a network-based approach on elucidating the multi-faceted nature of chronological aging in s. cerevisiae一个基于网络的方法阐明在酿酒酵母老化时间是多方面的.pdfVIP

A Network-Based Approach on Elucidating the Multi- Faceted Nature of Chronological Aging in S. cerevisiae Esra Borklu Yucel*, Kutlu O. Ulgen Department of Chemical Engineering, Bogazici University, Istanbul, Turkey Abstract Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: The reconstructed networks are of scale-free and hierarchical nature, following a power law model with c = 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,