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A crucial role of ROCK for alleviation of senescence-associated phenotype

Title
A crucial role of ROCK for alleviation of senescence-associated phenotype
Authors
Park, J.T.Kang, H.T.Park, C.H.Lee, Young SamCho, K.A.Park, Sang Chul
DGIST Authors
Lee, Young Sam
Issue Date
2018-06
Citation
Experimental Gerontology, 106, 8-15
Type
Article
Article Type
Article
Keywords
Y-27632FasudilROCK InhibitionSenescenceChromatin RemodelingGenesWound HealingDNA-damage ResponseCellular SenescenceRho-kinaseHuman FibroblastsHuman-cellsLife-spanin-vivoMitochondriaModulationLipofuscinChromatin Remodeling Genes
ISSN
0531-5565
Abstract
In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. We found that ROCK inhibition induced the functional recovery of the mitochondria as well as the metabolic reprogramming, which are two salient features that are altered in normal aging cells. Moreover, microarray analysis revealed that the up-regulated pathway upon ROCK inhibition is enriched for chromatin remodeling genes, which may play an important role in the alleviation of senescence-associated cell cycle arrest. Indeed, ROCK inhibition induced cellular proliferation, concomitant with the amelioration of senescent phenotype. Furthermore, the restorative effect by ROCK inhibition was observed in vivo as evidenced by the facilitated cutaneous wound healing. Taken together, our data indicate that ROCK inhibition might be utilized to ameliorate normal aging process and to treat age-related disease. © 2018 Elsevier Inc.
URI
http://hdl.handle.net/20.500.11750/8985
DOI
10.1016/j.exger.2018.02.012
Publisher
Elsevier Inc.
Related Researcher
  • Author Lee, Young-Sam Lab of genome maintenance
  • 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 BiologyLab of Genome Maintenance1. Journal Articles


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