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Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae

The concept that mutations cause aging phenotypes could not be directly tested previously due to inability to identify age-related mutations in somatic cells and determine their impact on organismal aging. Here, we subjected Saccharomyces cerevisiae to multiple rounds of replicative aging and assess...

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Autores principales: Kaya, Alaattin, Lobanov, Alexei V, Gladyshev, Vadim N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406665/
https://www.ncbi.nlm.nih.gov/pubmed/25702753
http://dx.doi.org/10.1111/acel.12290
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author Kaya, Alaattin
Lobanov, Alexei V
Gladyshev, Vadim N
author_facet Kaya, Alaattin
Lobanov, Alexei V
Gladyshev, Vadim N
author_sort Kaya, Alaattin
collection PubMed
description The concept that mutations cause aging phenotypes could not be directly tested previously due to inability to identify age-related mutations in somatic cells and determine their impact on organismal aging. Here, we subjected Saccharomyces cerevisiae to multiple rounds of replicative aging and assessed de novo mutations in daughters of mothers of different age. Mutations did increase with age, but their low numbers, < 1 per lifespan, excluded their causal role in aging. Structural genome changes also had no role. A mutant lacking thiol peroxidases had the mutation rate well above that of wild-type cells, but this did not correspond to the aging pattern, as old wild-type cells with few or no mutations were dying, whereas young mutant cells with many more mutations continued dividing. In addition, wild-type cells lost mitochondrial DNA during aging, whereas shorter-lived mutant cells preserved it, excluding a causal role of mitochondrial mutations in aging. Thus, DNA mutations do not cause aging in yeast. These findings may apply to other damage types, suggesting a causal role of cumulative damage, as opposed to individual damage types, in organismal aging.
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spelling pubmed-44066652015-06-01 Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae Kaya, Alaattin Lobanov, Alexei V Gladyshev, Vadim N Aging Cell Original Articles The concept that mutations cause aging phenotypes could not be directly tested previously due to inability to identify age-related mutations in somatic cells and determine their impact on organismal aging. Here, we subjected Saccharomyces cerevisiae to multiple rounds of replicative aging and assessed de novo mutations in daughters of mothers of different age. Mutations did increase with age, but their low numbers, < 1 per lifespan, excluded their causal role in aging. Structural genome changes also had no role. A mutant lacking thiol peroxidases had the mutation rate well above that of wild-type cells, but this did not correspond to the aging pattern, as old wild-type cells with few or no mutations were dying, whereas young mutant cells with many more mutations continued dividing. In addition, wild-type cells lost mitochondrial DNA during aging, whereas shorter-lived mutant cells preserved it, excluding a causal role of mitochondrial mutations in aging. Thus, DNA mutations do not cause aging in yeast. These findings may apply to other damage types, suggesting a causal role of cumulative damage, as opposed to individual damage types, in organismal aging. BlackWell Publishing Ltd 2015-06 2015-02-22 /pmc/articles/PMC4406665/ /pubmed/25702753 http://dx.doi.org/10.1111/acel.12290 Text en © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Original Articles
Kaya, Alaattin
Lobanov, Alexei V
Gladyshev, Vadim N
Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae
title Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae
title_full Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae
title_fullStr Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae
title_full_unstemmed Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae
title_short Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae
title_sort evidence that mutation accumulation does not cause aging in saccharomyces cerevisiae
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406665/
https://www.ncbi.nlm.nih.gov/pubmed/25702753
http://dx.doi.org/10.1111/acel.12290
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