Yang Jialiang, Huang Tao, Petralia Francesca, Long Quan, Zhang Bin, Argmann Carmen, Zhao Yong, Mobbs Charles V, Schadt Eric E, Zhu Jun, Tu Zhidong
Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, 10029, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, 10029, USA.
Sci Rep. 2015 Oct 19;5:15145. doi: 10.1038/srep15145.
Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger "co-aging" than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.
衰老乃是最为重要的生物学过程之一,且是人类诸多与年龄相关疾病的已知风险因素。研究全身各组织中与年龄相关的转录组变化,可为全面理解这一基本过程提供宝贵信息。在本研究中,我们梳理了基因型-组织表达(GTEx)项目收集的近200名个体的9种组织中与年龄相关的基因表达变化。总体而言,我们发现衰老基因表达特征具有很强的组织特异性。然而,在许多组织中都观察到一些著名的衰老相关成分(如线粒体生物学)出现富集。我们观察到与年龄相关的基因表达变化存在不同程度的跨组织同步性,基于主成分分析,一些关键组织(如心脏和肺)显示出比其他组织更强的“共同衰老”现象。衰老基因特征与复杂疾病基因呈现出复杂的重叠模式,仅在某些情况下,我们才会看到它们在受相应疾病影响的组织中显著重叠。总之,我们的分析为多组织中与年龄相关基因表达的共同调控提供了新见解;它还展现了衰老与年龄相关疾病之间联系的组织特异性观点。