Dobson Adam J, Ezcurra Marina, Flanagan Charlotte E, Summerfield Adam C, Piper Matthew D W, Gems David, Alic Nazif
Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Gower Street, WC1E 6BT London, UK.
School of Biological Sciences, Monash University, Melbourne, VIC 3800, Australia.
Cell Rep. 2017 Jan 10;18(2):299-306. doi: 10.1016/j.celrep.2016.12.029.
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.
不健康饮食的摄入正在加剧老龄化人口中与年龄相关的健康问题负担。这类饮食会对哺乳动物的生理机能进行编程，从而产生长期的有害影响。在此，我们表明，在果蝇中，成年早期的不健康高糖饮食会对寿命进行编程，从而缩短后期的生存期，即便随后饮食有所改善。过量的膳食糖会促进胰岛素样信号传导，抑制dFOXO（果蝇中叉头框O（FOXO）转录因子的同源物），并抑制编码表观遗传调节因子的dFOXO靶基因的表达。至关重要的是，dFOXO对于标记果蝇饮食历史的转录变化以及过量膳食糖对寿命的营养编程都是必需的，并且这种机制在秀丽隐杆线虫中是保守的。我们的研究表明，FOXO因子作为动物长寿的进化保守决定因素，参与了动物寿命营养编程的机制。
