Nutritional programming of lifespan by FOXO inhibition on sugar-rich diets

Dobson, A. J. , Ezcurra, M., Flanagan, C. E., Summerfield, A. C., Piper, M. D.W., Gems, D. and Alic, N. (2017) Nutritional programming of lifespan by FOXO inhibition on sugar-rich diets. Cell Reports, 18(2), pp. 299-306. (doi: 10.1016/j.celrep.2016.12.029) (PMID:28076775) (PMCID:PMC5263231)

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Abstract

Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO—the Drosophila homolog of forkhead box O (FOXO) transcription factors—and represses expression of dFOXO target genes encoding epigenetic regulators. Crucially, dfoxo is required both for transcriptional changes that mark the fly’s dietary history and for nutritional programming of lifespan by excess dietary sugar, and this mechanism is conserved in Caenorhabditis elegans. Our study implicates FOXO factors, the evolutionarily conserved determinants of animal longevity, in the mechanisms of nutritional programming of animal lifespan.

Item Type:Articles
Additional Information:The authors acknowledge funding from the Biotechnology and Biological Sciences Research Council (to N.A.; BB/M029093/1), Medical Research Council (to N.A.; MR/L018802/1), Royal Society (to N.A.: RG140694; to M.D.W.P.: UF100158 and RG110303), Wellcome Trust (to D.G.; WT098565/Z/12/Z), and Australian Research Council (to M.D.W.P.; FT150100237).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dobson, Dr Adam
Authors: Dobson, A. J., Ezcurra, M., Flanagan, C. E., Summerfield, A. C., Piper, M. D.W., Gems, D., and Alic, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN:2211-1247
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Cell Reports 18(2): 299-306
Publisher Policy:Reproduced under a Creative Commons License

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