期刊
BIOFACTORS
卷 40, 期 2, 页码 247-257出版社
WILEY
DOI: 10.1002/biof.1146
关键词
FoxO3a; DAF-16; antioxidant; oxidant; ROS; C; elegans; PDK-1; SGK-1; oxidative stress; free radicals
资金
- Ministry of Education, Culture, Sports, Science and Technology
- Japanese Government Scholarship
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. (c) 2013 BioFactors, 40(2):247-257, 2014
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