Planta Med 2014; 80 - P2P1
DOI: 10.1055/s-0034-1394839

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

YG Kang 1, et al
  • 1R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446 – 729, Republic of Korea; Bioinformatics & Molecular Design Research Center, Yonsei Engineering Research Park, Yonsei University, Seodaemun-gu, Seoul 120 – 749, Republic of Korea

Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid of conifer species, such as Pinus species (P. densiflora, P. sylvestris) and grand fir (A. grandis), and it induces various biological actions including antimicrobial, antiulcer and cardiovascular activities. However, the anti-aging effect of DAA has not yet been examined. This study was designed to investigate anti-aging effects of DAA using aging model animal, Caenorhabditis elegans (C. elegans) and human dermal fibroblasts. DAA has lifespan extension effects in C. elegans. Additionally, DAA prevents lipofuscin accumulation and collagen decomposition in human dermal fibroblasts. We discovered 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 and-SIRT1. In Summary, our results indicate that DAA has anti-aging effect through direct activation of SIRT1. Therefore, we suggest that DAA, or related compounds could be applicable for age-related diseases or as a reagent against the skin-aging process.

Keywords: Dehydroabietic acid, Sirt-1, lipofuscin

References:

[1] Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410: 227 – 230.

[2] Brunk UT, Terman A (2002) Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med 33: 611 – 619.

[3] Sinclair DA, Guarente L (2014) Small-molecule allosteric activators of sirtuins. Annu Rev Pharmacol Toxicol 54: 18.1 – 18.18.