Fatih Atilla Bağcı, Dilek Pirim
Demiroğlu Bilim Üniversitesi Florence Nightingale Tıp Dergisi - 2025;11(2):74-82
Objectives: In this study, we aim to investigate transcriptomic and immune alterations associated with chronological aging by analyzing the GSE237029 dataset, which includes peripheral blood mononuclear cell (PBMC) gene expression profiles from middle-aged and elderly individuals. Materials and methods: We analyzed the publicly available GSE237029 dataset comparing gene expression profiles in PBMCs between two age groups [n=4 middle-aged (35-50 years), n=5 older adults (75-89 years)]. We identified differentially expressed genes (DEGs), assessed their functional significance through pathway enrichment analyses, examined differences in immune cell composition, and investigated shared micro-ribonucleic acid (miRNA) and transcription factor (TF) regulators. Functional enrichment analyses were performed using g:Profiler. Immune cell composition differences were assessed via ImmuCellAI, and shared miRNA and TF regulators of DEGs were identified using miRDIP and TRRUST databases. Results: A total of 19 DEGs were identified, showing enrichment in pathways related to phosphatidylinositol 3-kinase signaling, signal transducer and activator of transcription (STAT) phosphorylation regulation, ubiquitin-mediated proteolysis, and cytokine-driven immune responses. Immune cell infiltration analysis revealed notable differences in induced regulatory T-cells, central memory T-cells, and effector memory T-cells across different age groups. Regulatory network analysis identified ten candidate miRNAs and six TFs as key upstream regulators of age-related DEGs. Notably, TEA domain transcription factor 4 within the Hippo-YAP/TAZ-TEAD pathway was recognized as a central TF targeting multiple aging-associated miRNAs, suggesting its potential role in influencing senescence and immune remodeling. Conclusion: Our in silico analysis identifies a set of PBMC-derived molecular signatures, including nuclear factor kappa-light-chain-enhancer of activated B cells/STAT-associated DEGs, specific miRNAs, and TF-miRNA regulatory axes that could serve as promising minimally invasive biomarkers for aging. These findings support combining transcriptomic and regulatory network profiling to better understand immune aging and guide targeted anti-aging strategies.
