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A pharmacological network for lifespan extension in Caenorhabditis elegans

Ye, Xiaolan and Linton, James M. and Schork, Nicholas J. and Buck, Linda B. and Petrascheck, Michael (2014) A pharmacological network for lifespan extension in Caenorhabditis elegans. Aging Cell, 13 (2). pp. 206-215. ISSN 1474-9718. PMCID PMC3955372.

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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.

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Additional Information:© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. 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. Issue online: 11 March 2014; Version of record online: 13 November 2013; Accepted manuscript online: 17 October 2013; Manuscript Accepted: 3 September 2013. We wish to thank members of the Buck laboratory for helpful discussions and B. Conti and L. Wiseman for comments on an earlier version of the manuscript. We would also like to thank D. Petrascheck, R. Folk, and K. Guthrie for help with the parametric survival time model. This project was supported by the Howard Hughes Medical Institute (L.B.B.) and grants from the Ellison Medical Foundation (L.B.B.) and the National Institutes of Health (NIA, P01 AG028054) (L.B.B.) (DP2 OD008398) (M.P.). NJS is funded in part by the NIA Longevity Consortium grant 2 U19 AG023122 as well as grant 8UL1 TR000109). Nematode strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). Author contributions: MP and LBB conceived the project, MP, XY, and JML designed and conducted experiments, NS and MP analyzed data, and MP and LBB wrote the paper. We declare that the authors have no interests, financial or otherwise, that could be perceived as biasing the results or discussion reported in this paper.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Ellison Medical FoundationUNSPECIFIED
NIHDP2 OD008398
NIH2 U19 AG023122
NIH8UL1 TR000109
NIHP40 OD010440
Subject Keywords:aging; dopamine; drugs; oxidative stress; pharmaceutical; serotonin
Issue or Number:2
PubMed Central ID:PMC3955372
Record Number:CaltechAUTHORS:20170329-140243650
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Official Citation:Ye, X., Linton, J. M., Schork, N. J., Buck, L. B. and Petrascheck, M. (2014), A pharmacological network for lifespan extension in Caenorhabditis elegans. Aging Cell, 13: 206–215. doi:10.1111/acel.12163
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75516
Deposited By: Tony Diaz
Deposited On:29 Mar 2017 21:14
Last Modified:03 Oct 2019 16:51

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