Induction of autophagy by spermidine promotes longevity - PubMed (original) (raw)

. 2009 Nov;11(11):1305-14.

doi: 10.1038/ncb1975. Epub 2009 Oct 4.

Heide Knauer, Alexandra Schauer, Sabrina Büttner, Christoph Ruckenstuhl, Didac Carmona-Gutierrez, Julia Ring, Sabrina Schroeder, Christoph Magnes, Lucia Antonacci, Heike Fussi, Luiza Deszcz, Regina Hartl, Elisabeth Schraml, Alfredo Criollo, Evgenia Megalou, Daniela Weiskopf, Peter Laun, Gino Heeren, Michael Breitenbach, Beatrix Grubeck-Loebenstein, Eva Herker, Birthe Fahrenkrog, Kai-Uwe Fröhlich, Frank Sinner, Nektarios Tavernarakis, Nadege Minois, Guido Kroemer, Frank Madeo

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Induction of autophagy by spermidine promotes longevity

Tobias Eisenberg et al. Nat Cell Biol. 2009 Nov.

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.

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