Document Detail


A high-throughput screen for chemicals that increase the lifespan of Caenorhabditis elegans.
MedLine Citation:
PMID:  19686215     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One long-term goal of aging research is to find drugs that can delay aging and the onset of age-associated diseases. With this in mind, we screened 88,000 chemicals for the ability to increase the lifespan of Caenorhabditis elegans nematodes. We found that mianserin, a serotonin receptor antagonist used as an antidepressant in humans, can increase C. elegans lifespan when given only during adulthood. This effect is reduced or abolished by mutations that affect serotonin synthesis or serotonin reuptake at synapses. It also requires a serotonin receptor and an octopamine receptor, both of which are inhibited by the drug. Mianserin has no effect on the lifespan of animals with increased longevity due to dietary restriction or with a mutation that reduces food intake, indicating that the drug extends lifespan via mechanisms linked to dietary restriction. These studies indicate that lifespan can be increased by inhibiting certain kinds of neurotransmission previously implicated in food sensing, possibly by mimicking a physiological state associated with dietary restriction.
Authors:
Michael Petrascheck; Xiaolan Ye; Linda B Buck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1170     ISSN:  1749-6632     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-08-18     Completed Date:  2009-09-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  698-701     Citation Subset:  IM    
Affiliation:
Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Caenorhabditis elegans / drug effects*,  physiology
Longevity / drug effects*
Mianserin / pharmacology*
Octopamine / pharmacology*
Serotonin Antagonists / pharmacology*
Grant Support
ID/Acronym/Agency:
//Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Serotonin Antagonists; 104-14-3/Octopamine; 24219-97-4/Mianserin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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