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Autophagic Punctum

The life span-prolonging effect of Sirtuin-1 is mediated by autophagy

Eugenia Morselli, Maria Chiara Maiuri, Maria Markaki, Evgenia Megalou, Angela Pasparaki, Konstantinos Palikaras, Alfredo Criollo, Lorenzo Galluzzi, Shoaib Ahmad Malik, Ilio Vitale, Mickael Michaud, Frank Madeo, Nektarios Tavernarakis and Guido Kroemer

The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life span-extending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.

Punctum to: Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaris K, Galluzzi L, Criollo A, Malik SA, Madeo F, Tavernarakis N, Kroemer G. Caloric restriction and resveratrol prolong longevity via the sirtuin-1 dependent induction of autophagy. Cell Death Disease 2010; In press.

Authors

Eugenia Morselli

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France

Maria Chiara Maiuri

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France

Maria Markaki

Institute of Molecular Biology and Biotechnology; Foundation for Research and Technology; Vasilika Vouton; Crete, Greece

Evgenia Megalou

Institute of Molecular Biology and Biotechnology; Foundation for Research and Technology; Vasilika Vouton; Crete, Greece

Angela Pasparaki

Institute of Molecular Biology and Biotechnology; Foundation for Research and Technology; Vasilika Vouton; Crete, Greece

Konstantinos Palikaras

Institute of Molecular Biology and Biotechnology; Foundation for Research and Technology; Vasilika Vouton; Crete, Greece

Alfredo Criollo

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France

Lorenzo Galluzzi

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France

Shoaib Ahmad Malik

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France

Ilio Vitale

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France

Mickael Michaud

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France

Frank Madeo

Institute of Molecular Biosciences; University of Graz; Graz, Austria

Nektarios Tavernarakis Corresponding author: tavernarakis@imbb.forth.gr

Institute of Molecular Biology and Biotechnology; Foundation for Research and Technology; Vasilika Vouton; Crete, Greece

Guido Kroemer Corresponding author: kroemer@igr.fr

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Université Paris Sud-XI; Villejuif, France