A steroid hormone that extends the lifespan of Caenorhabditis elegans |
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Authors: | Broué Florence Liere Philippe Kenyon Cynthia Baulieu Etienne-Emile |
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Institution: | INSERM UMR788, 80 rue du Général Leclerc, 94276, Le Kremlin-Bicêtre, Cedex, France. |
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Abstract: | 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. |
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Keywords: | C elegans DAF-12 (nuclear receptor) DAF-9 (CYP-450) germ cell ablation lifespan pregnenolone steroids |
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