Aspirin extends the lifespan of Caenorhabditis elegans via AMPK and DAF-16/FOXO in dietary restriction pathway

Qin-Li Wan; Shan-Qing Zheng; Gui-Sheng Wu; Huai-Rong Luo

doi:10.1016/j.exger.2013.02.020

Aspirin extends the lifespan of Caenorhabditis elegans via AMPK and DAF-16/FOXO in dietary restriction pathway

Exp Gerontol. 2013 May;48(5):499-506. doi: 10.1016/j.exger.2013.02.020. Epub 2013 Feb 26.

Authors

Qin-Li Wan¹, Shan-Qing Zheng, Gui-Sheng Wu, Huai-Rong Luo

Affiliation

¹ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.

PMID: 23485446
DOI: 10.1016/j.exger.2013.02.020

Abstract

Aspirin has been revealed to have many beneficial effects for health since it was discovered as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Here, we investigated the molecular mechanism of aspirin on the lifespan extension of Caenorhabditis elegans. Our results showed that aspirin could extend the lifespan of C. elegans, and increase its health span and stress resistance. The extension of lifespan by aspirin requires DAF-16/FOXO, AMPK, and LKB1, but not SIR-2.1. Aspirin could not extend the lifespan of the mutants of eat-2, clk-1, and isp-1. Aspirin could marginally extend the lifespan of long-live insulin-like receptor mutant daf-2(e1370) III. Taken together, aspirin might act through a dietary restriction-like mechanism, via increasing the AMP:ATP ratio and activating LKB1, subsequently activating AMPK, which stimulates DAF-16 to induce downstream effects through a DAF-16 translocation independent manner.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinase Kinases
Animals
Aspirin / administration & dosage
Aspirin / pharmacology*
Caenorhabditis elegans / drug effects*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / physiology
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / physiology*
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical / methods
Electron Transport Complex III / genetics
Food Deprivation / physiology
Forkhead Transcription Factors
Hot Temperature
Longevity / drug effects*
Longevity / genetics
Longevity / physiology
Movement / drug effects
Mutation
Phenotype
Protein Kinases / physiology*
Receptors, Nicotinic / genetics
Signal Transduction / physiology
Stress, Physiological / drug effects
Telomere-Binding Proteins / genetics
Transcription Factors / physiology*

Substances

Caenorhabditis elegans Proteins
Eat-2 protein, C elegans
Forkhead Transcription Factors
Receptors, Nicotinic
Telomere-Binding Proteins
Transcription Factors
clk-2 protein, C elegans
daf-16 protein, C elegans
Isp-1 protein, Caenorhabditis elegans
Protein Kinases
AMP-Activated Protein Kinase Kinases
Electron Transport Complex III
Aspirin