Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression

In yeast, chronological senescence (CS) is defined as loss of viability in stationary culture. Although its relevance to the organismal aging remained unclear, yeast CS was one of the most fruitful models in aging research. Here we described a mammalian replica of yeast CS: loss of viability of over...

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Main Authors:	Leontieva, Olga V., Blagosklonny, Mikhail V.
Format:	Online
Language:	English
Published:	Impact Journals LLC 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249453/

id	pubmed-3249453
recordtype	oai_dc
spelling	pubmed-32494532012-01-03 Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression Leontieva, Olga V. Blagosklonny, Mikhail V. Research Paper In yeast, chronological senescence (CS) is defined as loss of viability in stationary culture. Although its relevance to the organismal aging remained unclear, yeast CS was one of the most fruitful models in aging research. Here we described a mammalian replica of yeast CS: loss of viability of overgrown “yellow” cancer cell culture. In a density and time (chronological)-dependent manner, cell culture loses the ability to re-grow in fresh medium. Rapamycin dramatically decelerated CS. Loss of viability was caused by acidification of the medium by lactic acid (lactate). Rapamycin decreased production of lactate, making conditioned medium (CM) less deadly. Both deadly CM and lactate caused loss of viability in low cell density, not preventable by either rapamycin or additional glucose. Also, NAC, LY294002, U0126, GSK733, which all indirectly inhibit mTOR and have been shown to suppress the senescent phenotype in traditional models of mammalian cell senescence, also decreased lactate production and decelerated CS. We discuss that although CS does not mimic organismal aging, the same signal transduction pathways that drive CS also drive aging. Impact Journals LLC 2011-12-10 /pmc/articles/PMC3249453/ /pubmed/22156391 Text en Copyright: © 2011 Leontieva and Blagosklonny 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
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Leontieva, Olga V. Blagosklonny, Mikhail V.
spellingShingle	Leontieva, Olga V. Blagosklonny, Mikhail V. Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
author_facet	Leontieva, Olga V. Blagosklonny, Mikhail V.
author_sort	Leontieva, Olga V.
title	Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
title_short	Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
title_full	Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
title_fullStr	Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
title_full_unstemmed	Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
title_sort	yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
description	In yeast, chronological senescence (CS) is defined as loss of viability in stationary culture. Although its relevance to the organismal aging remained unclear, yeast CS was one of the most fruitful models in aging research. Here we described a mammalian replica of yeast CS: loss of viability of overgrown “yellow” cancer cell culture. In a density and time (chronological)-dependent manner, cell culture loses the ability to re-grow in fresh medium. Rapamycin dramatically decelerated CS. Loss of viability was caused by acidification of the medium by lactic acid (lactate). Rapamycin decreased production of lactate, making conditioned medium (CM) less deadly. Both deadly CM and lactate caused loss of viability in low cell density, not preventable by either rapamycin or additional glucose. Also, NAC, LY294002, U0126, GSK733, which all indirectly inhibit mTOR and have been shown to suppress the senescent phenotype in traditional models of mammalian cell senescence, also decreased lactate production and decelerated CS. We discuss that although CS does not mimic organismal aging, the same signal transduction pathways that drive CS also drive aging.
publisher	Impact Journals LLC
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249453/
_version_	1611497629802299392

Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression

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