Larval crowding accelerates C. elegans development and reduces lifespan

• Published in: PLoS genetics 2017-04, Vol.13 (4), p.e1006717-e1006717
• Main Authors: Ludewig, Andreas H, Gimond, Clotilde, Judkins, Joshua C, Thornton, Staci, Pulido, Dania C, Micikas, Robert J, Döring, Frank, Antebi, Adam, Braendle, Christian, Schroeder, Frank C
• Format: Article
• Language: English
• Subjects: Adults; Aging; Animal development; Animals; Biology; Biology and Life Sciences; Biosynthesis; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans Proteins - biosynthesis; Caenorhabditis elegans Proteins - genetics; Chemistry; Chemoreception; Crowding; Diapause; Egg laying; Environmental conditions; Evolution & development; Fatty Acids - metabolism; Food science; Gene Expression Regulation, Developmental; Genetic aspects; Hermaphrodites; Hermaphroditic Organisms - genetics; Hermaphroditic Organisms - growth & development; Hormones; Larva - genetics; Larva - growth & development; Life span; Life span (Biology); Ligands; Longevity; Longevity - genetics; Nematodes; Neuropeptides - metabolism; Nutrition; Oxidation; Pediatrics; People and Places; Pheromones; Physiological aspects; Population Density; Puberty; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - genetics; Research and Analysis Methods; Signal Transduction; Steroid hormones; Worms
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006717

Environmental conditions experienced during animal development are thought to have sustained impact on maturation and adult lifespan. Here we show that in the model organism C. elegans developmental rate and adult lifespan depend on larval population density, and that this effect is mediated by excreted small molecules. By using the time point of first egg laying as a marker for full maturity, we found that wildtype hermaphrodites raised under high density conditions developed significantly faster than animals raised in isolation. Population density-dependent acceleration of development (Pdda) was dramatically enhanced in fatty acid β-oxidation mutants that are defective in the biosynthesis of ascarosides, small-molecule signals that induce developmental diapause. In contrast, Pdda is abolished by synthetic ascarosides and steroidal ligands of the nuclear hormone receptor DAF-12. We show that neither ascarosides nor any known steroid hormones are required for Pdda and that another chemical signal mediates this phenotype, in part via the nuclear hormone receptor NHR-8. Our results demonstrate that C. elegans development is regulated by a push-pull mechanism, based on two antagonistic chemical signals: chemosensation of ascarosides slows down development, whereas population-density dependent accumulation of a different chemical signal accelerates development. We further show that the effects of high larval population density persist through adulthood, as C. elegans larvae raised at high densities exhibit significantly reduced adult lifespan and respond differently to exogenous chemical signals compared to larvae raised at low densities, independent of density during adulthood. Our results demonstrate how inter-organismal signaling during development regulates reproductive maturation and longevity.