A steroid hormone that extends the lifespan of Caenorhabditis elegans.
Removing the germline of Caenorhabditis elegans extends lifespan. This lifespan extension requires the nuclear receptor DAF-12 and the cytochrome P450 DAF-9, suggesting that a lipophilic hormone is involved. Here we show that C. elegans contains several hormonal steroids that are also present in humans, including pregnenolone (3beta-hydroxy-pregn-5-en-20-one; PREG) and other pregnane and androstane derivatives. We find that PREG can extend the lifespan of C. elegans. Moreover, PREG levels rise when the germline is removed in a daf-9-dependent fashion. PREG extends the lifespan of germline-defective daf-9 mutants dramatically, but has no effect on daf-12 mutants. Thus, germline removal may extend lifespan, at least in part, by stimulating the synthesis of PREG.
Broué
Florence
F
INSERM UMR788, 80 rue du Général Leclerc, 94276, Le Kremlin-Bicêtre, Cedex, France.
Liere
Philippe
P
Kenyon
Cynthia
C
Baulieu
Etienne-Emile
EE
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000378:metabolism / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011284:Pregnenolone / Q000378:metabolism / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D012739:Gonadal Steroid Hormones; D018160:Receptors, Cytoplasmic and Nuclear; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; C486228:DAF-9 protein, C elegans