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C22 disrupts embryogenesis and extends C. elegans lifespan

Caenorhabditis elegans is an instrumental model in aging research due to its large brood size, short lifespan, and malleable genetics. However, maintaining a synchronous nematode population for longevity studies is challenging and time consuming due to their quick rate of development and reproductio...

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Autores principales: Beydoun, Safa, Sridhar, Aditya, Tuckowski, Angela M., Wang, Emily, Leiser, Scott F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544340/
https://www.ncbi.nlm.nih.gov/pubmed/37791350
http://dx.doi.org/10.3389/fphys.2023.1241554
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author Beydoun, Safa
Sridhar, Aditya
Tuckowski, Angela M.
Wang, Emily
Leiser, Scott F.
author_facet Beydoun, Safa
Sridhar, Aditya
Tuckowski, Angela M.
Wang, Emily
Leiser, Scott F.
author_sort Beydoun, Safa
collection PubMed
description Caenorhabditis elegans is an instrumental model in aging research due to its large brood size, short lifespan, and malleable genetics. However, maintaining a synchronous nematode population for longevity studies is challenging and time consuming due to their quick rate of development and reproduction. Multiple methods are employed in the field, ranging from worm strains with temperature dependent sterility to DNA replication inhibitors such as 5′-fluorodeoxyuridine (FUdR). In this study, we characterize a small molecule (C22) that impairs eggshell integrity and disrupts early embryogenesis to determine its applicability as a potential FUdR alternative. We find that C22 prevents egg hatching in a concentration dependent manner. However, it extends the lifespan of wild type worms and can induce FMO-2, a longevity regulating enzyme downstream of dietary restriction. Our results suggest that C22 is unlikely to be widely useful as an alternative to FUdR but its mechanism for lifespan extension may be worth further investigation.
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spelling pubmed-105443402023-10-03 C22 disrupts embryogenesis and extends C. elegans lifespan Beydoun, Safa Sridhar, Aditya Tuckowski, Angela M. Wang, Emily Leiser, Scott F. Front Physiol Physiology Caenorhabditis elegans is an instrumental model in aging research due to its large brood size, short lifespan, and malleable genetics. However, maintaining a synchronous nematode population for longevity studies is challenging and time consuming due to their quick rate of development and reproduction. Multiple methods are employed in the field, ranging from worm strains with temperature dependent sterility to DNA replication inhibitors such as 5′-fluorodeoxyuridine (FUdR). In this study, we characterize a small molecule (C22) that impairs eggshell integrity and disrupts early embryogenesis to determine its applicability as a potential FUdR alternative. We find that C22 prevents egg hatching in a concentration dependent manner. However, it extends the lifespan of wild type worms and can induce FMO-2, a longevity regulating enzyme downstream of dietary restriction. Our results suggest that C22 is unlikely to be widely useful as an alternative to FUdR but its mechanism for lifespan extension may be worth further investigation. Frontiers Media S.A. 2023-09-18 /pmc/articles/PMC10544340/ /pubmed/37791350 http://dx.doi.org/10.3389/fphys.2023.1241554 Text en Copyright © 2023 Beydoun, Sridhar, Tuckowski, Wang and Leiser. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Beydoun, Safa
Sridhar, Aditya
Tuckowski, Angela M.
Wang, Emily
Leiser, Scott F.
C22 disrupts embryogenesis and extends C. elegans lifespan
title C22 disrupts embryogenesis and extends C. elegans lifespan
title_full C22 disrupts embryogenesis and extends C. elegans lifespan
title_fullStr C22 disrupts embryogenesis and extends C. elegans lifespan
title_full_unstemmed C22 disrupts embryogenesis and extends C. elegans lifespan
title_short C22 disrupts embryogenesis and extends C. elegans lifespan
title_sort c22 disrupts embryogenesis and extends c. elegans lifespan
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544340/
https://www.ncbi.nlm.nih.gov/pubmed/37791350
http://dx.doi.org/10.3389/fphys.2023.1241554
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