gene expression in human dermal fibroblasts using a comprehensive in silico transcriptomic approach. Methods: Publicly available RNA-seq data (GSE113957) from dermal fibroblasts of young (1– 29 years) and aged (≥60 years) individuals were analyzed. Principal component analysis (PCA) and hierarchical clustering of the top 1000 most variable genes were performed to assess transcriptomic separation by age. Differential expression analysis was conducted with false discovery rate (FDR) correction, and correlation analysis was applied to identify genes associated with chronological age. Cytokine, immune checkpoint, and senescence-related genes were examined in detail. Results: PCA and clustering revealed partial segregation between young and aged fibroblasts. Genome-wide analysis identified several differentially expressed genes, though only a subset met combined FDR and fold-change criteria. Cytokine and immune regulatory genes such as IL1B, FOXP3, and IRF7 showed modest downregulation with age, whereas interferon-stimulated genes (MX1, ISG15, IFIT1) were also reduced. In contrast, senescence markers (CDKN1A, CDKN2A) exhibited moderate upregulation in aged samples. Continuous age-correlation analysis identified additional genes significantly associated with aging. Discussion: The observed decline in immune- and interferon-related transcripts, alongside increased expression of senescence markers, supports the concept of immunosenescence in cutaneous fibroblasts. These transcriptomic patterns reflect impaired antiviral signaling and accumulation of senescent phenotypes, consistent with broader aging biology. The findings emphasize the utility of in silico methods to explore age-related immune dysregulation in human tissues. Conclusion: This study identifies age-associated alterations in cytokine and immune gene expression in dermal fibroblasts, suggesting that immune decline and cellular senescence jointly contribute to skin aging. The results provide a framework for future validation studies aimed at identifying molecular biomarkers of aging and potential therapeutic targets for healthy longevity.