Identification of a small molecule activator of SIRT1 gene expression

Si Young Cho, Miook Cho, Dae Bang Seo, Sang Jun Lee, Yousin Suh

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Increased SIRT1 expression exerts beneficial effects in transgenic animal models, ameliorating the onset and progression of aging-related disease phenotypes in various organs including the heart. The potential beneficial effects of SIRT1 have made SIRT1 a prime therapeutic target for age-related diseases and considerable efforts led to the identification of small molecule activator of SIRT1 protein. Thus far, however, a small molecule activator of SIRT1 gene expression has not been reported. Here, we report that syringaresinol, isolated from Panax ginseng berry pulp, is an activator of SIRT1 gene expression. Using human umbilical endothelial cells (HUVECs), we show that syringaresinol treatment induced binding of FOXO3 to the SIRT1 promoter in a sequence-specific manner, leading to induction of SIRT1 expression. Increased SIRT1 expression in HUVECs by syringaresinol treatment delayed cellular senescence and improved various markers of endothelial functions in a FOXO3 dependent manner. Collectively, these findings bring to light a new transcription activator of SIRT1 that may have therapeutic potential.

Original languageEnglish (US)
Pages (from-to)174-182
Number of pages9
JournalAging
Volume5
Issue number3
DOIs
StatePublished - Mar 2013

Keywords

  • Gene expression
  • SIRT1
  • Senescence
  • Small molecule activator
  • Syringaresinol

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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  • Cite this

    Cho, S. Y., Cho, M., Seo, D. B., Lee, S. J., & Suh, Y. (2013). Identification of a small molecule activator of SIRT1 gene expression. Aging, 5(3), 174-182. https://doi.org/10.18632/aging.100539