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PMID: 19801973 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Induction of autophagy by spermidine promotes longevity.

Nature cell biology ·Vol. 11 ·No. 11 ·2009-11-00 ·Pages 1305-14

Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, Fussi H, Deszcz L, Hartl R, Schraml E, Criollo A, Megalou E, Weiskopf D, Laun P, Heeren G, Breitenbach M, Grubeck-Loebenstein B, Herker E, Fahrenkrog B, Fröhlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F

Abstract

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.

MeSH Terms
Acetylation Adult Animals Autophagy/drug effects Caenorhabditis elegans/drug effects,immunology,physiology Drosophila melanogaster/drug effects,immunology,physiology Female HeLa Cells Histones/metabolism Humans Hydrogen-Ion Concentration Longevity/drug effects Male Mice Mice, Inbred C57BL Necrosis Saccharomyces cerevisiae/drug effects,immunology,physiology Spermidine/pharmacology
Chemicals
Histones Spermidine
Authors & Affiliations
29 authors, click to expand affiliations / ORCID
Eisenberg Tobias
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Knauer Heide
Schauer Alexandra
Büttner Sabrina
Ruckenstuhl Christoph
Carmona-Gutierrez Didac
Ring Julia
Schroeder Sabrina
Magnes Christoph
Antonacci Lucia
Fussi Heike
Deszcz Luiza
Hartl Regina
Schraml Elisabeth
Criollo Alfredo
Megalou Evgenia
Weiskopf Daniela
Laun Peter
Heeren Gino
Breitenbach Michael
Grubeck-Loebenstein Beatrix
Herker Eva
Fahrenkrog Birthe
Fröhlich Kai-Uwe
Sinner Frank
Tavernarakis Nektarios
Minois Nadege
Kroemer Guido
Madeo Frank
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb1975
Published
2009-11-00
Epub
2009-00-04
Pages
1305-14
Language
English
Region
England
NLM ID
100890575
Subset
IM
Grants
Austrian Science Fund FWF · S 9302 · Austria
Corrections
CommentIn
PMID: 19884883
External Links
PubMed source DOI: 10.1038/ncb1975 View journal details
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