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 Breitenbach; B Grubeck-Loebenstein; E Herker; B Fahrenkrog; KU Frohlich; F Sinner; N Tavernarakis; Nadege Blandine Minois; G Kroemer; F Madeo

doi:10.1038/ncb1975

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

School of Biology

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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 language	English
Pages (from-to)	1305-1314
Journal	Nature Cell Biology
Volume	11
Issue number	11
DOIs	https://doi.org/10.1038/ncb1975
Publication status	Published - 2009

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Eisenberg, T., Knauer, H., Schauer, A., Buttner, 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., ... Madeo, F. (2009). Induction of autophagy by spermidine promotes longevity. Nature Cell Biology, 11(11), 1305-1314. https://doi.org/10.1038/ncb1975

@article{08586c82bfc44d8eb016326892d02adb,

title = "Induction of autophagy by spermidine promotes longevity",

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.",

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

year = "2009",

doi = "10.1038/ncb1975",

language = "English",

volume = "11",

pages = "1305--1314",

journal = "Nature Cell Biology",

issn = "1476-4679",

publisher = "Nature publishing group",

number = "11",

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Eisenberg, T, Knauer, H, Schauer, A, Buttner, 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, Frohlich, KU, Sinner, F, Tavernarakis, N, Minois, NB, Kroemer, G & Madeo, F 2009, 'Induction of autophagy by spermidine promotes longevity', Nature Cell Biology, vol. 11, no. 11, pp. 1305-1314. https://doi.org/10.1038/ncb1975

TY - JOUR

T1 - Induction of autophagy by spermidine promotes longevity

AU - Eisenberg, T

AU - Knauer, H

AU - Schauer, A

AU - Buttner, S

AU - Ruckenstuhl, C

AU - Carmona-Gutierrez, D

AU - Ring, J

AU - Schroeder, S

AU - Magnes, C

AU - Antonacci, L

AU - Fussi, H

AU - Deszcz, L

AU - Hartl, R

AU - Schraml, E

AU - Criollo, A

AU - Megalou, E

AU - Weiskopf, D

AU - Laun, P

AU - Heeren, G

AU - Breitenbach, M

AU - Grubeck-Loebenstein, B

AU - Herker, E

AU - Fahrenkrog, B

AU - Frohlich, KU

AU - Sinner, F

AU - Tavernarakis, N

AU - Minois, Nadege Blandine

AU - Kroemer, G

AU - Madeo, F

PY - 2009

Y1 - 2009

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.

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U2 - 10.1038/ncb1975

DO - 10.1038/ncb1975

M3 - Article

SN - 1476-4679

VL - 11

SP - 1305

EP - 1314

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 11

ER -

Induction of autophagy by spermidine promotes longevity

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