Identification of potential biomarkers associated with aging through in silico analysis
Fatih Atilla Bağcı1
, Dilek Pirim1,2,3
1Department of Molecular Biology and Genetics, Bursa Uludağ University, Institute of Natural and Applied Science, Bursa, Türkiye
2Department of Molecular Biology and Genetics, Bursa Uludağ University, Faculty of Arts & Science, Bursa, Türkiye
3Department of Translational Medicine, Bursa Uludağ University, Institute of Health Sciences, Bursa, Türkiye
Keywords: Aging, biomarkers, immune cell infiltration, in silico analysis, miRNA.
Abstract
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.
Cite this article as: Bağcı FA, Pirim D. Identification of potential biomarkers associated with aging through in silico analysis. D J Med Sci 2025;11(2):74-82. doi: 10.5606/ fng.btd.2025.188.
Conceptualization, methodology, formal analysis, investigation, data curation, visualization, writing-original draft: F.A.B.; Conceptualization, supervision, project administration, writing-review & editing: D.P.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.