
An antidepressant that extends lifespan in adult caenorhabditis elegans
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ABSTRACT The mechanisms that determine the lifespan of an organism are still largely a mystery1. One goal of ageing research is to find drugs that would increase lifespan and vitality when
given to an adult animal. To this end, we tested 88,000 chemicals for the ability to extend the lifespan of adult _Caenorhabditis elegans_ nematodes. Here we report that a drug used as an
antidepressant in humans increases _C. elegans_ lifespan. In humans, this drug blocks neural signalling by the neurotransmitter serotonin. In _C. elegans_, the effect of the drug on lifespan
is reduced or eradicated by mutations that affect serotonin synthesis, serotonin re-uptake at synapses, or either of two G-protein-coupled receptors: one that recognizes serotonin and the
other that detects another neurotransmitter, octopamine. _In vitro_ studies show that the drug acts as an antagonist at both receptors. Testing of the drug on dietary-restricted animals or
animals with mutations that affect lifespan indicates that its effect on lifespan involves mechanisms associated with lifespan extension by dietary restriction. These studies indicate that
lifespan can be extended by blocking certain types of neurotransmission implicated in food sensing in the adult animal, possibly leading to a state of perceived, although not real,
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customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SEROTONIN AND DOPAMINE MODULATE AGING IN RESPONSE TO FOOD ODOR AND AVAILABILITY Article Open access 07 June 2022 AN ALTERNATIVE FOOD
SOURCE FOR METABOLISM AND LONGEVITY STUDIES IN _CAENORHABDITIS ELEGANS_ Article Open access 26 February 2021 ON THE BENEFITS OF THE TRYPTOPHAN METABOLITE 3-HYDROXYANTHRANILIC ACID IN
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Priess for critical reading of an earlier version of the manuscript, to members of the Priess and Buck laboratories for advice and discussions, and to J. Vazquez for technical assistance. We
thank S. Suo for providing the VN11 strain (_ser-3(ad1774_)_;tzIs3[cre::gfp, lin-15(+)])_ and J. Ying Sze for the _ser-4(ok512);yzEx205[ser-4(+); pRF4(rol-6(su1006))]_ strain. All other
strains were provided by the _Caenorhabditis_ Genetics Center, which is funded by the NIH, and the international _C. elegans_ Gene Knockout Consortium. This project was supported by the
Howard Hughes Medical Institute and the Ellison Medical Foundation. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Basic Sciences Division, Howard Hughes Medical Institute, Fred Hutchinson
Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA, Michael Petrascheck, Xiaolan Ye & Linda B. Buck Authors * Michael Petrascheck View author
publications You can also search for this author inPubMed Google Scholar * Xiaolan Ye View author publications You can also search for this author inPubMed Google Scholar * Linda B. Buck
View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Linda B. Buck. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION
The file contains Supplementary Figure 1 and Supplementary Tables 1-4 with Legends. (PDF 6204 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE
Petrascheck, M., Ye, X. & Buck, L. An antidepressant that extends lifespan in adult _Caenorhabditis elegans_. _Nature_ 450, 553–556 (2007). https://doi.org/10.1038/nature05991 Download
citation * Received: 31 July 2007 * Accepted: 11 October 2007 * Issue Date: 22 November 2007 * DOI: https://doi.org/10.1038/nature05991 SHARE THIS ARTICLE Anyone you share the following link
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