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Reduced insulin/insulin-like growth factor signaling decreases translation in Drosophila and mice

Essers, P; Tain, LS; Nespital, T; Goncalves, J; Froehlich, J; Partridge, L; (2016) Reduced insulin/insulin-like growth factor signaling decreases translation in Drosophila and mice. Scientific Reports , 6 , Article 30290. 10.1038/srep30290. Green open access

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Abstract

Down-regulation of insulin/insulin-like growth factor signaling (IIS) can increase lifespan in C. elegans, Drosophila and mice. In C. elegans, reduced IIS results in down-regulation of translation, which itself can extend lifespan. However, the effect of reduced IIS on translation has yet to be determined in other multicellular organisms. Using two long-lived IIS models, namely Drosophila lacking three insulin-like peptides (dilp2-3,5(-/-)) and mice lacking insulin receptor substrate 1 (Irs1(-/-)), and two independent translation assays, polysome profiling and radiolabeled amino acid incorporation, we show that reduced IIS lowers translation in these organisms. In Drosophila, reduced IIS decreased polysome levels in fat body and gut, but reduced the rate of protein synthesis only in the fat body. Reduced IIS in mice decreased protein synthesis rate only in skeletal muscle, without reducing polysomes in any tissue. This lowered translation in muscle was independent of Irs1 loss in the muscle itself, but a secondary effect of Irs1 loss in the liver. In conclusion, down-regulation of translation is an evolutionarily conserved response to reduced IIS, but the tissues in which it occurs can vary between organisms. Furthermore, the mechanisms underlying lowered translation may differ in mice, possibly associated with the complexity of the regulatory processes.

Type: Article
Title: Reduced insulin/insulin-like growth factor signaling decreases translation in Drosophila and mice
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/srep30290
Publisher version: http://dx.doi.org/10.1038/srep30290
Language: English
Additional information: Copyright © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/). The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/1503716
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