Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets

被引：45

作者：

Dobson, Adam J. ^{[1
,2
]}

Ezcurra, Marina ^{[1
,2
]}

Flanagan, Charlotte E. ^{[1
,2
,4
]}

Summerfield, Adam C. ^{[1
,2
,5
]}

Piper, Matthew D. W. ^{[3
]}

Gems, David ^{[1
,2
]}

Alic, Nazif ^{[1
,2
]}

机构：

[1] UCL, Inst Hlth Ageing, Gower St, London WC1E 6BT, England

[2] UCL, Dept Genet Evolut & Environm, Gower St, London WC1E 6BT, England

[3] Monash Univ, Sch Biol Sci, Melbourne, Vic 3800, Australia

[4] Kings Coll London, Guys Hosp, Fac Life Sci & Med, 2nd Floor Borough Wing,Great Maze Pond, London SE1 9RT, England

[5] Friedrich Schiller Univ Jena, Dept Biochem, Ctr Mol Biomed, Inst Biochem & Biophys, Hans Knoll Str 2, D-07745 Jena, Germany

来源：

CELL REPORTS | 2017年 / 18卷 / 02期

基金：

英国生物技术与生命科学研究理事会; 澳大利亚研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; HUMAN LONGEVITY; FAT-BODY; RESTRICTION; STRESS; DFOXO; DISEASE; OBESITY; MORTALITY;

D O I：

10.1016/j.celrep.2016.12.029

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：299 / 306

页数：8

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