title: A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling.
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.
authors.affiliation: Max-Planck-Institut fuer Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Gerisch
authors.forename: Veerle
authors.initials: V
authors.lastname: Rottiers
authors.forename: Dongling
authors.initials: D
authors.lastname: Li
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Motola
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Cummins
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: David J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005854:Germ Cells / Q000187:drug effects; D007422:Intestines / Q000187:drug effects; D007447:Invertebrate Hormones / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects; D008024:Ligands; D008136:Longevity / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013696:Temperature
chemical_list: D001647:Bile Acids and Salts; D029742:Caenorhabditis elegans Proteins; D007447:Invertebrate Hormones; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D003577:Cytochrome P-450 Enzyme System; C486228:DAF-9 protein, C elegans