Induction of autophagy by spermidine promotes longevity

被引：1184

作者：

Eisenberg, Tobias ^{[1
]}

Knauer, Heide ^{[1
]}

Schauer, Alexandra ^{[1
]}

Buettner, Sabrina ^{[1
]}

Ruckenstuhl, Christoph ^{[1
]}

Carmona-Gutierrez, Didac ^{[1
]}

Ring, Julia ^{[1
]}

Schroeder, Sabrina ^{[1
]}

Magnes, Christoph ^{[2
]}

Antonacci, Lucia ^{[1
]}

Fussi, Heike ^{[1
]}

Deszcz, Luiza ^{[3
,4
]}

Hartl, Regina ^{[3
,4
]}

Schraml, Elisabeth ^{[5
]}

Criollo, Alfredo ^{[6
,7
,8
]}

Megalou, Evgenia ^{[9
]}

Weiskopf, Daniela ^{[10
]}

Laun, Peter ^{[11
]}

Heeren, Gino ^{[11
]}

Breitenbach, Michael ^{[11
]}

Grubeck-Loebenstein, Beatrix ^{[10
]}

Herker, Eva ^{[12
]}

Fahrenkrog, Birthe ^{[13
]}

Froehlich, Kai-Uwe ^{[1
]}

Sinner, Frank ^{[2
]}

Tavernarakis, Nektarios ^{[9
]}

Minois, Nadege ^{[3
,4
]}

Kroemer, Guido ^{[6
,7
,8
]}

Madeo, Frank ^{[1
]}

机构：

[1] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

[2] Inst Med Technol & Hlth Management, Graz, Austria

[3] Res Inst Mol Pathol, A-1030 Vienna, Austria

[4] Austrian Acad Sci, Inst Mol Biotechnol IMBA, A-1010 Vienna, Austria

[5] Univ Nat Resources & Appl Life Sci, Inst Appl Microbiol, Vienna, Austria

[6] INSERM, U848, Villejuif, France

[7] Inst Gustave Roussy, F-94805 Villejuif, France

[8] Univ Paris 11, F-94805 Villejuif, France

[9] Inst Mol Biol & Biotechnol, Fdn Res & Technol Hellas, Iraklion 70013, Crete, Greece

[10] Austrian Acad Sci, Inst Biomed Ageing Res, A-6020 Innsbruck, Austria

[11] Salzburg Univ, Dept Cell Biol, Div Genet, A-5020 Salzburg, Austria

[12] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA

[13] Univ Basel, ME Mueller Inst Struct Biol, Biozentrum, CH-4056 Basel, Switzerland

来源：

NATURE CELL BIOLOGY | 2009年 / 11卷 / 11期

基金：

奥地利科学基金会;

关键词：

LIFE-SPAN EXTENSION; NECROTIC CELL-DEATH; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; BUDDING YEAST; REGULATES APOPTOSIS; CALORIE RESTRICTION; OXIDATIVE STRESS; GENE-EXPRESSION; MURINE SKIN;

D O I：

10.1038/ncb1975

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

引用

页码：1305 / U102

页数：33

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