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.
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.
Huiling
H
Xue
Bo
B
Xian
Dong
D
Dong
Kai
K
Xia
Shanshan
S
Zhu
Zhongnan
Z
Zhang
Lei
L
Hou
Qingpeng
Q
Zhang
Yi
Y
Zhang
Jing-Dong J
JD
Han
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