A pharmacological network for lifespan extension in Caenorhabditis elegans

One goal of aging research is to find drugs that delay the onset of age-associated disease. Studies in invertebrates, particularly Caenorhabditis elegans, have uncovered numerous genes involved in aging, many conserved in mammals. However, which of these encode proteins suitable for drug targeting i...

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Main Authors:	Ye, Xiaolan, Linton, James M, Schork, Nicholas J, Buck, Linda B, Petrascheck, Michael
Format:	Online
Language:	English
Published:	BlackWell Publishing Ltd 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955372/

id	pubmed-3955372
recordtype	oai_dc
spelling	pubmed-39553722015-02-19 A pharmacological network for lifespan extension in Caenorhabditis elegans Ye, Xiaolan Linton, James M Schork, Nicholas J Buck, Linda B Petrascheck, Michael Original Articles One goal of aging research is to find drugs that delay the onset of age-associated disease. Studies in invertebrates, particularly Caenorhabditis elegans, have uncovered numerous genes involved in aging, many conserved in mammals. However, which of these encode proteins suitable for drug targeting is unknown. To investigate this question, we screened a library of compounds with known mammalian pharmacology for compounds that increase C. elegans lifespan. We identified 60 compounds that increase longevity in C. elegans, 33 of which also increased resistance to oxidative stress. Many of these compounds are drugs approved for human use. Enhanced resistance to oxidative stress was associated primarily with compounds that target receptors for biogenic amines, such as dopamine or serotonin. A pharmacological network constructed with these data reveal that lifespan extension and increased stress resistance cluster together in a few pharmacological classes, most involved in intercellular signaling. These studies identify compounds that can now be explored for beneficial effects on aging in mammals, as well as tools that can be used to further investigate the mechanisms underlying aging in C. elegans. BlackWell Publishing Ltd 2014-04 2013-11-13 /pmc/articles/PMC3955372/ /pubmed/24134630 http://dx.doi.org/10.1111/acel.12163 Text en © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ye, Xiaolan Linton, James M Schork, Nicholas J Buck, Linda B Petrascheck, Michael
spellingShingle	Ye, Xiaolan Linton, James M Schork, Nicholas J Buck, Linda B Petrascheck, Michael A pharmacological network for lifespan extension in Caenorhabditis elegans
author_facet	Ye, Xiaolan Linton, James M Schork, Nicholas J Buck, Linda B Petrascheck, Michael
author_sort	Ye, Xiaolan
title	A pharmacological network for lifespan extension in Caenorhabditis elegans
title_short	A pharmacological network for lifespan extension in Caenorhabditis elegans
title_full	A pharmacological network for lifespan extension in Caenorhabditis elegans
title_fullStr	A pharmacological network for lifespan extension in Caenorhabditis elegans
title_full_unstemmed	A pharmacological network for lifespan extension in Caenorhabditis elegans
title_sort	pharmacological network for lifespan extension in caenorhabditis elegans
description	One goal of aging research is to find drugs that delay the onset of age-associated disease. Studies in invertebrates, particularly Caenorhabditis elegans, have uncovered numerous genes involved in aging, many conserved in mammals. However, which of these encode proteins suitable for drug targeting is unknown. To investigate this question, we screened a library of compounds with known mammalian pharmacology for compounds that increase C. elegans lifespan. We identified 60 compounds that increase longevity in C. elegans, 33 of which also increased resistance to oxidative stress. Many of these compounds are drugs approved for human use. Enhanced resistance to oxidative stress was associated primarily with compounds that target receptors for biogenic amines, such as dopamine or serotonin. A pharmacological network constructed with these data reveal that lifespan extension and increased stress resistance cluster together in a few pharmacological classes, most involved in intercellular signaling. These studies identify compounds that can now be explored for beneficial effects on aging in mammals, as well as tools that can be used to further investigate the mechanisms underlying aging in C. elegans.
publisher	BlackWell Publishing Ltd
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955372/
_version_	1612068099732799488

A pharmacological network for lifespan extension in Caenorhabditis elegans

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