Discover the network underlying the connections between aging and age-related diseases.
Discover the network underlying the connections between aging and age-related diseases.
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DOI：
10.1038/srep32566
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发表时间：
2016-09-01
影响因子：
4.6
通讯作者：
Tu Z
中科院分区：
文献类型：
--
作者：
Yang J;Huang T;Song WM;Petralia F;Mobbs CV;Zhang B;Zhao Y;Schadt EE;Zhu J;Tu Z
尽管在过去的几十年里，我们对衰老的认识已经大大扩展，但衰老为什么以及如何导致与年龄有关的疾病（ARDs）的发展仍然难以捉摸。特别是，对衰老和ARDs之间联系的全球机制理解尚未建立。我们依靠一个名为“GeroNet”的网络模型来研究衰老与一百多种疾病之间的联系。通过评估与各种生物过程相对应的3000多个子网络中衰老基因与疾病基因之间的拓扑联系，我们发现与“对低氧水平的反应”、“胰岛素信号通路”、“细胞周期”等子网络中非ARD基因相比，衰老与ARD基因的联系更强。基于子网连通性，我们可以正确地“预测”一种疾病是否与年龄有关，并优先考虑与多个ARDs相关的生物过程。以阿尔茨海默病（AD）为例，GeroNet发现了可能在衰老和ARDs之间起关键作用的有意义的基因。老年痴呆症中由GeroNet识别的顶层模块与从大规模老年痴呆症大脑基因表达实验中识别的模块显著重叠，支持老年痴呆症确实揭示了该疾病涉及的潜在生物学过程。
Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named “GeroNet” to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to “response to decreased oxygen levels”, “insulin signalling pathway”, “cell cycle”, etc. Based on subnetwork connectivity, we can correctly “predict” if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer’s disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease.
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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：
10.1042/cs20120190
发表时间：
2013-02
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Kitada M;Kume S;Takeda-Watanabe A;Kanasaki K;Koya D
通讯作者：
Koya D
影响因子：
7.7
作者：
Gutierrez-Arcelus M;Lappalainen T;Montgomery SB;Buil A;Ongen H;Yurovsky A;Bryois J;Giger T;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Padioleau I;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
3.3
作者：
Liou GY;Storz P
通讯作者：
Storz P
DOI：
10.1186/2046-2395-3-6
发表时间：
2014
期刊：
Longevity & healthspan
影响因子：
--
作者：
Dai DF;Chiao YA;Marcinek DJ;Szeto HH;Rabinovitch PS
通讯作者：
Rabinovitch PS