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Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification
Reduced supply of the amino acid methionine increases longevity across species through an as yet elusive mechanism. Here, we report that methionine restriction (MetR) extends yeast chronological lifespan in an autophagy-dependent manner. Single deletion of several genes essential for autophagy (ATG5...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006742/ https://www.ncbi.nlm.nih.gov/pubmed/24785424 http://dx.doi.org/10.1371/journal.pgen.1004347 |
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author | Ruckenstuhl, Christoph Netzberger, Christine Entfellner, Iryna Carmona-Gutierrez, Didac Kickenweiz, Thomas Stekovic, Slaven Gleixner, Christina Schmid, Christian Klug, Lisa Sorgo, Alice G. Eisenberg, Tobias Büttner, Sabrina Mariño, Guillermo Koziel, Rafal Jansen-Dürr, Pidder Fröhlich, Kai-Uwe Kroemer, Guido Madeo, Frank |
author_facet | Ruckenstuhl, Christoph Netzberger, Christine Entfellner, Iryna Carmona-Gutierrez, Didac Kickenweiz, Thomas Stekovic, Slaven Gleixner, Christina Schmid, Christian Klug, Lisa Sorgo, Alice G. Eisenberg, Tobias Büttner, Sabrina Mariño, Guillermo Koziel, Rafal Jansen-Dürr, Pidder Fröhlich, Kai-Uwe Kroemer, Guido Madeo, Frank |
author_sort | Ruckenstuhl, Christoph |
collection | PubMed |
description | Reduced supply of the amino acid methionine increases longevity across species through an as yet elusive mechanism. Here, we report that methionine restriction (MetR) extends yeast chronological lifespan in an autophagy-dependent manner. Single deletion of several genes essential for autophagy (ATG5, ATG7 or ATG8) fully abolished the longevity-enhancing capacity of MetR. While pharmacological or genetic inhibition of TOR1 increased lifespan in methionine-prototroph yeast, TOR1 suppression failed to extend the longevity of methionine-restricted yeast cells. Notably, vacuole-acidity was specifically enhanced by MetR, a phenotype that essentially required autophagy. Overexpression of vacuolar ATPase components (Vma1p or Vph2p) suffices to increase chronological lifespan of methionine-prototrophic yeast. In contrast, lifespan extension upon MetR was prevented by inhibition of vacuolar acidity upon disruption of the vacuolar ATPase. In conclusion, autophagy promotes lifespan extension upon MetR and requires the subsequent stimulation of vacuolar acidification, while it is epistatic to the equally autophagy-dependent anti-aging pathway triggered by TOR1 inhibition or deletion. |
format | Online Article Text |
id | pubmed-4006742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40067422014-05-09 Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification Ruckenstuhl, Christoph Netzberger, Christine Entfellner, Iryna Carmona-Gutierrez, Didac Kickenweiz, Thomas Stekovic, Slaven Gleixner, Christina Schmid, Christian Klug, Lisa Sorgo, Alice G. Eisenberg, Tobias Büttner, Sabrina Mariño, Guillermo Koziel, Rafal Jansen-Dürr, Pidder Fröhlich, Kai-Uwe Kroemer, Guido Madeo, Frank PLoS Genet Research Article Reduced supply of the amino acid methionine increases longevity across species through an as yet elusive mechanism. Here, we report that methionine restriction (MetR) extends yeast chronological lifespan in an autophagy-dependent manner. Single deletion of several genes essential for autophagy (ATG5, ATG7 or ATG8) fully abolished the longevity-enhancing capacity of MetR. While pharmacological or genetic inhibition of TOR1 increased lifespan in methionine-prototroph yeast, TOR1 suppression failed to extend the longevity of methionine-restricted yeast cells. Notably, vacuole-acidity was specifically enhanced by MetR, a phenotype that essentially required autophagy. Overexpression of vacuolar ATPase components (Vma1p or Vph2p) suffices to increase chronological lifespan of methionine-prototrophic yeast. In contrast, lifespan extension upon MetR was prevented by inhibition of vacuolar acidity upon disruption of the vacuolar ATPase. In conclusion, autophagy promotes lifespan extension upon MetR and requires the subsequent stimulation of vacuolar acidification, while it is epistatic to the equally autophagy-dependent anti-aging pathway triggered by TOR1 inhibition or deletion. Public Library of Science 2014-05-01 /pmc/articles/PMC4006742/ /pubmed/24785424 http://dx.doi.org/10.1371/journal.pgen.1004347 Text en © 2014 Ruckenstuhl et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Ruckenstuhl, Christoph Netzberger, Christine Entfellner, Iryna Carmona-Gutierrez, Didac Kickenweiz, Thomas Stekovic, Slaven Gleixner, Christina Schmid, Christian Klug, Lisa Sorgo, Alice G. Eisenberg, Tobias Büttner, Sabrina Mariño, Guillermo Koziel, Rafal Jansen-Dürr, Pidder Fröhlich, Kai-Uwe Kroemer, Guido Madeo, Frank Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification |
title | Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification |
title_full | Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification |
title_fullStr | Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification |
title_full_unstemmed | Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification |
title_short | Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification |
title_sort | lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006742/ https://www.ncbi.nlm.nih.gov/pubmed/24785424 http://dx.doi.org/10.1371/journal.pgen.1004347 |
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