Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets.
Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets.
复制标题
Foxo抑制糖饮食的寿命的营养编程。
DOI：
10.1016/j.celrep.2016.12.029
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发表时间：
2017-01-10
期刊：
影响因子：
8.8
通讯作者：
Alic N
中科院分区：
文献类型：
--
作者：
Dobson AJ;Ezcurra M;Flanagan CE;Summerfield AC;Piper MDW;Gems D;Alic N
不健康饮食的消费加剧了老龄人口中与年龄有关的健康状况不佳的负担。这样的饮食可以编程哺乳动物的生理造成长期的，有害的影响。在这里，我们表明，在黑腹果蝇，不健康的，高糖饮食在成年早期程序的寿命缩短以后的生活生存，尽管随后的饮食改善。过量的膳食糖促进胰岛素样信号传导，抑制dFOXO-果蝇的叉头盒O（FOXO）转录因子的同源物-并抑制dFOXO靶基因编码表观遗传调节因子的表达。至关重要的是，dfoxo是必需的转录变化，标志着苍蝇的饮食历史和营养规划的寿命过量的饮食糖，这种机制是保守的秀丽隐杆线虫。我们的研究暗示FOXO因子，动物寿命的进化保守的决定因素，在动物寿命的营养规划的机制。高糖使dFOXO失活，改变染色质修饰物的mRNA水平dfoxo是响应高糖的长期转录变化所必需的dfoxo和daf-16是高糖饮食对寿命编程所必需的现代饮食可能对长期健康产生负面影响。多布森等表明高糖饮食通过调节叉头盒O转录因子来规划苍蝇和蠕虫寿命。
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. A high-sugar diet in early life programs Drosophila lifespan High sugar inactivates dFOXO, altering mRNA levels of chromatin modifiers dfoxo is required for long-term transcriptional changes in response to high sugar dfoxo and daf-16 are required for programming of lifespan by high-sugar diets Modern diets can have negative consequences for long-term health. Dobson et al. show that high-sugar diets program fly and worm lifespan through the regulation of forkhead box O transcription factors.