The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1

Juewon Kim, Young Gyu Kang, Jee young Lee, Dong hwa Choi, Young uk Cho, Jae Min Shin, Jun Seong Park, John Hwan Lee, Wan Gi Kim, Dae Bang Seo, Tae Ryong Lee, Yusei Miyamoto, Kyoung Tai No

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Abstract

Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid of confers, such as pinus species (P. densiflora, P. sylvestris) and grand fir (Abies grandis), and it induces various biological actions including antimicrobial, antiulcer, and cardiovascular activities. The cellular targets that mediate these actions are largely unknown yet. In this report, we suggest that DAA is an anti-aging reagent. DAA has lifespan extension effects in Caenorhabditis elegans, prevents lipofuscin accumulation, and prevents collagen secretion in human dermal fibroblasts. We found that these anti-aging effects are primarily mediated by SIRT1 activation. Lifespan extension effects by DAA were ameliorated in sir-2.1 mutants and SIRT1 protein expression was increased, resulting in the deacetylation of SIRT1 target protein PGC-1α. Moreover, DAA binds directly to the SIRT1 protein independent of the SIRT1 substrate NAD+ levels. Through a molecular docking study, we also propose a binding model for DAA-SIRT1. Taken together, our results demonstrate that the anti-aging effects are the first identified biological property of DAA and that the direct activation of SIRT1 enzymatic activity suggests the potential use of this natural diterpene, or related compounds, in age-related diseases or as a preventive reagent against the aging process.

Original languageEnglish
Pages (from-to)216-225
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume412
DOIs
Publication statusPublished - 2015 Sep 5

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Kim, J., Kang, Y. G., Lee, J. Y., Choi, D. H., Cho, Y. U., Shin, J. M., Park, J. S., Lee, J. H., Kim, W. G., Seo, D. B., Lee, T. R., Miyamoto, Y., & No, K. T. (2015). The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1. Molecular and Cellular Endocrinology, 412, 216-225. https://doi.org/10.1016/j.mce.2015.05.006