Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Aging (Albany NY). 2009 Dec 23;1(12):961-70.

Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.

Author information

  • 1INSERM, U848, F-94805 Villejuif, France.

Abstract

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.

KEYWORDS:

AMPK; Caenorhabditis elegans; IKK; Saccharomyces cerevisiae; mTOR; p53

PMID:
20157579
[PubMed - indexed for MEDLINE]
PMCID:
PMC2815753
Free PMC Article

Images from this publication.See all images (2)Free text

Figure 1.
Figure 2.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Impact Journals, LLC Icon for PubMed Central
    Loading ...
    Write to the Help Desk