Identification of Hub Genes and Pathways Associated with Ageing in Diabetic Encephalopathy Based on Transcriptome...

This study aimed to identify key genes and pathways associated with ageing in diabetic encephalopathy (DE) through transcriptome analysis and to explore their roles and mechanisms in accelerating brain ageing in diabetes. We used db/db mice to establish a model of type 2 diabetes mellitus DE. Moreover, ribonucleic acid sequencing was performed on hippocampal tissue, and differentially expressed genes (DEGs) were analysed. Ageing-related DEGs (Ag-DEGs) were identified based on the GenAge and CellAge databases. A protein-protein interaction (PPI) network of Ag-DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and hub genes were identified using the Molecular Complex Detection and CytoHubba plugins of Cytoscape. Finally, immune infiltration analysis was conducted based on transcriptome data to investigate the role of immune cells in diabetic brain ageing. A total of 98 Ag-DEGs were identified, primarily involved in hypoxia, tumour necrosis factor-alpha signalling via nuclear factor kappa B, apoptosis and P53 pathways. The PPI network analysis identified 14 hub genes: HDAC1, IGF2, EGR1, BCL2, FOS, ATM, EGF, PARP1, MAPK3, APOE, SOX2, CAV1, HSPA5 and NFKBIA. These genes play significant roles in apoptosis pathways in cancer, lipid metabolism, atherosclerosis and human immunodeficiency virus-1 infection. Immune infiltration analysis revealed significant differences in the distribution of natural killer cells, resting mast cells and plasma cells within the diabetic brain. This study identified Ag-DEGs and hub genes in a DE model, revealing potential mechanisms of diabetes-accelerated brain ageing. These findings provide new insights into the pathological mechanisms of diabetic brain ageing and may offer new targets for therapeutic interventions.