title: A DAF-16/FoxO3a-dependent longevity signal is initiated by antioxidants.
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.
authors.affiliation: Bioscience Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea; Department of Integrated Biosciences, University of Tokyo, Chiba, Japan.
authors.forename: Juewon
authors.initials: J
authors.lastname: Kim
authors.forename: Naoko
authors.initials: N
authors.lastname: Ishihara
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008136:Longevity; D053768:Metal Nanoparticles; D010984:Platinum / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D002839:Chromans; D003497:Cyclic N-Oxides; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; C108831:daf-16 protein, C elegans; C029217:phenyl-N-tert-butylnitrone; D010984:Platinum; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
keywords: C. elegans; FoxO3a/DAF-16; PDK-1; ROS; SGK-1; antioxidant; free radicals; oxidant; oxidative stress