Mol. Cells 2019; 42():   https://doi.org/10.14348/molcells.2018.0352
Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
Myeong Uk Kuk1,6, Jae Won Kim1,6, Young-Sam Lee2,3, Kyung A Cho4, Joon Tae Park1,*, and Sang Chul Park2,5,*
1Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, Korea, 2Well Aging Research Center, 3Department of New Biology, DGIST, Daegu, Korea, 4Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea, 5The Future Life & Society Research Center, Chonnam National University, Gwangju, Korea, 6These authors contributed equally to this work.
*Correspondence: joontae.park@inu.ac.kr (JTP); scpark@snu.ac.kr (SCP)
Received August 20, 2018; Revised January 2, 2019; Accepted January 7, 2019.; Published online February 1, 2019.
© 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/).
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.
Keywords: ATM inhibition, HGPS, KU-60019, mitochondrial function, WS

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31 January 2019 Volume 42,
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