Fecundity and lifespan manipulations in Caenorhabditis elegans using exogenous peptides

Abstract

In this study using Caenorhabditis elegans, we have been able to suppress (> 60%) and enhance (> 40%) fecundity (number of offspring) while extending lifespan by a fifth, by administering synthetic peptides to the aqueous medium in which the nematodes were maintained. Untreated control adults fed live bacteria had significantly more offspring (17 vs 10 larvae each) than those fed dead bacteria. Average lifespan and time for 50% of the worms to die were the same at approximately 10 days, but there was a significant difference in terms of 100% mortality (28 vs 19 days). A reduction in fecundity of 30-40% occurred when a 14-mer peptide, EPL030, was administered to the worms' aqueous medium. The effect was dose-dependent across the range 0.1-10 mu M day(-1) of medium, but since the worms were fed live bacteria interpretation was problematic: was the effect direct or indirect? However, the anti-fecundity effect was reproduced in worms fed dead bacteria, when the test compound was administered at I mu M day(-1) of aqueous medium. The mean number of larvae produced in three groups: untreated controls, EPL030 and EPL001 (an anagrammatical version of EPL030 used as a comparator), were, respectively, 17, 6 (-64%) and 24 (+43%). Average lifespans were 8.7, 10.7 (+23%) and 10.3 days (+18%). Fluorescence localisation studies using a close analogue of the fecundity-suppressing EPL030 revealed a distribution that was generalised and uninformative. The fecundity-enhancing EPL001 concentrated in the genital tract. Caenorhabditis elegans is a potentially useful testbed for fecundity and lifespan studies using exogenous agents. The use of an aqueous medium and dead bacteria as food simplifies both the protocol and interpretation of results.