Induction of autophagy by spermidine promotes longevity

Eisenberg, Tobias and Knauer, Heide and Schauer, Alexandra and Büttner, Sabrina and Ruckenstuhl, Christoph and Carmona-Gutierrez, Didac and Ring, Julia and Schroeder, Sabrina and Magnes, Christoph and Antonacci, Lucia and Fussi, Heike and Deszcz, Luiza and Hartl, Regina and Schraml, Elisabeth and Criollo, Alfredo and Megalou, Evgenia and Weiskopf, Daniela and Laun, Peter and Heeren, Gino and Breitenbach, Michael and Grubeck-Loebenstein, Beatrix and Herker, Eva and Fahrenkrog, Birthe and Fröhlich, Kai-Uwe and Sinner, Frank and Tavernarakis, Nektarios and Minois, Nadege and Kroemer, Guido and Madeo, Frank. (2009) Induction of autophagy by spermidine promotes longevity. Nature Cell Biology , 11 (11). pp. 1305-1314.

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Official URL: https://edoc.unibas.ch/94113/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Fahrenkrog)
UniBasel Contributors:Fahrenkrog, Birthe
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Mar 2023 10:49
Deposited On:27 Mar 2023 10:49

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