A modular network model of aging.
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.
Xue
Huiling
H
Chinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Xian
Bo
B
Dong
Dong
D
Xia
Kai
K
Zhu
Shanshan
S
Zhang
Zhongnan
Z
Hou
Lei
L
Zhang
Qingpeng
Q
Zhang
Yi
Y
Han
Jing-Dong J
JD
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics; D031204:Caloric Restriction; D004331:Drosophila melanogaster / Q000502:physiology; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D017238:Genes, Helminth; D006706:Homeostasis; D006801:Humans; D008136:Longevity; D008954:Models, Biological; D011485:Protein Binding; D034622:RNA Interference