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.
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The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files.
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This work was supported in part by National Institutes of Health grants R01GM113692 (to F.C.S.), R01GM088290 (to F.C.S.) and T32GM008500 (to R.N.B.), R01GM126125 (to I.R.), and by National Science Foundation (NSF) grants IOS-1708518 and IOS-1755244 (to I.R.). F.C.S. is a faculty scholar of the Howard Hughes Medical Institute. This work made use of the Cornell University NMR Facility, which is supported, in part, by the NSF through MRI award CHE-1531632. We thank N. Movahed and D. Kiemle for assistance with MS and NMR spectroscopy and R. Smith and G. Horvath for technical support.
The authors declare no competing interests.
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Supplementary Tables 1–15 and Supplementary Figures 1–14
Data for time-of-development assays based on morphological criteria. Includes data for time-of-development assays and molting curves shown in Figs. 1b and 3b,d, and Supplementary Figs. 5b, 7b,c, 9 and 12b,c.
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Ludewig, A.H., Artyukhin, A.B., Aprison, E.Z. et al. An excreted small molecule promotes C. elegans reproductive development and aging. Nat Chem Biol 15, 838–845 (2019). https://doi.org/10.1038/s41589-019-0321-7
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