Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics Analysis
BackgroundGiven the arrival of the aging population has caused a series of social and economic problems, we aimed to explore the key genes underlying cognitively normal brain aging and its potential molecular mechanisms.MethodsGSE11882 was downloaded from Gene Expression Omnibus (GEO). The data from...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.833402/full |
| _version_ | 1818487579257864192 |
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| author | Jinling Xu Jinling Xu Hui Zhou Guangda Xiang Guangda Xiang |
| author_facet | Jinling Xu Jinling Xu Hui Zhou Guangda Xiang Guangda Xiang |
| author_sort | Jinling Xu |
| collection | DOAJ |
| description | BackgroundGiven the arrival of the aging population has caused a series of social and economic problems, we aimed to explore the key genes underlying cognitively normal brain aging and its potential molecular mechanisms.MethodsGSE11882 was downloaded from Gene Expression Omnibus (GEO). The data from different brain regions were divided into aged and young groups for analysis. Co-expressed differentially expressed genes (DEGs) were screened. Functional analysis, protein–protein interaction (PPI) network, microRNA (miRNA)-gene, and transcription factor (TF)-gene networks were performed to identify hub genes and related molecular mechanisms. AlzData database was used to elucidate the expression of DEGs and hub genes in the aging brain. Animal studies were conducted to validate the hub genes.ResultsCo-expressed DEGs contained 7 upregulated and 87 downregulated genes. The enrichment analysis indicated DEGs were mainly involved in biological processes and pathways related to immune-inflammatory responses. From the PPI network, 10 hub genes were identified: C1QC, C1QA, C1QB, CD163, FCER1G, VSIG4, CD93, CD14, VWF, and CD44. CD44 and CD93 were the most targeted DEGs in the miRNA-gene network, and TIMP1, HLA-DRA, VWF, and FGF2 were the top four targeted DEGs in the TF-gene network. In AlzData database, the levels of CD44, CD93, and CD163 in patients with Alzheimer’s disease (AD) were significantly increased than those in normal controls. Meanwhile, in the brain tissues of cognitively normal mice, the expression of CD44, CD93, and CD163 in the aged group was significantly lower than those in the young group.ConclusionThe underlying molecular mechanisms for maintaining healthy brain aging are related to the decline of immune-inflammatory responses. CD44, CD93, and CD 163 are considered as potential biomarkers. This study provides more molecular evidence for maintaining cognitively normal brain aging. |
| first_indexed | 2024-12-10T16:39:54Z |
| format | Article |
| id | doaj.art-fb09fd66c5b1428e8c29a02af3d9924a |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-10T16:39:54Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-fb09fd66c5b1428e8c29a02af3d9924a2022-12-22T01:41:17ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-03-011410.3389/fnagi.2022.833402833402Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics AnalysisJinling Xu0Jinling Xu1Hui Zhou2Guangda Xiang3Guangda Xiang4The First School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Endocrinology, General Hospital of Central Theater Command, Wuhan, ChinaDepartment of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, ChinaThe First School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Endocrinology, General Hospital of Central Theater Command, Wuhan, ChinaBackgroundGiven the arrival of the aging population has caused a series of social and economic problems, we aimed to explore the key genes underlying cognitively normal brain aging and its potential molecular mechanisms.MethodsGSE11882 was downloaded from Gene Expression Omnibus (GEO). The data from different brain regions were divided into aged and young groups for analysis. Co-expressed differentially expressed genes (DEGs) were screened. Functional analysis, protein–protein interaction (PPI) network, microRNA (miRNA)-gene, and transcription factor (TF)-gene networks were performed to identify hub genes and related molecular mechanisms. AlzData database was used to elucidate the expression of DEGs and hub genes in the aging brain. Animal studies were conducted to validate the hub genes.ResultsCo-expressed DEGs contained 7 upregulated and 87 downregulated genes. The enrichment analysis indicated DEGs were mainly involved in biological processes and pathways related to immune-inflammatory responses. From the PPI network, 10 hub genes were identified: C1QC, C1QA, C1QB, CD163, FCER1G, VSIG4, CD93, CD14, VWF, and CD44. CD44 and CD93 were the most targeted DEGs in the miRNA-gene network, and TIMP1, HLA-DRA, VWF, and FGF2 were the top four targeted DEGs in the TF-gene network. In AlzData database, the levels of CD44, CD93, and CD163 in patients with Alzheimer’s disease (AD) were significantly increased than those in normal controls. Meanwhile, in the brain tissues of cognitively normal mice, the expression of CD44, CD93, and CD163 in the aged group was significantly lower than those in the young group.ConclusionThe underlying molecular mechanisms for maintaining healthy brain aging are related to the decline of immune-inflammatory responses. CD44, CD93, and CD 163 are considered as potential biomarkers. This study provides more molecular evidence for maintaining cognitively normal brain aging.https://www.frontiersin.org/articles/10.3389/fnagi.2022.833402/fullbrain agingimmunityinflammatorydifferentially expressed geneshub genes |
| spellingShingle | Jinling Xu Jinling Xu Hui Zhou Guangda Xiang Guangda Xiang Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics Analysis Frontiers in Aging Neuroscience brain aging immunity inflammatory differentially expressed genes hub genes |
| title | Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics Analysis |
| title_full | Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics Analysis |
| title_fullStr | Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics Analysis |
| title_full_unstemmed | Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics Analysis |
| title_short | Identification of Key Biomarkers and Pathways for Maintaining Cognitively Normal Brain Aging Based on Integrated Bioinformatics Analysis |
| title_sort | identification of key biomarkers and pathways for maintaining cognitively normal brain aging based on integrated bioinformatics analysis |
| topic | brain aging immunity inflammatory differentially expressed genes hub genes |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.833402/full |
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