Molecular mechanisms underlying genotype-dependent responses to dietary restriction

被引：104

作者：

Schleit, Jennifer ^{[1
]}

Johnson, Simon C. ^{[1
]}

Bennett, Christopher F. ^{[1
,2
]}

Simko, Marissa ^{[1
]}

Trongtham, Natalie ^{[1
]}

Castanza, Anthony ^{[1
]}

Hsieh, Edward J. ^{[3
]}

Moller, Richard M. ^{[1
]}

Wasko, Brian M. ^{[1
]}

Delaney, Joe R. ^{[1
,2
]}

Sutphin, George L. ^{[1
,2
]}

Carr, Daniel ^{[1
]}

Murakami, Christopher J. ^{[1
]}

Tocchi, Autumn ^{[1
]}

Xian, Bo ^{[4
]}

Chen, Weiyang ^{[4
]}

Yu, Tao ^{[4
]}

Goswami, Sarani ^{[1
]}

Higgins, Sean ^{[1
]}

Holmberg, Mollie ^{[1
]}

Jeong, Ki-Soo ^{[1
]}

Kim, Jin R. ^{[1
]}

Klum, Shannon ^{[1
]}

Liao, Eric ^{[1
]}

Lin, Michael S. ^{[1
]}

Lo, Winston ^{[1
]}

Miller, Hillary ^{[1
]}

Olsen, Brady ^{[1
]}

Peng, Zhao J. ^{[1
]}

Pollard, Tom ^{[1
]}

Pradeep, Prarthana ^{[1
]}

Pruett, Dillon ^{[1
]}

Rai, Dilreet ^{[1
]}

Ros, Vanessa ^{[1
]}

Singh, Minnie ^{[1
]}

Spector, Benjamin L. ^{[1
]}

Vander Wende, Helen ^{[1
]}

An, Elroy H. ^{[1
]}

Fletcher, Marissa ^{[1
]}

Jelic, Monika ^{[1
]}

Rabinovitch, Peter S. ^{[1
]}

MacCoss, Michael J. ^{[3
]}

Han, Jing-Dong J. ^{[4
]}

Kennedy, Brian K. ^{[5
,6
]}

Kaeberlein, Matt ^{[1
,6
]}

机构：

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

[2] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA

[3] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

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

[5] Buck Inst Age Res, Novato, CA USA

[6] Guangdong Med Coll, Inst Aging Res, Dongguan, Peoples R China

来源：

AGING CELL | 2013年 / 12卷 / 06期

关键词：

aging; replicative lifespan; longevity; yeast; dietary restriction; mitochondria; mitochondrial unfolded protein response; EXTENDS LIFE-SPAN; CALORIC RESTRICTION; MITOCHONDRIAL PROTEINS; PROHIBITINS; TRANSLATION; INHIBITION; LONGEVITY; EXTENSION; INCREASE; DISEASE;

D O I：

10.1111/acel.12130

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses to DR. The effect of DR on lifespan was determined for 166 single gene deletion strains in Saccharomyces cerevisiae. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR. Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mtUPR), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms.

引用

页码：1050 / 1061

页数：12

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