Induction of autophagy by spermidine promotes longevity

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

Research output: Contribution to journalArticlepeer-review

902 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1305-1314
JournalNature Cell Biology
Volume11
Issue number11
DOIs
Publication statusPublished - 2009

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