A steroid hormone that extends the lifespan of Caenorhabditis elegans.

Authors: Broué F; Liere P; Kenyon C; Baulieu EE

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.

Keywords: Animals; Caenorhabditis elegans/drug effects/genetics/*metabolism; Caenorhabditis elegans Proteins/genetics/metabolism; Cytochrome P-450 Enzyme System/genetics/metabolism; Gene Expression Regulation, Developmental/genetics; Germ Cells/cytology/*metabolism; Gonadal Steroid Hormones/metabolism/*pharmacology; Longevity/*drug effects/genetics; Mutation/genetics; Pregnenolone/metabolism/*pharmacology; Receptors, Cytoplasmic and Nuclear/genetics/metabolism; Reproduction/physiology
Journal: Aging cell
Volume: 6
Issue: 1
Pages: 87-94
Date: Feb. 3, 2007
PMID: 17266678
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Citation:

Broué F, Liere P, Kenyon C, Baulieu EE (2007) A steroid hormone that extends the lifespan of Caenorhabditis elegans. Aging cell 6: 87-94.


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