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KMID : 0578320190420030210
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Molecules and Cells
2019 Volume.42 No. 3 p.210 ~ p.217
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Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
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Kuk Myeong-Uk
Kim Jae-Won
Lee Young-Sam
Cho Kyung-A
Park Joon-Tae
Park Sang-Chul
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Abstract
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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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KEYWORD
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ATM inhibition, HGPS, KU-60019, mitochondrial function, WS
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