Alleviation of senescence via ATM inhibition in accelerated aging models

Myeong Uk Kuk, Jae Won Kim, Young Sam Lee, Kyung A. Cho, Joon Tae Park, Sang Chul Park

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 age-related disease.

Original languageEnglish
Pages (from-to)210-217
Number of pages8
JournalMolecules and Cells
Volume42
Issue number3
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© The Korean Society for Molecular and Cellular Biology. All rights reserved.

Keywords

  • ATM inhibition
  • HGPS
  • KU-60019
  • Mitochondrial function
  • WS

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