The effects of age and dietary restriction on the tissue-specific metabolome of Drosophila.
The effects of age and dietary restriction on the tissue-specific metabolome of Drosophila.
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DOI：
10.1111/acel.12358
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发表时间：
2015-10
期刊：
影响因子：
7.8
通讯作者：
Promislow DE
中科院分区：
文献类型：
--
作者：
Laye MJ;Tran V;Jones DP;Kapahi P;Promislow DE
饮食限制(DR)是一种强有力的干预措施，可以延长寿命，减缓不同生物体中与年龄相关的疾病的发生。虽然在试图揭示DR的遗传机制方面取得了重大进展，但关于DR对代谢物的影响的研究很少。近年来，代谢组谱已经成为了解自然衰老和疾病相关表型的分子原因和后果的一项强大的技术。在这里，我们使用高分辨率质谱学和新的计算方法来检测不同年龄的果蝇头部、胸部、腹部和全身代谢物的变化，这些果蝇喂食了营养丰富的随意(AL)或营养受限(DR)的食物。多变量分析明确了不同组织、不同年龄不同饮食的代谢物。DR显著改变了代谢物，特别是减缓了代谢物中与年龄相关的变化。有趣的是，我们观察到相互作用的代谢物，其相关系数，但不是平均水平，在AL和DR之间存在显著差异。在DR饮食下，正相关代谢物的数量和大小更大。此外，在食用AL饮食的果蝇中，正代谢物相关性降低。相反，DR增强了这些与年龄的相关性。代谢集浓缩分析确定了几个已知的(例如，氨基酸和NAD代谢)和新的代谢途径，它们可能影响DR如何影响衰老。我们的结果提示，代谢物的网络结构在DR时发生改变，可能在防止随年龄增长的动态平衡下降中发挥重要作用。
Dietary restriction (DR) is a robust intervention that extends lifespan and slows the onset of age-related diseases in diverse organisms. While significant progress has been made in attempts to uncover the genetic mechanisms of DR, there are few studies on the effects of DR on the metabolome. In recent years, metabolomic profiling has emerged as a powerful technology to understand the molecular causes and consequences of natural aging and disease-associated phenotypes. Here, we use high-resolution mass spectroscopy and novel computational approaches to examine changes in the metabolome from the head, thorax, abdomen, and whole body at multiple ages in Drosophila fed either a nutrient-rich ad libitum (AL) or nutrient-restricted (DR) diet. Multivariate analysis clearly separates the metabolome by diet in different tissues and different ages. DR significantly altered the metabolome and, in particular, slowed age-related changes in the metabolome. Interestingly, we observed interacting metabolites whose correlation coefficients, but not mean levels, differed significantly between AL and DR. The number and magnitude of positively correlated metabolites was greater under a DR diet. Furthermore, there was a decrease in positive metabolite correlations as flies aged on an AL diet. Conversely, DR enhanced these correlations with age. Metabolic set enrichment analysis identified several known (e.g., amino acid and NAD metabolism) and novel metabolic pathways that may affect how DR effects aging. Our results suggest that network structure of metabolites is altered upon DR and may play an important role in preventing the decline of homeostasis with age.