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Nat Chem Biol

Title:		An excreted small molecule promotes C. elegans reproductive development and aging
Author(s):		Ludewig AH; Artyukhin AB; Aprison EZ; Rodrigues PR; Pulido DC; Burkhardt RN; Panda O; Zhang YK; Gudibanda P; Ruvinsky I; Schroeder FC;
Address:		"Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA. Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA. Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA. ilya.ruvinsky@northwestern.edu. Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA. fs31@cornell.edu"
Journal Title:		Nat Chem Biol
Year:		2019
Volume:		20190718
Issue:		8
Page Number:		838 - 845
DOI:		10.1038/s41589-019-0321-7
ISSN/ISBN:		1552-4469 (Electronic) 1552-4450 (Print) 1552-4450 (Linking)
Abstract:		"Excreted small-molecule signals can bias developmental trajectories and physiology in diverse animal species. However, the chemical identity of these signals remains largely obscure. Here we report identification of an unusual N-acylated glutamine derivative, nacq#1, that accelerates reproductive development and shortens lifespan in Caenorhabditis elegans. Produced predominantly by C. elegans males, nacq#1 hastens onset of sexual maturity in hermaphrodites by promoting exit from the larval dauer diapause and by accelerating late larval development. Even at picomolar concentrations, nacq#1 shortens hermaphrodite lifespan, suggesting a trade-off between reproductive investment and longevity. Acceleration of development by nacq#1 requires chemosensation and is dependent on three homologs of vertebrate steroid hormone receptors. Unlike ascaroside pheromones, which are restricted to nematodes, fatty acylated amino acid derivatives similar to nacq#1 have been reported from humans and invertebrates, suggesting that related compounds may serve signaling functions throughout metazoa"
Keywords:		"Aging/*physiology Animals Caenorhabditis elegans/*metabolism Caenorhabditis elegans Proteins/metabolism Gene Expression Regulation, Developmental/physiology Hermaphroditic Organisms/physiology Male Mutation Oviposition/*physiology Signal Transduction;"
Notes:		"MedlineLudewig, Andreas H Artyukhin, Alexander B Aprison, Erin Z Rodrigues, Pedro R Pulido, Dania C Burkhardt, Russell N Panda, Oishika Zhang, Ying K Gudibanda, Pooja Ruvinsky, Ilya Schroeder, Frank C eng R01 GM126125/GM/NIGMS NIH HHS/ R01 GM113692/GM/NIGMS NIH HHS/ T32 GM008500/GM/NIGMS NIH HHS/ R35 GM131877/GM/NIGMS NIH HHS/ R01 GM088290/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. 2019/07/20 Nat Chem Biol. 2019 Aug; 15(8):838-845. doi: 10.1038/s41589-019-0321-7. Epub 2019 Jul 18"