An excreted small molecule promotes C. elegans reproductive development and aging

Andreas H. Ludewig; Alexander B. Artyukhin; Erin Z. Aprison; Pedro R. Rodrigues; Dania C. Pulido; Russell N. Burkhardt; Oishika Panda; Ying K. Zhang; Pooja Gudibanda; Ilya Ruvinsky; Frank C. Schroeder

doi:10.1038/s41589-019-0321-7

An excreted small molecule promotes C. elegans reproductive development and aging

Andreas H. Ludewig, Alexander B. Artyukhin, Erin Z. Aprison, Pedro R. Rodrigues, Dania C. Pulido, Russell N. Burkhardt, Oishika Panda, Ying K. Zhang, Pooja Gudibanda, Ilya Ruvinsky, Frank C. Schroeder^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

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.

Original language	English (US)
Pages (from-to)	838-845
Number of pages	8
Journal	Nature Chemical Biology
Volume	15
Issue number	8
DOIs	https://doi.org/10.1038/s41589-019-0321-7
State	Published - Aug 1 2019

Funding

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.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1038/s41589-019-0321-7

Cite this

@article{c21c22215a624e35a9ba01fbc34b6f3e,

title = "An excreted small molecule promotes C. elegans reproductive development and aging",

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.",

author = "Ludewig, {Andreas H.} and Artyukhin, {Alexander B.} and Aprison, {Erin Z.} and Rodrigues, {Pedro R.} and Pulido, {Dania C.} and Burkhardt, {Russell N.} and Oishika Panda and Zhang, {Ying K.} and Pooja Gudibanda and Ilya Ruvinsky and Schroeder, {Frank C.}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = aug,

day = "1",

doi = "10.1038/s41589-019-0321-7",

language = "English (US)",

volume = "15",

pages = "838--845",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - An excreted small molecule promotes C. elegans reproductive development and aging

AU - Ludewig, Andreas H.

AU - Artyukhin, Alexander B.

AU - Aprison, Erin Z.

AU - Rodrigues, Pedro R.

AU - Pulido, Dania C.

AU - Burkhardt, Russell N.

AU - Panda, Oishika

AU - Zhang, Ying K.

AU - Gudibanda, Pooja

AU - Ruvinsky, Ilya

AU - Schroeder, Frank C.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85069515610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069515610&partnerID=8YFLogxK

U2 - 10.1038/s41589-019-0321-7

DO - 10.1038/s41589-019-0321-7

M3 - Article

C2 - 31320757

AN - SCOPUS:85069515610

SN - 1552-4450

VL - 15

SP - 838

EP - 845

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 8

ER -

An excreted small molecule promotes C. elegans reproductive development and aging

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this