Identifying the role of aging-related genes in intracranial aneurysms through bioinformatics analysis

Intracranial aneurysm(IA) are among the most common cerebrovascular diseases, and their rupture can lead to severe consequences. Aging plays a significant role in the onset and progression of many diseases, yet it remains understudied in the context of intracranial aneurysms. The aim of this study is to investigate the role of aging-related genes in the development of intracranial aneurysms using public databases, in order to understand the underlying biological mechanisms.  METHODS: Gene expression profiles for intracranial aneurysms were downloaded from the GEO database. Human aging-related genes were obtained from the HAGR website. Differentially expressed gene analysis and WGCNA were used to identify core hub genes. GO and KEGG enrichment analyses were conducted to determine the potential biological functions and pathways that these differentially expressed aging-related genes in intracranial aneurysms might be involved in. Based on the hub genes, co-expression gene networks and Gene-TF-miRNA regulatory networks were constructed. Further exploration of drug-gene interactions was conducted to screen potential target drugs.

Through the intersection of aging-related genes and differentially expressed genes in IA, 32 common differentially expressed genes were identified, with 20 genes upregulated and 12 genes downregulated. GO enrichment analysis showed that these genes were mainly involved in epithelial cell proliferation and regulation, peptide enzyme activity modulation, and metabolic Homeostasis. KEGG enrichment analysis showed that these genes were primarily involved in the adipocytokine signaling pathway, growth Hormone synthesis,secretion and action, neurotrophin signaling pathway, and longevity regulating pathway. WGCNA was used to identify genes highly correlated with the IA phenotype, and an intersection with the 32 differentially expressed aging-related genes yielded 11 candidate Hub DEARGs. The expression of the candidate Hub DEARGs was validated using an external dataset, ultimately confirming 4 hub DEARGs related to intracranial aneurysms. Among them, NGFR and ADCY5 were downregulated, while BUB1B and SERPINE1 were upregulated.  CONCLUSIONS: This study identified four aging-related genes, NGFR, ADCY5, SERPINE1, and BUB1B, that are associated with intracranial aneurysms. This provides new insights into the molecular mechanisms underlying the development of intracranial aneurysms. The identified core genes provide promising leads for further experimental research to explore the pathogenesis of the disease.