Royalactin extends lifespan of Caenorhabditis elegans through epidermal growth factor signaling

Exp Gerontol. 2014 Dec:60:129-35. doi: 10.1016/j.exger.2014.09.021. Epub 2014 Oct 16.


Royalactin is a glycoprotein essential for the development of long-lived queen honeybees. Only larvae fed with royal jelly, containing royalactin, develop into queens. Royalactin plays a central role in this process by switching on the epidermal growth factor (EGF) receptor signaling pathway which ultimately leads to epigenetic changes and a long-lived queen phenotype. Recently it was shown that royalactin by itself also extends lifespan in Drosophila melanogaster. Yet, the mechanism by which royalactin promotes longevity remains largely unknown. We set out to characterize the effects of royalactin on Caenorhabditis elegans lifespan, and clarify the possible involvement of EGF signaling in this process. We demonstrate that royalactin extends lifespan of this nematode and that both EGF (LIN-3) and its receptor (LET-23) are essential to this process. To our knowledge, this is the first report of royalactin-mediated lifespan extension in a non-insect species. Additionally, we show that royalactin enhances locomotion in adult nematodes, implying that royalactin also influences healthspan. Our results suggest that royalactin is an important lifespan-extending factor in royal jelly and acts by promoting EGF signaling in C. elegans. Further work will now be needed to clarify which (secondary) signaling pathways are activated by royalactin, and how this ultimately translates into an extended health- and lifespan.

Keywords: Aging; Dietary intervention; EGF signaling; Healthspan; Invertebrate; Royal jelly.

Publication types

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

MeSH terms

  • Aging / physiology
  • Animals
  • Bees / physiology
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Epidermal Growth Factor / antagonists & inhibitors
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / physiology*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology
  • Fatty Acids / physiology
  • Gene Knockdown Techniques
  • Genes, Helminth
  • Glycoproteins / chemistry
  • Glycoproteins / pharmacology*
  • Glycoproteins / physiology
  • Insect Proteins / chemistry
  • Insect Proteins / pharmacology*
  • Insect Proteins / physiology
  • Locomotion / drug effects
  • Longevity / drug effects*
  • Longevity / genetics
  • Longevity / physiology*
  • Signal Transduction / drug effects


  • Caenorhabditis elegans Proteins
  • Fatty Acids
  • Glycoproteins
  • Insect Proteins
  • MRJP1 protein, Apis mellifera
  • Lin-3 protein, C elegans
  • Epidermal Growth Factor
  • ErbB Receptors
  • let-23 protein, C elegans
  • royal jelly