Vorinostat Induces Cellular Senescence in Fibroblasts Derived from Young and Aged Dogs

다국어 초록 (Multilingual Abstract)

Although HDACIs affect ubiquitously expressed histone deacetylase and increase cellular senescence, therehas been little study on the effect of age on treatment with HDACIs. Accordingly, the purpose of this study wasto compare cellular senescence status and vorinostat-induced senescence in fibroblasts derived from aged dogs comparedto young dogs. Skin tissues were taken from young (1-year-old) and aged (7-year-old) male dogs, and fibroblasts werecultured without (control) or with 10 uM of vorinostat for 24 hr. Beta-galactosidase activity was assessed, and realtimepolymerase chain reaction and western blotting were performed to analyze the expression levels of transcriptsand proteins related to cellular senescence. Beta-galactosidase activity was higher in aged dogs compared to youngdogs in the control group, and was increased by vorinostat treatment. Expression of p21, p53 and p16 transcripts washigher in the aged than in the young group, and all transcripts were affected by vorinostat in both young and agedgroups. Western blot results showed lower H3K9 acetylation in the aged dogs compared to the young dogs, and theacetylation was increased by vorinostat treatment in both groups. However, there was no significant difference betweenthe transcript or protein alterations induced by vorinostat.

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