Gene expression patterns in calorically restricted mice: Partial overlap with long-lived mutant mice

Gene expression patterns in calorically restricted mice: Partial overlap with long-lived mutant mice
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DOI:
10.1210/me.2002-0142
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发表时间:
2002-11-01
影响因子:
--
通讯作者:
Bartike, A
Bartike, A
中科院分区:
医学2区
文献类型:
--
作者:
Miller, RA;Chang, YY;Bartike, A

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为了深入了解卡路里限制(CR)延缓衰老的途径,对9个月大的CR和对照组小鼠肝脏中2352个基因的基因表达水平进行了评估。共发现352个基因在CR中显著增加或减少。受影响的基因在功能类中的分布类似于测试集中的基因分布。令人惊讶的是,生长激素受体(GHR-KO)基因的中断或敲除对基因表达的影响要小得多,符合选择标准的基因不超过10个。GHR-KO也能延长寿命。然而,GHR-KO突变与CR饮食之间存在交互作用:CR对GHR-KO小鼠基因表达的影响显著低于对照组小鼠。在CR显著改变的352个基因中,29个在先前的肝脏基因表达研究中显示出显著的和平行的表达变化,该研究将长寿的Snell矮小种群(dw/dw)的小鼠与对照组进行了比较。这29个基因都被CR和矮小鼠改变,提供了两种延迟衰老模型的共同生化特征清单,因此值得证实和更详细的研究。
To gain insight into the pathways by which caloric restriction (CR) slows aging, gene expression levels were assessed for each of 2352 genes in the livers of 9-month-old CR and control mice. A total of 352 genes were found to be significantly increased or decreased by CR. The distribution of affected genes among functional classes was similar to the distribution of genes within the test set. Surprisingly, a disruption or knockout of the gene for the GH receptor (GHR-KO), which also produces life extension, had a much smaller effect on gene expression, with no more than 10 genes meeting the selection criterion. There was, however, an interaction between the GHR-KO mutation and the CR diet: the effects of CR on gene expression were significantly lower in GHR-KO mice than in control mice. Of the 352 genes altered significantly by CR, 29 had shown a significant and parallel alteration in expression in a previous study of liver gene expression that compared mice of the long-lived Snell dwarf stock (dw/dw) to controls. These 29 genes, altered both by CR and in dwarf mice, provide a list of biochemical features common to both models of delayed aging, and thus merit confirmation and more detailed study.