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A crucial role of ROCK for alleviation of senescence-associated phenotype
- A crucial role of ROCK for alleviation of senescence-associated phenotype
- Park, J.T.; Kang, H.T.; Park, C.H.; Lee, Young Sam; Cho, K.A.; Park, Sang Chul
- DGIST Authors
- Lee, Young Sam
- Issue Date
- Experimental Gerontology, 106, 8-15
- Article Type
- Y-27632; Fasudil; ROCK Inhibition; Senescence; Chromatin Remodeling; Genes; Wound Healing; DNA-damage Response; Cellular Senescence; Rho-kinase; Human Fibroblasts; Human-cells; Life-span; in-vivo; Mitochondria; Modulation; Lipofuscin; Chromatin Remodeling Genes
- 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.
- Elsevier Inc.
- Related Researcher
Lab of genome maintenance
DNA replication and repair; Restoration of cellular senescence; Structural and functional relationship of proteins
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- Department of New BiologyLab of Genome Maintenance1. Journal Articles
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