title: The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1.
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.
authors.affiliation: Beauty Food Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea; Department of Integrated Biosciences, University of Tokyo, Chiba 277-8562, Japan. Electronic address: jwkim@amorepacific.com.
authors.forename: Juewon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Skin Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Young-Gyu
authors.initials: YG
authors.lastname: Kang
authors.affiliation: Bioinformatics & Molecular Design Research Center, Yonsei Engineering Research Park, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Jee-young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Gyeonggi Bio Center, Gyeonggi Institute of Science & Technology Promotion, Suwon-si, Gyeonggi-do 443-270, Republic of Korea.
authors.forename: Dong-hwa
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Skin care Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Young-uk
authors.initials: YU
authors.lastname: Cho
authors.affiliation: Bioinformatics & Molecular Design Research Center, Yonsei Engineering Research Park, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Skin Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Jun Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Skin Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: John Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Beauty Food Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Wan Gi
authors.initials: WG
authors.lastname: Kim
authors.affiliation: Beauty Food Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Dae Bang
authors.initials: DB
authors.lastname: Seo
authors.affiliation: Bioscience Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
authors.affiliation: Department of Integrated Biosciences, University of Tokyo, Chiba 277-8562, Japan. Electronic address: yusei74@k.u-tokyo.ac.jp.
authors.forename: Yusei
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Bioinformatics & Molecular Design Research Center, Yonsei Engineering Research Park, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea; Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea. Electronic address: ktno@yonsei.ac.kr.
authors.forename: Kyoung Tai
authors.initials: KT
authors.lastname: No
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology*; D000328:Adult; D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D002478:Cells, Cultured; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D011485:Protein Binding; D000077185:Resveratrol; D037761:Sirtuins / Q000737:chemistry / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D045784:Abietanes; D029742:Caenorhabditis elegans Proteins; D020536:Enzyme Activators; D013267:Stilbenes; C013913:dehydroabietic acid; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins; D000077185:Resveratrol
keywords: Binding model; Dehydroabietic acid; Longevity; Phytochemical; SIRT1