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Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor

Alic, N; Hoddinott, MP; Vinti, G; Partridge, L; (2011) Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor. Aging Cell , 10 (1) 137 - 147. 10.1111/j.1474-9726.2010.00653.x. Green open access

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Abstract

P>Mammals possess multiple insulin-like growth factor (IGF) binding proteins (IGFBPs), and related proteins, that modulate the activity of insulin/IGF signalling (IIS), a conserved neuroendocrine signalling pathway that affects animal lifespan. Here, we examine if increased levels of an IGFBP-like protein can extend lifespan, using Drosophila as the model organism. We demonstrate that Imaginal morphogenesis protein-Late 2 (IMP-L2), a secreted protein and the fly homologue of the human IGFBP7 tumour suppressor, is capable of binding at least two of the seven Drosophila insulin-like peptides (DILPs), namely native DILP2 and DILP5 as present in the adult fly. Increased expression of Imp-L2 results in phenotypic changes in the adult consistent with down-regulation of IIS, including accumulation of eIF-4E binding protein mRNA, increase in storage lipids, reduced fecundity and enhanced oxidative stress resistance. Increased Imp-L2 results in up-regulation of dilp2, dilp3 and dilp5 mRNA, revealing a feedback circuit that is mediated via the fly gut and/or fat body. Importantly, over-expression of Imp-L2, ubiquitous or restricted to DILP-producing cells or gut and fat body, extends lifespan. This enhanced longevity can also be observed upon adult-onset induction of Imp-L2, indicating it is not attributable to developmental changes. Our findings point to the possibility that an IGFBP or a related protein, such as IGFBP7, plays a role in mammalian aging.

Type: Article
Title: Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/j.1474-9726.2010.00653.x
Publisher version: http://dx.doi.org/10.1111/j.1474-9726.2010.00653.x
Language: English
Additional information: © 2011 The Authors. Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://olabout.wiley.com/WileyCDA/Section/id-406241.html.
Keywords: aging, Drosophila, IMP-L2, insulin, insulin-like growth factor signalling, insulin-like growth factor-binding protein, insulin-like peptides, human longevity, fat-body, cells, receptor, protein, growth, brain, dFOXO, association
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/375166
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