TY - JOUR
T1 - Induction of autophagy by spermidine promotes longevity
AU - Eisenberg, Tobias
AU - Knauer, Heide
AU - Schauer, Alexandra
AU - Büttner, Sabrina
AU - Ruckenstuhl, Christoph
AU - Carmona-Gutierrez, Didac
AU - Ring, Julia
AU - Schroeder, Sabrina
AU - Magnes, Christoph
AU - Antonacci, Lucia
AU - Fussi, Heike
AU - Deszcz, Luiza
AU - Hartl, Regina
AU - Schraml, Elisabeth
AU - Criollo, Alfredo
AU - Megalou, Evgenia
AU - Weiskopf, Daniela
AU - Laun, Peter
AU - Heeren, Gino
AU - Breitenbach, Michael
AU - Grubeck-Loebenstein, Beatrix
AU - Herker, Eva
AU - Fahrenkrog, Birthe
AU - Fröhlich, Kai Uwe
AU - Sinner, Frank
AU - Tavernarakis, Nektarios
AU - Minois, Nadege
AU - Kroemer, Guido
AU - Madeo, Frank
N1 - Funding Information:
We thank Ulrike Potocnik, Silvia Dichtinger, Arno Absenger and Elfgard Heintz for assistance. We are grateful to the Austrian Science Fund FWF (Austria) for grant S-9304-B05 (to F.M., S.B. and D.C.-G.), grant S-9303-B05 (to K.-U.F. and H.K.), grant LIPOTOX (to F.M. and S.B.), and grant S-9301-B05 (to B.G.-L.) and to the European Commission for project TransDeath (to K.-U.F. and C.R.), project APOSYS (to F.M., T.E. and G.K.) and project Lifespan (FP6 036894 to B.G.-L.). We are grateful to the Austrian Science Fund FWF (Vienna, Austria) for grants S9302-B05 (to M.B.) and to the European Commission (Brussels, Europe) for project MIMAGE (contract no. 512020; to M.B.).
PY - 2009/10/1
Y1 - 2009/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70449529855&partnerID=8YFLogxK
U2 - 10.1038/ncb1975
DO - 10.1038/ncb1975
M3 - Article
C2 - 19801973
AN - SCOPUS:70449529855
SN - 1465-7392
VL - 11
SP - 1305
EP - 1314
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 11
ER -