Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol

Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity.

Morselli, Eugenia
Galluzzi, Lorenzo
Kepp, Oliver
Criollo, Alfredo
Maiuri, Maria Chiara
Tavernarakis, Nektarios
Madeo, Frank
Kroemer, Guido
Item Type: 
Journal Article
Publication Title: 
Journal Abbreviation: 
Aging (Albany NY)
Publication Date: 
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 20157579 PMCID: PMC2815753

Turabian/Chicago Citation

Eugenia Morselli, Lorenzo Galluzzi, Oliver Kepp, Alfredo Criollo, Maria Chiara Maiuri, Nektarios Tavernarakis, Frank Madeo and Guido Kroemer. 2009-12. "Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol." Aging 1: 12: 961-970.

Wikipedia Citation

<ref> {{Cite journal | doi = | issn = 1945-4589 | volume = 1 | pages = 961-970 | last = Morselli | first = Eugenia | coauthors = Galluzzi, Lorenzo, Kepp, Oliver, Criollo, Alfredo, Maiuri, Maria Chiara, Tavernarakis, Nektarios, Madeo, Frank, Kroemer, Guido | title = Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol | journal = Aging | date = 2009-12 | pmid = | pmc = }} </ref>