An analysis of aging-related genes derived from the Genotype-Tissue Expression project (GTEx).
An analysis of aging-related genes derived from the Genotype-Tissue Expression project (GTEx).
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DOI：
10.1038/s41420-018-0093-y
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发表时间：
2018
影响因子：
7
通讯作者：
Cui Q
中科院分区：
文献类型：
--
作者：
Jia K;Cui C;Gao Y;Zhou Y;Cui Q
衰老是一个复杂的生物过程，目前还远未完全了解。分析不同年龄之间的转录差异可能有助于揭示衰老的遗传基础。本研究从GTEx计划中筛选出1573个与年龄相关的差异表达基因，分为上调的年龄相关基因(UAG)和下调的年龄相关基因(DAGs)。对UAGs、DAGs等基因在进化、表达、功能和分子网络等方面的特点进行了全面的描述和比较。分析表明，与DAGs相比，UAG更具聚集性，进化更快，组织特异性更强，积累了更多的单核苷酸多态(SNPs)和疾病基因。DAG具有较低的进化速率、较高的表达水平、较多的同源基因数、较小的系统发育年龄和较早的身体发育表达。UAG更有可能位于细胞外区域，并发生在免疫相关过程和癌症相关途径中。相比之下，DAG更有可能定位于细胞内，并在分解代谢和代谢过程中富含。此外，DAG在蛋白质-蛋白质相互作用(PPI)网络中也是至关重要的，而UAG对信令网络的影响更大。这项研究突出了健康人群中衰老转录格局的特征，这可能有助于未来对衰老过程的研究，并为年龄依赖的精确医学提供更广阔的视野。
Aging is a complex biological process that is far from being completely understood. Analyzing transcriptional differences across age might help uncover genetic bases of aging. In this study, 1573 differentially expressed genes, related to chronological age, from the Genotype-Tissue Expression (GTEx) project, were categorized as upregulated age-associated genes (UAGs) and downregulated age-associated genes (DAGs). Characteristics in evolution, expression, function and molecular networks were comprehensively described and compared for UAGs, DAGs and other genes. Analyses revealed that UAGs are more clustered, more quickly evolving, more tissue specific and have accumulated more single-nucleotide polymorphisms (SNPs) and disease genes than DAGs. DAGs were found with a lower evolutionary rate, higher expression level, greater homologous gene number, smaller phyletic age and earlier expression in body development. UAGs are more likely to be located in the extracellular region and to occur in both immune-relevant processes and cancer-related pathways. By contrast, DAGs are more likely to be located intracellularly and to be enriched in catabolic and metabolic processes. Moreover, DAGs are also critical in a protein–protein interaction (PPI) network, whereas UAGs have more influence on a signaling network. This study highlights characteristics of the aging transcriptional landscape in a healthy population, which may benefit future studies on the aging process and provide a broader horizon for age-dependent precision medicine.
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影响因子：
14.9
作者：
NCBI Resource Coordinators
通讯作者：
NCBI Resource Coordinators
影响因子：
14.9
作者：
Chen WH;Minguez P;Lercher MJ;Bork P
通讯作者：
Bork P
影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
14.9
作者：
Chatr-Aryamontri A;Oughtred R;Boucher L;Rust J;Chang C;Kolas NK;O'Donnell L;Oster S;Theesfeld C;Sellam A;Stark C;Breitkreutz BJ;Dolinski K;Tyers M
通讯作者：
Tyers M