INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS

In a whole-genome screen for deletions that increase lifespan in S. cerevisiae, we identified increased Gcn4 signaling as a mediator of increased lifespan. Gcn4 is a nutrient-responsive transcription factor whose entire pathway is functionally conserved from yeast through humans. Accumulation of unc...

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Detalles Bibliográficos
Autores principales: McCormick, Mark, Robbins, Christine, Heath, Olivia, Westenskow, Marissa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Session 3195 (Symposium)
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6845789/
http://dx.doi.org/10.1093/geroni/igz038.2295
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author McCormick, Mark
Robbins, Christine
Heath, Olivia
Westenskow, Marissa
author_facet McCormick, Mark
Robbins, Christine
Heath, Olivia
Westenskow, Marissa
author_sort McCormick, Mark
collection PubMed
description In a whole-genome screen for deletions that increase lifespan in S. cerevisiae, we identified increased Gcn4 signaling as a mediator of increased lifespan. Gcn4 is a nutrient-responsive transcription factor whose entire pathway is functionally conserved from yeast through humans. Accumulation of uncharged tRNAs has been shown to upregulate Gcn4, and its mammalian ortholog, ATF4. Here we demonstrate that chemical inhibitors of tRNA synthetases significantly extend lifespan in both yeast and the nematode C. elegans, in a dose- and Gcn4-dependent manner.
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spelling pubmed-68457892019-11-18 INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS McCormick, Mark Robbins, Christine Heath, Olivia Westenskow, Marissa Innov Aging Session 3195 (Symposium) In a whole-genome screen for deletions that increase lifespan in S. cerevisiae, we identified increased Gcn4 signaling as a mediator of increased lifespan. Gcn4 is a nutrient-responsive transcription factor whose entire pathway is functionally conserved from yeast through humans. Accumulation of uncharged tRNAs has been shown to upregulate Gcn4, and its mammalian ortholog, ATF4. Here we demonstrate that chemical inhibitors of tRNA synthetases significantly extend lifespan in both yeast and the nematode C. elegans, in a dose- and Gcn4-dependent manner. Oxford University Press 2019-11-08 /pmc/articles/PMC6845789/ http://dx.doi.org/10.1093/geroni/igz038.2295 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Session 3195 (Symposium)
McCormick, Mark
Robbins, Christine
Heath, Olivia
Westenskow, Marissa
INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS
title INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS
title_full INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS
title_fullStr INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS
title_full_unstemmed INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS
title_short INCREASED LIFESPAN THROUGH ALTERED GCN4 / ATF-5 IN S. CEREVISIAE AND C. ELEGANS
title_sort increased lifespan through altered gcn4 / atf-5 in s. cerevisiae and c. elegans
topic Session 3195 (Symposium)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6845789/
http://dx.doi.org/10.1093/geroni/igz038.2295
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AT westenskowmarissa increasedlifespanthroughalteredgcn4atf5inscerevisiaeandcelegans

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