The endogenous ligand Stunted of the GPCR Methuselah extends lifespan in Drosophila Academic Article uri icon


MeSH Major

  • Aging
  • Drosophila Proteins
  • Drosophila melanogaster
  • Longevity
  • Receptors, G-Protein-Coupled


  • Many extracellular signals are transmitted to the interior of the cell by receptors with seven membrane-spanning helices that trigger their effects by means of heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins). These G-protein-coupled receptors (GPCRs) control various physiological functions in evolution from pheromone-induced mating in yeast to cognition in humans. The potential role of the G-protein signalling system in the control of animal ageing has been highlighted by the genetic revelation that mutation of a GPCR encoded by methuselah extends the lifespan of adult Drosophila flies. How methuselah functions in controlling ageing is not clear. A first essential step towards the understanding of methuselah function is to determine the ligands of Methuselah. Here we report the identification and characterization of two endogenous peptide ligands of Methuselah, designated Stunted A and B. Flies with mutations in the gene encoding these ligands show an increase in lifespan and resistance to oxidative stress. We conclude that the Stunted-Methuselah system is involved in the control of animal ageing.

publication date

  • June 2004



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1038/ncb1133

PubMed ID

  • 15133470

Additional Document Info

start page

  • 540

end page

  • 6


  • 6


  • 6