title: Aspirin extends the lifespan of Caenorhabditis elegans via AMPK and DAF-16/FOXO in dietary restriction pathway.
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.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
authors.forename: Qin-Li
authors.initials: QL
authors.lastname: Wan
authors.forename: Shan-Qing
authors.initials: SQ
authors.lastname: Zheng
authors.forename: Gui-Sheng
authors.initials: GS
authors.lastname: Wu
authors.forename: Huai-Rong
authors.initials: HR
authors.lastname: Luo
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D014450:Electron Transport Complex III / Q000235:genetics; D005508:Food Deprivation / Q000502:physiology; D051858:Forkhead Transcription Factors; D006358:Hot Temperature; D008136:Longevity / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009068:Movement / Q000187:drug effects; D009154:Mutation; D010641:Phenotype; D011494:Protein Kinases / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000187:drug effects; D034501:Telomere-Binding Proteins / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C487508:Eat-2 protein, C elegans; D051858:Forkhead Transcription Factors; D011978:Receptors, Nicotinic; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; C438752:clk-2 protein, C elegans; C108831:daf-16 protein, C elegans; C443102:Isp-1 protein, Caenorhabditis elegans; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D014450:Electron Transport Complex III; D001241:Aspirin