期刊
EXPERIMENTAL GERONTOLOGY
卷 106, 期 -, 页码 8-15出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2018.02.012
关键词
Y-27632; Fasudil; ROCK inhibition; Senescence; Chromatin remodeling genes; Wound healing
资金
- Incheon National University research grant [2017-0385]
- DGIST R&D Program of the Ministry of Science, ICT and Technology of KOREA [2017010072, 2017010115]
- Chonnam National University R&D Program Grant for Research Chair Professor [2018-01]
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.
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