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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Molecular and Cellular Biology
2019
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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. |
format | Online Article Text |
id | pubmed-6449716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
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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