Myricetin-mediated lifespan extension in Caenorhabditis elegans is modulated by DAF-16

Int J Mol Sci. 2013 Jun 4;14(6):11895-914. doi: 10.3390/ijms140611895.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Caloric Restriction
  • Cell-Free System
  • Chromans
  • DNA-Binding Proteins / metabolism
  • Flavonoids / chemistry
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Forkhead Transcription Factors / metabolism*
  • Free Radical Scavengers / pharmacology
  • Green Fluorescent Proteins / metabolism
  • HCT116 Cells
  • Hot Temperature
  • Humans
  • Lipofuscin / metabolism
  • Longevity / drug effects*
  • Oxidation-Reduction / drug effects
  • Protein Transport / drug effects
  • Reactive Oxygen Species / metabolism
  • Stress, Physiological / drug effects
  • Transcription Factors / metabolism


  • Antioxidants
  • Caenorhabditis elegans Proteins
  • Chromans
  • DNA-Binding Proteins
  • Flavonoids
  • Forkhead Transcription Factors
  • Free Radical Scavengers
  • Lipofuscin
  • Reactive Oxygen Species
  • Transcription Factors
  • daf-16 protein, C elegans
  • Green Fluorescent Proteins
  • skn-1 protein, C elegans
  • myricetin
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid