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Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16
Institute of Agricultural and Nutritional Sciences, Faculty III, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22 (Biozentrum), 06120 Halle/Saale, Germany
Institute of Toxicology, Heinrich-Heine-Universität Düsseldorf, P.O. Box 101007, 40001 Düsseldorf, Germany
Global Drug Development, Safety and Pharmacokinetics, Bayer Animal Health GmbH, Bayer HealthCare, Building 6700 Monheim, 51368 Leverkusen, Germany
* Author to whom correspondence should be addressed.
Received: 26 April 2013; in revised form: 16 May 2013 / Accepted: 17 May 2013 / Published: 4 June 2013
Abstract: Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue) and SKN-1 (Nrf2 homologue), which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS) detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038). Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid.
Keywords: C. elegans; daf-16; flavonoid; lifespan; myricetin; insulin-like signalling; oxidative stress; SKN-1
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MDPI and ACS Style
Büchter, C.; Ackermann, D.; Havermann, S.; Honnen, S.; Chovolou, Y.; Fritz, G.; Kampkötter, A.; Wätjen, W. Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16. Int. J. Mol. Sci. 2013, 14, 11895-11914.
Büchter C, Ackermann D, Havermann S, Honnen S, Chovolou Y, Fritz G, Kampkötter A, Wätjen W. Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16. International Journal of Molecular Sciences. 2013; 14(6):11895-11914.
Büchter, Christian; Ackermann, Daniela; Havermann, Susannah; Honnen, Sebastian; Chovolou, Yvonni; Fritz, Gerhard; Kampkötter, Andreas; Wätjen, Wim. 2013. "Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16." Int. J. Mol. Sci. 14, no. 6: 11895-11914.