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Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence

Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling p...

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Autores principales: Weinberger, Martin, Mesquita, Ana, Carroll, Timothy, Marks, Laura, Yang, Hui, Zhang, Zhaojie, Ludovico, Paula, Burhans, William C.
Formato: Texto
Lenguaje:English
Publicado: Impact Journals LLC 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993800/
https://www.ncbi.nlm.nih.gov/pubmed/21076178
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author Weinberger, Martin
Mesquita, Ana
Carroll, Timothy
Marks, Laura
Yang, Hui
Zhang, Zhaojie
Ludovico, Paula
Burhans, William C.
author_facet Weinberger, Martin
Mesquita, Ana
Carroll, Timothy
Marks, Laura
Yang, Hui
Zhang, Zhaojie
Ludovico, Paula
Burhans, William C.
author_sort Weinberger, Martin
collection PubMed
description Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H(2)O(2), which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes.
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spelling pubmed-29938002010-11-30 Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence Weinberger, Martin Mesquita, Ana Carroll, Timothy Marks, Laura Yang, Hui Zhang, Zhaojie Ludovico, Paula Burhans, William C. Aging (Albany NY) Research Paper Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H(2)O(2), which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes. Impact Journals LLC 2010-10-27 /pmc/articles/PMC2993800/ /pubmed/21076178 Text en Copyright: © 2010 Weinberger 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
Weinberger, Martin
Mesquita, Ana
Carroll, Timothy
Marks, Laura
Yang, Hui
Zhang, Zhaojie
Ludovico, Paula
Burhans, William C.
Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_full Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_fullStr Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_full_unstemmed Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_short Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
title_sort growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993800/
https://www.ncbi.nlm.nih.gov/pubmed/21076178
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