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Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models
- 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
- DGIST Authors
- Lee, Young-Sam
- Issue Date
- Molecules and Cells, 42(3), 210-217
- Article Type
- Author Keywords
- ATM inhibition; HGPS; KU-60019; mitochondrial function; WS
- WERNER SYNDROME PROTEIN; MITOCHONDRIAL DYSFUNCTION; PROGERIA; CELLS; LAMIN; LIPOFUSCIN; ASSAY
- 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.
- Related Researcher
Senescence-Associated Mechanism Lab
DNA replication and repair; Restoration of cellular senescence; Structural and functional relationship of proteins
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- Department of New BiologySenescence-Associated Mechanism Lab1. Journal Articles
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