A network-based approach on elucidating the multi-faceted nature of chronological aging in S. cerevisiae.
A network-based approach on elucidating the multi-faceted nature of chronological aging in S. cerevisiae.
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DOI：
10.1371/journal.pone.0029284
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ulgen KO
中科院分区：
文献类型：
--
作者：
Borklu Yucel E;Ulgen KO
导致衰老并因此增加对年龄相关疾病的易感性的细胞机制是研究的中心主题，因为衰老是细胞命运的最终但尚未被理解的机制。已经对模型生物体进行了研究以阐明这些机制，并且酵母的时间老化已被广泛用作高等真核生物中氧化应激和有丝分裂后组织老化的模型。通过将蛋白质-蛋白质相互作用数据与基因本体术语相结合，重建了酵母的时间老化网络。然后根据节点的介数中心性值对重建的网络进行统计“调整”，以补偿计算机自动化方法。最初重建和调整的网络都经过拓扑和模块化分析。最后，通过汇集步骤特定的关键蛋白获得了最终的“心脏”网络，这是由描述调谐网络中多个信号通路的线性路径分解而产生的。重建的网络具有无标度和层次性质，遵循 γ = 1.49 的幂律模型。模块化和拓扑分析的结果验证了该调整方法的成功。模块化分析显着丰富的基因本体术语也证实了调谐网络捕获了时间老化的多因素性质。 TOR、Akt/PKB 和 cAMP/蛋白激酶 A 等多种信号通路之间的相互作用被总结在源自线性路径分析的“心脏”网络中。研究发现，TCB3、SNA3、PST2 和 YGR130C 四个基因的缺失可以延长酵母的实际寿命。重建的网络还可以通过针对线性路径分析中的不同信号通路，以及揭示在这些通路中发挥作用的新蛋白质，深入了解其他细胞机制对时间老化的影响。
Cellular mechanisms leading to aging and therefore increasing susceptibility to age-related diseases are a central topic of research since aging is the ultimate, yet not understood mechanism of the fate of a cell. Studies with model organisms have been conducted to ellucidate these mechanisms, and chronological aging of yeast has been extensively used as a model for oxidative stress and aging of postmitotic tissues in higher eukaryotes. The chronological aging network of yeast was reconstructed by integrating protein-protein interaction data with gene ontology terms. The reconstructed network was then statistically “tuned” based on the betweenness centrality values of the nodes to compensate for the computer automated method. Both the originally reconstructed and tuned networks were subjected to topological and modular analyses. Finally, an ultimate “heart” network was obtained via pooling the step specific key proteins, which resulted from the decomposition of the linear paths depicting several signaling routes in the tuned network. The reconstructed networks are of scale-free and hierarchical nature, following a power law model with γ = 1.49. The results of modular and topological analyses verified that the tuning method was successful. The significantly enriched gene ontology terms of the modular analysis confirmed also that the multifactorial nature of chronological aging was captured by the tuned network. The interplay between various signaling pathways such as TOR, Akt/PKB and cAMP/Protein kinase A was summarized in the “heart” network originated from linear path analysis. The deletion of four genes, TCB3, SNA3, PST2 and YGR130C, was found to increase the chronological life span of yeast. The reconstructed networks can also give insight about the effect of other cellular machineries on chronological aging by targeting different signaling pathways in the linear path analysis, along with unraveling of novel proteins playing part in these pathways.
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DOI：
10.1073/pnas.92.7.2984
发表时间：
1995-03-28
影响因子：
11.1
作者：
BHATTACHARYA, S;CHEN, L;POWERS, S
通讯作者：
POWERS, S
影响因子：
4.3
作者：
Batada NN;Hurst LD;Tyers M
通讯作者：
Tyers M
影响因子：
8
作者：
Creutz, CE;Snyder, SL;Schulz, TA
通讯作者：
Schulz, TA
影响因子：
--
作者：
Demczuk, Agnieszka;Guha, Nilanjan;Vancura, Ales
通讯作者：
Vancura, Ales
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW