hide
Free keywords:
Adaptation, Physiological/drug effects
Animals
Bile Acids and Salts/*pharmacology
Caenorhabditis elegans/*drug effects/*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
Abstract:
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.
