Exploring molecular signatures related to the mechanism of aging in different brain regions by integrated bioinformatics

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Xinyue Tian¹  Xie Su¹  Menghua Chen¹  Bing Lin¹  Lu Xie²  Jing Li² 

[1] Department of Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Physiology, Pre-Clinical Science, Guangxi Medical University, Nanning, China;

关键词: brain aging;    brain regions;    molecular signatures;    neuroinflammation;    bioinformatics;    hub genes;   

DOI  :  10.3389/fnmol.2023.1133106

 received in 2022-12-28, accepted in 2023-02-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

The mechanism of brain aging is not fully understood. Few studies have attempted to identify molecular changes using bioinformatics at the subregional level in the aging brain. This study aimed to identify the molecular signatures and key genes involved in aging, depending on the brain region. Differentially expressed genes (DEGs) associated with aging of the cerebral cortex (CX), hippocampus (HC), and cerebellum (CB) were identified based on five datasets from the Gene Expression Omnibus (GEO). The molecular signatures of aging were explored using functional and pathway analyses. Hub genes of each brain region were determined by protein–protein interaction network analysis, and commonly expressed DEGs (co-DEGs) were also found. Gene–microRNAs (miRNAs) and gene–disease interactions were constructed using online databases. The expression levels and regional specificity of the hub genes and co-DEGs were validated using animal experiments. In total, 32, 293, and 141 DEGs were identified in aging CX, HC, and CB, respectively. Enrichment analysis indicated molecular changes related to leukocyte invasion, abnormal neurotransmission, and impaired neurogenesis due to inflammation as the major signatures of the CX, HC, and CB. Itgax is a hub gene of cortical aging. Zfp51 and Zfp62 were identified as hub genes involved in hippocampal aging. Itgax and Cxcl10 were identified as hub genes involved in cerebellar aging. S100a8 was the only co-DEG in all three regions. In addition, a series of molecular changes associated with inflammation was observed in all three brain regions. Several miRNAs interact with hub genes and S100a8. The change in gene levels was further validated in an animal experiment. Only the upregulation of Zfp51 and Zfp62 was restricted to the HC. The molecular signatures of aging exhibit regional differences in the brain and seem to be closely related to neuroinflammation. Itgax, Zfp51, Zfp62, Cxcl10, and S100a8 may be key genes and potential targets for the prevention of brain aging.

【 授权许可】

Unknown   
Copyright © 2023 Su, Xie, Li, Tian, Lin and Chen.