PMID:18059442

Citation	Xue, H, Xian, B, Dong, D, Xia, K, Zhu, S, Zhang, Z, Hou, L, Zhang, Q, Zhang, Y and Han, JD (2007) A modular network model of aging. Mol. Syst. Biol. 3:147
Abstract	Many fundamental questions on aging are still unanswered or are under intense debate. These questions are frequently not addressable by examining a single gene or a single pathway, but can best be addressed at the systems level. Here we examined the modular structure of the protein-protein interaction (PPI) networks during fruitfly and human brain aging. In both networks, there are two modules associated with the cellular proliferation to differentiation temporal switch that display opposite aging-related changes in expression. During fly aging, another couple of modules are associated with the oxidative-reductive metabolic temporal switch. These network modules and their relationships demonstrate (1) that aging is largely associated with a small number, instead of many network modules, (2) that some modular changes might be reversible and (3) that genes connecting different modules through PPIs are more likely to affect aging/longevity, a conclusion that is experimentally validated by Caenorhabditis elegans lifespan analysis. Network simulations further suggest that aging might preferentially attack key regulatory nodes that are important for the network stability, implicating a potential molecular basis for the stochastic nature of aging.
Links	PubMed PMC2174624 Online version:10.1038/msb4100189
Keywords	Aging/genetics; Aging/physiology; Animals; Brain/metabolism; Caenorhabditis elegans/genetics; Caloric Restriction; Drosophila melanogaster/physiology; Gene Expression Regulation; Gene Regulatory Networks; Genes, Helminth; Homeostasis; Humans; Longevity; Models, Biological; Protein Binding; RNA Interference
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