A DAF-16/FoxO3a-dependent longevity signal is initiated by antioxidants

Authors

  • Juewon Kim,

    1. Bioscience Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea
    2. Department of Integrated Biosciences, University of Tokyo, Chiba, Japan
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  • Naoko Ishihara,

    1. Department of Integrated Biosciences, University of Tokyo, Chiba, Japan
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  • Tae Ryong Lee

    Corresponding author
    1. Bioscience Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea
    • Address for correspondence: Tae Ryong Lee, Ph. D., Bioscience Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446–729, Republic of Korea. Tel.: +82-31-280–5850; Fax: +82-31-899–2595; E-mail: TRLee@amorepacific.com.

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Abstract

The precise mechanisms of antioxidant-mediated longevity are poorly understood. We show that an antioxidant treatment can extend the lifespan of Caenorhabditis elegans (C. elegans) through the nuclear translocation of the forkhead box O transcription factor (FoxO) homolog DAF-16. This pathway was found to involve 3-phosphoinositide-dependent kinase-1 (PDK-1) and serum- and glucocorticoid-regulated kinase-1 (SGK-1), distinct from the known oxidative stress-mediated mechanism in which FoxO3a translocation is regulated by c-Jun N-terminal kinase (JNK) and mammalian sterile 20-like kinase-1 (MST-1). The differences in the mechanisms of FoxO activation by antioxidants and oxidants result in differences in FoxO phosphorylation and target gene expression. Based on these results, we found that a combination of early antioxidant treatment and late oxidant treatment is most effective for lifespan extension in C. elegans. © 2013 BioFactors, 40(2):247–257, 2014

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