Age-related but not longevity-related genes are found by weighted gene co-expression network analysis in the peripheral blood cells of humans

Age-related but not longevity-related genes are found by weighted gene co-expression network analysis in the peripheral blood cells of humans
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通过加权基因共表达网络分析在人类外周血细胞中发现与年龄相关但与长寿无关的基因

DOI:
10.1266/ggs.17-00052
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发表时间:
2018-12-01
影响因子:
1.1
通讯作者:
Zhang, Zhiyong
Zhang, Zhiyong
中科院分区:
生物学4区
文献类型:
--
作者:
Li, Chunhong;Mo, Dan;Zhang, Zhiyong

文献摘要

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人类的寿命是由遗传和环境因素决定的。潜在的长寿基因既没有特异性,也没有可重复性,与长寿相关的基因经常与年龄相关的基因混淆。为了区分特定的年龄和长寿相关基因,我们分析了莱顿长寿研究建立的基因表达综合数据集(GEO)。这些个体被分为长寿组(平均年龄93.4 ± 3.0岁)、长寿后代组(60.8 ± 6.1岁)和对照组(61.9 ± 6.9岁)。下载系列矩阵文件,并计算平均表达值。利用GEO2R在线鉴定长寿组与对照组之间以及长寿组与其后代之间的差异表达基因。共有507长寿和755年龄相关的DEG可视化使用维恩图。加权基因共表达网络分析(WGCNA)进行了长寿和年龄相关的DEG。年龄相关的颜色模块和基因进行了鉴定。其中绿色模块有46个与年龄相关的DEG,对年龄和衰老的生物学意义最大。对这46个DEG进行了基因本体论、京都基因和基因组百科全书和蛋白质相互作用途径分析,这些DEG主要富集在B细胞活化和受体信号传导途径中。CR2、VPREB3、MS4A1和CCR6被认为是衰老的最关键候选基因。
Human lifespan is determined by genetic and environmental factors. Potential longevity genes are neither specific nor reproducible, and longevity-related genes are constantly confused with age-related genes. To distinguish specific age- and longevity-related genes, we analyzed a Gene Expression Omnibus (GEO) dataset established by the Leiden Longevity Study. The individuals were classified into longevity (mean age, 93.4 +/- 3.0 years), longevity offspring (60.8 +/- 6.1) and control (61.9 +/- 6.9) groups. The series matrix files were downloaded, and average expression values were calculated. Differentially expressed genes (DEGs) between longevity and control groups and those between longevity and their offspring were identified by GEO2R online. A total of 507 longevity- and 755 age-related DEGs were visualized using a Venn diagram. Weighted gene co-expression network analysis (WGCNA) was performed on the longevity- and age-related DEGs. Age related color modules and genes were identified. However, no longevity-related modules or genes were found. The green module, with 46 age-related DEGs, was the most biologically significant to age and aging. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein protein interaction pathway analyses were conducted on these 46 DEGs, which are mainly enriched in B cell activation and receptor signaling pathways. CR2, VPREB3, MS4A1 and CCR6 were considered the most crucial candidate genes for aging.