MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.

Calorie restriction (CR) robustly extends the lifespan of numerous species. In the yeast Saccharomyces cerevisiae, CR has been proposed to extend lifespan by boosting the activity of sirtuin deacetylases, thereby suppressing the formation of toxic repetitive ribosomal DNA (rDNA) circles. An alternat...

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Autores principales:	Oliver Medvedik, Dudley W Lamming, Keyman D Kim, David A Sinclair
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/93989e7a876647aabaa90ca605f5e9bd
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spelling	oai:doaj.org-article:93989e7a876647aabaa90ca605f5e9bd2021-11-25T05:33:08ZMSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.1544-91731545-788510.1371/journal.pbio.0050261https://doaj.org/article/93989e7a876647aabaa90ca605f5e9bd2007-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.0050261https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Calorie restriction (CR) robustly extends the lifespan of numerous species. In the yeast Saccharomyces cerevisiae, CR has been proposed to extend lifespan by boosting the activity of sirtuin deacetylases, thereby suppressing the formation of toxic repetitive ribosomal DNA (rDNA) circles. An alternative theory is that CR works by suppressing the TOR (target of rapamycin) signaling pathway, which extends lifespan via mechanisms that are unknown but thought to be independent of sirtuins. Here we show that TOR inhibition extends lifespan by the same mechanism as CR: by increasing Sir2p activity and stabilizing the rDNA locus. Further, we show that rDNA stabilization and lifespan extension by both CR and TOR signaling is due to the relocalization of the transcription factors Msn2p and Msn4p from the cytoplasm to the nucleus, where they increase expression of the nicotinamidase gene PNC1. These findings suggest that TOR and sirtuins may be part of the same longevity pathway in higher organisms, and that they may promote genomic stability during aging.Oliver MedvedikDudley W LammingKeyman D KimDavid A SinclairPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 5, Iss 10, p e261 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Oliver Medvedik Dudley W Lamming Keyman D Kim David A Sinclair MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.
description	Calorie restriction (CR) robustly extends the lifespan of numerous species. In the yeast Saccharomyces cerevisiae, CR has been proposed to extend lifespan by boosting the activity of sirtuin deacetylases, thereby suppressing the formation of toxic repetitive ribosomal DNA (rDNA) circles. An alternative theory is that CR works by suppressing the TOR (target of rapamycin) signaling pathway, which extends lifespan via mechanisms that are unknown but thought to be independent of sirtuins. Here we show that TOR inhibition extends lifespan by the same mechanism as CR: by increasing Sir2p activity and stabilizing the rDNA locus. Further, we show that rDNA stabilization and lifespan extension by both CR and TOR signaling is due to the relocalization of the transcription factors Msn2p and Msn4p from the cytoplasm to the nucleus, where they increase expression of the nicotinamidase gene PNC1. These findings suggest that TOR and sirtuins may be part of the same longevity pathway in higher organisms, and that they may promote genomic stability during aging.
format	article
author	Oliver Medvedik Dudley W Lamming Keyman D Kim David A Sinclair
author_facet	Oliver Medvedik Dudley W Lamming Keyman D Kim David A Sinclair
author_sort	Oliver Medvedik
title	MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.
title_short	MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.
title_full	MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.
title_fullStr	MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.
title_full_unstemmed	MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.
title_sort	msn2 and msn4 link calorie restriction and tor to sirtuin-mediated lifespan extension in saccharomyces cerevisiae.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/93989e7a876647aabaa90ca605f5e9bd
work_keys_str_mv	AT olivermedvedik msn2andmsn4linkcalorierestrictionandtortosirtuinmediatedlifespanextensioninsaccharomycescerevisiae AT dudleywlamming msn2andmsn4linkcalorierestrictionandtortosirtuinmediatedlifespanextensioninsaccharomycescerevisiae AT keymandkim msn2andmsn4linkcalorierestrictionandtortosirtuinmediatedlifespanextensioninsaccharomycescerevisiae AT davidasinclair msn2andmsn4linkcalorierestrictionandtortosirtuinmediatedlifespanextensioninsaccharomycescerevisiae
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MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.

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