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

Experimental Gerontology
Joon Tae ParkSang Chul Park

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 trea...Continue Reading

Citations

Jul 4, 2019·PloS One·Juliana Carvalhães Lago, Maria Beatriz Puzzi
May 10, 2018·Bioscience Reports·Yukimasa TakedaPing Dai
Feb 23, 2020·Experimental & Molecular Medicine·Yohan KimDongho Choi
Oct 22, 2020·Clinical Science·Kaj E C BloklandJanette K Burgess
Aug 20, 2019·Experimental Gerontology·Jae Won KimJoon Tae Park
Jan 15, 2019·Biochemical and Biophysical Research Communications·Stefanie KiderlenStefanie Sudhop
Jun 24, 2020·Drug Discovery Today·Christos ErmogenousJanet M Lord

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