Re-exploring the core genes and modules in the human frontal cortex during chronological aging: insights from network-based analysis of transcriptomic studies.
Re-exploring the core genes and modules in the human frontal cortex during chronological aging: insights from network-based analysis of transcriptomic studies.
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重新探索按时间顺序衰老过程中人类额叶皮层的核心基因和模块：基于网络的转录组研究分析的见解
DOI：
10.18632/aging.101589
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发表时间：
2018-10-20
期刊：
影响因子：
--
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Xu M;Liu Y;Huang Y;Wang J;Yan J;Zhang L;Zhang C
额叶皮质功能障碍是导致与年龄相关的行为和认知缺陷的基本病理，这些缺陷使老年人易患神经退行性疾病。已经确定，衰老会增加额叶皮质功能障碍的风险；然而，潜在的分子机制仍然难以捉摸。在这里，我们使用了一项综合荟萃分析，将5项额叶皮层微阵列研究与161名年轻人和155名老年人的联合样本人群结合起来。采用基于网络的分析方法描述了人类额叶皮层衰老的轮廓，以确定其表达随年龄变化的核心基因，并揭示这些基因之间的相互关系。我们发现组蛋白去乙酰化酶1 （HDAC1）和YES原癌基因1 （YES1）是两个上调最多的基因，而细胞分裂周期42 （CDC42）是老年人额叶皮层中下调的中心调控基因。定量PCR检测结果显示，衰老小鼠额叶皮层Hdac1、Yes1和Cdc42 mRNA水平发生相应变化。此外，对GSE48350数据集的分析证实了阿尔茨海默病中HDAC1、CDC42和YES1表达的类似变化，从而提供了衰老与阿尔茨海默病（AD）之间的分子联系。这种基于网络的分析框架可以为检测和监测大脑衰老提供新的策略。
Frontal cortical dysfunction is a fundamental pathology contributing to age-associated behavioral and cognitive deficits that predispose older adults to neurodegenerative diseases. It is established that aging increases the risk of frontal cortical dysfunction; however, the underlying molecular mechanism remains elusive. Here, we used an integrative meta-analysis to combine five frontal cortex microarray studies with a combined sample population of 161 younger and 155 older individuals. A network-based analysis was used to describe an outline of human frontal cortical aging to identify core genes whose expression changes with age and to reveal the interrelationships among these genes. We found that histone deacetylase 1 (HDAC1) and YES proto-oncogene 1 (YES1) are the two most upregulated genes, while cell division cycle 42 (CDC42) is the central regulatory gene decreased in the aged human frontal cortex. Quantitative PCR assays revealed corresponding changes in frontal cortical Hdac1, Yes1 and Cdc42 mRNA levels in an established aging mouse model. Moreover, analysis of the GSE48350 dataset confirmed similar changes in HDAC1, CDC42 and YES1 expression in Alzheimer's disease, thereby providing a molecular connection between aging and Alzheimer's disease (AD). This framework of network-based analysis could provide novel strategies for detecting and monitoring aging in the brain.
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影响因子：
--
作者：
Liu Y;Koyutürk M;Barnholtz-Sloan JS;Chance MR
通讯作者：
Chance MR
影响因子：
10.6
作者：
Datta D;Arion D;Corradi JP;Lewis DA
通讯作者：
Lewis DA
影响因子：
23.9
作者：
Florian, Maria Carolina;Doerr, Karin;Niebel, Anja;Daria, Deidre;Schrezenmeier, Hubert;Rojewski, Markus;Filippi, Marie-Dominique;Hasenberg, Anja;Gunzer, Matthias;Scharffetter-Kochanek, Karin;Zheng, Yi;Geiger, Hartmut
通讯作者：
Geiger, Hartmut
影响因子：
11
作者：
Hill, J. J.;Hashimoto, T.;Lewis, D. A.
通讯作者：
Lewis, D. A.
线粒体的蛋白质组学分析：它告诉我们有关衰老大脑的什么？
DOI：
10.18632/aging.101131
发表时间：
2016-12-13
期刊：
Aging
影响因子：
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作者：
Ingram T;Chakrabarti L
通讯作者：
Chakrabarti L