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Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models

Title
Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
Authors
Kuk, Myeong UkKim, Jae WonLee, Young-SamCho, Kyung A.Park, Joon TaePark, Sang Chul
DGIST Authors
Lee, Young-Sam
Issue Date
2019-03
Citation
Molecules and Cells, 42(3), 210-217
Type
Article
Article Type
Article
Author Keywords
ATM inhibitionHGPSKU-60019mitochondrial functionWS
Keywords
WERNER SYNDROME PROTEINMITOCHONDRIAL DYSFUNCTIONPROGERIACELLSLAMINLIPOFUSCINASSAY
ISSN
1016-8478
Abstract
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 agerelated disease.
URI
http://hdl.handle.net/20.500.11750/9683
DOI
10.14348/molcells.2018.0352
Publisher
한국분자세포생물학회
Related Researcher
  • Author Lee, Young-Sam Senescence-Associated Mechanism Lab
  • Research Interests DNA replication and repair; Restoration of cellular senescence; Structural and functional relationship of proteins
Files:
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Collection:
Department of New BiologySenescence-Associated Mechanism Lab1. Journal Articles


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