A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling

Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5014-9. doi: 10.1073/pnas.0700847104. Epub 2007 Mar 14.


Broad aspects of Caenorhabditis elegans life history, including larval developmental timing, arrest at the dauer diapause, and longevity, are regulated by the nuclear receptor DAF-12. Endogenous DAF-12 ligands are 3-keto bile acid-like steroids, called dafachronic acids, which rescue larval defects of hormone-deficient mutants, such as daf-9/cytochrome P450 and daf-36/Rieske oxygenase, and activate DAF-12. Here we examined the effect of dafachronic acid on pathways controlling lifespan. Dafachronic acid supplementation shortened the lifespan of long-lived daf-9 mutants and abolished their stress resistance, indicating that the ligand is "proaging" in response to signals from the dauer pathways. However, the ligand extended the lifespan of germ-line ablated daf-9 and daf-36 mutants, showing that it is "antiaging" in the germ-line longevity pathway. Thus, dafachronic acid regulates C. elegans lifespan according to signaling state. These studies provide key evidence that bile acid-like steroids modulate aging in animals.

Publication types

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

MeSH terms

  • Adaptation, Physiological / drug effects
  • Animals
  • Bile Acids and Salts / pharmacology*
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Nucleus / drug effects
  • Cytochrome P-450 Enzyme System / metabolism
  • Germ Cells / drug effects
  • Intestines / drug effects
  • Invertebrate Hormones / pharmacology*
  • Larva / drug effects
  • Ligands
  • Longevity / drug effects*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / drug effects*
  • Temperature


  • Bile Acids and Salts
  • Caenorhabditis elegans Proteins
  • Invertebrate Hormones
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Cytochrome P-450 Enzyme System
  • DAF-9 protein, C elegans