title: Larval crowding accelerates C. elegans development and reduces lifespan.
abstract: 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.
authors.affiliation: Molecular Prevention Group, Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.|Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, United States of Ameirca.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Ludewig
authors.affiliation: Institut de Biologie Valrose, CNRS, UMR7277, Parc Valrose, Nice, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Gimond
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, United States of Ameirca.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Judkins
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, United States of Ameirca.
authors.forename: Staci
authors.initials: S
authors.lastname: Thornton
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, United States of Ameirca.
authors.forename: Dania C
authors.initials: DC
authors.lastname: Pulido
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, United States of Ameirca.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Micikas
authors.affiliation: Molecular Prevention Group, Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
authors.affiliation: Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
authors.affiliation: Institut de Biologie Valrose, CNRS, UMR7277, Parc Valrose, Nice, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Braendle
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, United States of Ameirca.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D005227:Fatty Acids / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057850:Hermaphroditic Organisms / Q000235:genetics / Q000254:growth & development; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008136:Longevity / Q000235:genetics*; D009479:Neuropeptides / Q000378:metabolism; D011156:Population Density; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D009479:Neuropeptides; D018160:Receptors, Cytoplasmic and Nuclear; C410905:DAF-12 protein, C elegans; C439299:nhr-8 protein, C elegans; C075027:diapause hormone