Midlife gene expressions identify modulators of aging through dietary interventions

被引：52

作者：

Zhou, Bing ^{[2
,3
,4
]}

Yang, Liu ^{[1
]}

Li, Shoufeng ^{[1
]}

Huang, Jialiang ^{[2
,3
,4
]}

Chen, Haiyang ^{[5
]}

Hou, Lei ^{[2
,3
,4
]}

Wang, Jinbo ^{[4
,5
]}

Green, Christopher D. ^{[2
]}

Yan, Zhen ^{[6
,7
,8
]}

Huang, Xun ^{[5
]}

Kaeberlein, Matt ^{[9
]}

Zhu, Li ^{[10
]}

Xiao, Huasheng ^{[10
]}

Liu, Yong ^{[1
]}

Han, Jing-Dong J. ^{[2
]}

机构：

[1] Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Key Lab Computat Biol, Max Planck Partner Inst Computat Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[3] Chinese Acad Sci, Ctr Mol Syst Biol, Inst Genet & Dev Biol, Beijing 100101, Peoples R China

[4] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China

[5] Chinese Acad Sci, State Key Lab Mol Dev Biol, Inst Genet & Dev Biol, Beijing 100101, Peoples R China

[6] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Dept Med Cardiovasc Med, Charlottesville, VA 22908 USA

[7] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Dept Pharmacol, Charlottesville, VA 22908 USA

[8] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Ctr Skeletal Muscle Res, Charlottesville, VA 22908 USA

[9] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[10] Chinese Acad Sci, Key Lab Syst Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 19期

基金：

中国国家自然科学基金;

关键词：

systems biology; diet-induced obesity; ELEGANS LIFE-SPAN; MITOCHONDRIAL BIOGENESIS; TRANSCRIPTIONAL PROFILE; CAENORHABDITIS-ELEGANS; HUMAN BRAIN; C-ELEGANS; AGED MICE; RESTRICTION; PEROXISOMES; PATTERNS;

D O I：

10.1073/pnas.1119304109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. We found that pathways transcriptionally correlated with diet-modulated lifespan and physiological changes were enriched for lifespan-modifying genes. Intriguingly, mitochondrial gene expression correlated with lifespan and anticorrelated with aging-related pathological changes, whereas peroxisomal gene expression showed an opposite trend. Both organelles produce reactive oxygen species, a proposed causative factor of aging. This finding implicates a contribution of peroxisome to aging. Consistent with this hypothesis, lowering the expression levels of peroxisome proliferation genes decreased the cellular peroxide levels and extended the lifespan of Drosophila melanogaster and Caenorhabditis elegans. These findings show that transcriptional changes resulting from dietary interventions can effectively reflect causal factors in aging and identify previously unknown or under-appreciated longevity pathways, such as the peroxisome pathway.

引用

页码：E1201 / E1209

页数：9

共 46 条

[1] Resveratrol improves health and survival of mice on a high-calorie diet [J].