A modular network model of aging

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...

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Main Authors: Huiling Xue, Bo Xian, Dong Dong, Kai Xia, Shanshan Zhu, Zhongnan Zhang, Lei Hou, Qingpeng Zhang, Yi Zhang, Jing‐Dong J Han
Format: Article
Language:English
Published: Springer Nature 2007-12-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb4100189
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author Huiling Xue
Bo Xian
Dong Dong
Kai Xia
Shanshan Zhu
Zhongnan Zhang
Lei Hou
Qingpeng Zhang
Yi Zhang
Jing‐Dong J Han
author_facet Huiling Xue
Bo Xian
Dong Dong
Kai Xia
Shanshan Zhu
Zhongnan Zhang
Lei Hou
Qingpeng Zhang
Yi Zhang
Jing‐Dong J Han
author_sort Huiling Xue
collection DOAJ
description 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.
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publisher Springer Nature
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series Molecular Systems Biology
spelling doaj-art-c0dd73ea7de24993b41e87e5bcb3d1b22025-08-24T12:01:57ZengSpringer NatureMolecular Systems Biology1744-42922007-12-013111110.1038/msb4100189A modular network model of agingHuiling Xue0Bo Xian1Dong Dong2Kai Xia3Shanshan Zhu4Zhongnan Zhang5Lei Hou6Qingpeng Zhang7Yi Zhang8Jing‐Dong J Han9Chinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChinese Academy of Sciences Key Laboratory of Molecular and Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1038/msb4100189agingcell metabolismsdifferentiationmodulenetworkregulation
spellingShingle Huiling Xue
Bo Xian
Dong Dong
Kai Xia
Shanshan Zhu
Zhongnan Zhang
Lei Hou
Qingpeng Zhang
Yi Zhang
Jing‐Dong J Han
A modular network model of aging
Molecular Systems Biology
aging
cell metabolisms
differentiation
module
network
regulation
title A modular network model of aging
title_full A modular network model of aging
title_fullStr A modular network model of aging
title_full_unstemmed A modular network model of aging
title_short A modular network model of aging
title_sort modular network model of aging
topic aging
cell metabolisms
differentiation
module
network
regulation
url https://doi.org/10.1038/msb4100189
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