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Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models

The maintenance of mitochondrial function is closely linked to the control of senescence. In our previous study, we uncovered a novel mechanism in which senescence amelioration in normal aging cells is mediated by the recovered mitochondrial function upon Ataxia telangiectasia mutated (ATM) inhibiti...

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Autores principales: Kuk, Myeong Uk, Kim, Jae Won, Lee, Young-Sam, Cho, Kyung A, Park, Joon Tae, Park, Sang Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449716/
https://www.ncbi.nlm.nih.gov/pubmed/30726661
http://dx.doi.org/10.14348/molcells.2018.0352
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author Kuk, Myeong Uk
Kim, Jae Won
Lee, Young-Sam
Cho, Kyung A
Park, Joon Tae
Park, Sang Chul
author_facet Kuk, Myeong Uk
Kim, Jae Won
Lee, Young-Sam
Cho, Kyung A
Park, Joon Tae
Park, Sang Chul
author_sort Kuk, Myeong Uk
collection PubMed
description The maintenance of mitochondrial function is closely linked to the control of senescence. In our previous study, we uncovered a novel mechanism in which senescence amelioration in normal aging cells is mediated by the recovered mitochondrial function upon Ataxia telangiectasia mutated (ATM) inhibition. However, it remains elusive whether this mechanism is also applicable to senescence amelioration in accelerated aging cells. In this study, we examined the role of ATM inhibition on mitochondrial function in Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) cells. We found that ATM inhibition induced mitochondrial functional recovery accompanied by metabolic reprogramming, which has been known to be a prerequisite for senescence alleviation in normal aging cells. Indeed, the induced mitochondrial metabolic reprogramming was coupled with senescence amelioration in accelerated aging cells. Furthermore, the therapeutic effect via ATM inhibition was observed in HGPS as evidenced by reduced progerin accumulation with concomitant decrease of abnormal nuclear morphology. Taken together, our data indicate that the mitochondrial functional recovery by ATM inhibition might represent a promising strategy to ameliorate the accelerated aging phenotypes and to treat age-related disease.
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spelling pubmed-64497162019-04-10 Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models Kuk, Myeong Uk Kim, Jae Won Lee, Young-Sam Cho, Kyung A Park, Joon Tae Park, Sang Chul Mol Cells Article The maintenance of mitochondrial function is closely linked to the control of senescence. In our previous study, we uncovered a novel mechanism in which senescence amelioration in normal aging cells is mediated by the recovered mitochondrial function upon Ataxia telangiectasia mutated (ATM) inhibition. However, it remains elusive whether this mechanism is also applicable to senescence amelioration in accelerated aging cells. In this study, we examined the role of ATM inhibition on mitochondrial function in Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) cells. We found that ATM inhibition induced mitochondrial functional recovery accompanied by metabolic reprogramming, which has been known to be a prerequisite for senescence alleviation in normal aging cells. Indeed, the induced mitochondrial metabolic reprogramming was coupled with senescence amelioration in accelerated aging cells. Furthermore, the therapeutic effect via ATM inhibition was observed in HGPS as evidenced by reduced progerin accumulation with concomitant decrease of abnormal nuclear morphology. Taken together, our data indicate that the mitochondrial functional recovery by ATM inhibition might represent a promising strategy to ameliorate the accelerated aging phenotypes and to treat age-related disease. Korean Society for Molecular and Cellular Biology 2019-03-31 2019-02-01 /pmc/articles/PMC6449716/ /pubmed/30726661 http://dx.doi.org/10.14348/molcells.2018.0352 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.
spellingShingle Article
Kuk, Myeong Uk
Kim, Jae Won
Lee, Young-Sam
Cho, Kyung A
Park, Joon Tae
Park, Sang Chul
Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
title Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
title_full Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
title_fullStr Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
title_full_unstemmed Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
title_short Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
title_sort alleviation of senescence via atm inhibition in accelerated aging models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449716/
https://www.ncbi.nlm.nih.gov/pubmed/30726661
http://dx.doi.org/10.14348/molcells.2018.0352
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