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Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner

Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of three fibrates, pharmacologi...

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Autores principales: Brandstädt, Sven, Schmeisser, Kathrin, Zarse, Kim, Ristow, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651519/
https://www.ncbi.nlm.nih.gov/pubmed/23603800
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author Brandstädt, Sven
Schmeisser, Kathrin
Zarse, Kim
Ristow, Michael
author_facet Brandstädt, Sven
Schmeisser, Kathrin
Zarse, Kim
Ristow, Michael
author_sort Brandstädt, Sven
collection PubMed
description Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of three fibrates, pharmacologically established serum lipid-lowering drugs and ligands of the nuclear receptor PPARalpha in mammals, are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans (wild-type N2 as well as two nhr-49-deficient strains, RB1716 and VC870) were maintained on agar plates and were fed E. coli strain OP50 bacteria. Bezafibrate, clofibrate, and fenofibrate were applied to the agar, respectively, to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. All three fibrates extended C. elegans N2 lifespan when applied at a concentration of 10 micromolar. Bezafibrate additionally extended C. elegans N2 lifespan at concentrations of 1 micromolar and 0.1 micromolar. In strains deficient for nhr-49, a functional orthologue of the mammalian peroxisome proliferator-activated receptor alpha (PPARalpha), all three compounds were incapable of extending lifespan. Taken together, fibrates promote C. elegans longevity in an NHR-49-dependent manner possibly by promoting mitohormesis and suggesting that these compounds may promote lifespan also in mammals.
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spelling pubmed-36515192013-05-14 Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner Brandstädt, Sven Schmeisser, Kathrin Zarse, Kim Ristow, Michael Aging (Albany NY) Research Paper Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of three fibrates, pharmacologically established serum lipid-lowering drugs and ligands of the nuclear receptor PPARalpha in mammals, are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans (wild-type N2 as well as two nhr-49-deficient strains, RB1716 and VC870) were maintained on agar plates and were fed E. coli strain OP50 bacteria. Bezafibrate, clofibrate, and fenofibrate were applied to the agar, respectively, to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. All three fibrates extended C. elegans N2 lifespan when applied at a concentration of 10 micromolar. Bezafibrate additionally extended C. elegans N2 lifespan at concentrations of 1 micromolar and 0.1 micromolar. In strains deficient for nhr-49, a functional orthologue of the mammalian peroxisome proliferator-activated receptor alpha (PPARalpha), all three compounds were incapable of extending lifespan. Taken together, fibrates promote C. elegans longevity in an NHR-49-dependent manner possibly by promoting mitohormesis and suggesting that these compounds may promote lifespan also in mammals. Impact Journals LLC 2013-04-08 /pmc/articles/PMC3651519/ /pubmed/23603800 Text en Copyright: © 2013 Brandstädt et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Paper
Brandstädt, Sven
Schmeisser, Kathrin
Zarse, Kim
Ristow, Michael
Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner
title Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner
title_full Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner
title_fullStr Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner
title_full_unstemmed Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner
title_short Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner
title_sort lipid-lowering fibrates extend c. elegans lifespan in a nhr-49/pparalpha-dependent manner
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651519/
https://www.ncbi.nlm.nih.gov/pubmed/23603800
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