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Effects of Thujaplicins on the Promoter Activities of the Human SIRT1 and Telomere Maintenance Factor Encoding Genes

Fumiaki Uchiumi, Haruki Tachibana, Hideaki Abe, Atsushi Yoshimori, Takanori Kamiya, Makoto Fujikawa, Steven Larsen, Shigeo Ebizuka and Sei-ichi Tanuma

Resveratrol (Rsv) has been shown to extend the lifespan of diverse range of species to activate sirtuin (SIRT) family proteins, which belong to the class III NAD+ dependent histone de-acetylases (HDACs).The protein deacetylating enzyme SIRT1 has been implicated in the regulation of cellular senescence and aging processes in mammalian cells. However, higher concentrations of this natural compound cause cell death. Therefore, novel compounds that have reduced cellular toxicity will be required for anti-aging therapy, especially for dermatological treatments. In this study, the Luciferase (Luc) expression vector pGL4-SIRT1 containing 396-bp of the 5’-upstream region of the human SIRT1 gene was transfected into HeLa S3 cells and Luc assay was performed. The results showed that treatments with the natural compound, α-, β- and γ-thujaplicins increase the SIRT1 promoter activity more than that with Rsv. Moreover, we carried out multiple transfection of Luc reporter vectors containing 5’-upstream regions of various human telomere maintenance factor encoding genes, and observed that β−thujaplicin (hinokitiol) activates TERT, RTEL, TRF1, DKC1, RAP1 (TERF2IP) and TPP1(ACD) promoters. These results suggest that that the β−thujaplicin could be used as anti-aging drugs to delay cellular senescence through activating SIRT1 transcription along with strengthening stability of telomeres.