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Autophagic Punctum

Spermidine: A novel autophagy inducer and longevity elixir

Frank Madeo, Tobias Eisenberg, Sabrina Büttner, Christoph Ruckenstuhl and Guido Kroemer

Spermidine is a ubiquitous polycation that is synthesized from putrescine and serves as a precursor of spermine. Putrescine, spermidine and spermine all are polyamines that participate in multiple known and unknown biological processes. Exogenous supply of spermidine prolongs the life span of several model organisms including yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans) and flies (Drosophila melanogaster) and significantly reduces age-related oxidative protein damage in mice, indicating that this agent may act as a universal anti-aging drug. Spermidine induces autophagy in cultured yeast and mammalian cells, as well as in nematodes and flies. Genetic inactivation of genes essential for autophagy abolishes the life span-prolonging effect of spermidine in yeast, nematodes and flies. These findings complement expanding evidence that autophagy mediates cytoprotection against a variety of noxious agents and can confer longevity when induced at the whole-organism level. We hypothesize that increased autophagic turnover of cytoplasmic organelles or long-lived proteins is involved in most if not all life span-prolonging therapies.

Punctum to: Eisenberg T, Knauer H, Schauer A, Büttner 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, Fröhlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 2009; 11:1305-14; PMID: 19801973; DOI: 10.1038/ncb1975

Authors

Frank Madeo Corresponding author: Frank.Madeo@uni-graz.at

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

Tobias Eisenberg

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

Sabrina Büttner

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

Christoph Ruckenstuhl

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

Guido Kroemer Corresponding author: kroemer@orange.fr

INSERM; U848; Villejuif, France; Institut Gustave Roussy; Villejuif, France; University Paris Sud; Paris-11; Villejuif, France