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...
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2014
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oai:doaj.org-article:2513812671d248ae85a0d77c88148d652021-11-18T06:20:50ZLifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification.1553-73901553-740410.1371/journal.pgen.1004347https://doaj.org/article/2513812671d248ae85a0d77c88148d652014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24785424/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Reduced 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.Christoph RuckenstuhlChristine NetzbergerIryna EntfellnerDidac Carmona-GutierrezThomas KickenweizSlaven StekovicChristina GleixnerChristian SchmidLisa KlugAlice G SorgoTobias EisenbergSabrina BüttnerGuillermo MariñoRafal KozielPidder Jansen-DürrKai-Uwe FröhlichGuido KroemerFrank MadeoPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 10, Iss 5, p e1004347 (2014) |
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DOAJ |
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| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Christoph Ruckenstuhl Christine Netzberger Iryna Entfellner Didac Carmona-Gutierrez Thomas Kickenweiz Slaven Stekovic Christina Gleixner Christian Schmid Lisa Klug Alice G Sorgo Tobias Eisenberg Sabrina Büttner Guillermo Mariño Rafal Koziel Pidder Jansen-Dürr Kai-Uwe Fröhlich Guido Kroemer Frank Madeo Lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification. |
| 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 |
article |
| author |
Christoph Ruckenstuhl Christine Netzberger Iryna Entfellner Didac Carmona-Gutierrez Thomas Kickenweiz Slaven Stekovic Christina Gleixner Christian Schmid Lisa Klug Alice G Sorgo Tobias Eisenberg Sabrina Büttner Guillermo Mariño Rafal Koziel Pidder Jansen-Dürr Kai-Uwe Fröhlich Guido Kroemer Frank Madeo |
| author_facet |
Christoph Ruckenstuhl Christine Netzberger Iryna Entfellner Didac Carmona-Gutierrez Thomas Kickenweiz Slaven Stekovic Christina Gleixner Christian Schmid Lisa Klug Alice G Sorgo Tobias Eisenberg Sabrina Büttner Guillermo Mariño Rafal Koziel Pidder Jansen-Dürr Kai-Uwe Fröhlich Guido Kroemer Frank Madeo |
| author_sort |
Christoph Ruckenstuhl |
| title |
Lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification. |
| title_short |
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_sort |
lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/2513812671d248ae85a0d77c88148d65 |
| work_keys_str_mv |
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| _version_ |
1718424466416992256 |