Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart
Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart
复制标题
DOI：
10.1016/j.exger.2008.06.013
复制
发表时间：
2008-09-01
影响因子：
3.9
通讯作者：
Weindruch, R.
中科院分区：
文献类型：
--
作者：
Barger, J. L.;Kayo, T.;Weindruch, R.
衰老研究的一个活跃领域集中在识别具有模拟热量限制(CR)效果的化合物。从2到5个月龄，我们给雄性B6C3F(1)小鼠饲喂40%CR饲料、添加含有白藜芦醇、栎素和六磷酸肌醇的商品营养混合物(NCM)的对照饲料，或者从2到5个月龄添加等量化学级白藜芦醇(RES；1.25 mg白藜芦醇kg(-1)day(-1))的饲料。三组处理小鼠的心脏基因表达谱被生成，并与年龄匹配的对照(CO)小鼠进行比较。所有三种治疗都与几个细胞骨架维持途径的变化有关，这表明Res和NCM能够模拟短期CR。CR只影响几条免疫功能通路，而RES只影响多条应激反应通路。通路分析表明，NCM(而不是CR或Res)调节多种代谢途径，这些途径也被长期的CR改变，包括葡萄糖和脂肪代谢、氧化磷酸化和染色质组装。对受NCM影响的关键基因和途径的研究表明，Foxo1是其作用的关键上游调节因子。(C)2008 Elsevier Inc.保留所有权利。
An active area of aging research is focused on identifying Compounds having the ability to mimic the effects of caloric restriction (CR). From 2 to 5 months of age, we fed male B6C3F(1) mice either a 40% CR diet, a control diet supplemented with a commercially available nutraceutical mixture (NCM) containing resveratrol, quercetin and inositol hexaphosphate, or a diet supplemented with an equivalent dose of chemical-grade resveratrol (RES; 1.25 mg resveratrol kg(-1) day(-1)) from 2 to 5 months of age. Cardiac gene expression profiles were generated for the three groups of treated mice and compared to age-matched control (CO) mice. All three treatments were associated with changes in several cytoskeletal maintenance pathways, suggesting that RES and NCM are able to mimic short-term CR. CR uniquely affected several immune function pathways while RES uniquely affected multiple stress response pathways. Pathway analysis revealed that NCM (but not CR or RES) regulated multiple metabolic pathways that were also changed by long-term CR, including glucose and lipid metabolism, oxidative phosphorylation and chromatin assembly. Examination of key genes and pathways affected by NCM suggests that Foxo1 is a critical upstream mediator of its actions. (C) 2008 Elsevier Inc. All rights reserved.