Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging.
Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging.
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DOI：
10.1007/s10522-008-9197-8
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发表时间：
2009-10
期刊：
影响因子：
4.5
通讯作者：
Adjaye, James
中科院分区：
文献类型：
--
作者：
Brink, Thore C.;Demetrius, Lloyd;Lehrach, Hans;Adjaye, James
衰老速度的个体差异取决于生物体将资源转化为代谢能的效率，从而维持其细胞和组织的稳态。这一观察结果与代谢过程的分析研究相结合，得出以下原理：调节网络的代谢稳定性，即细胞维持活性氧（ROS）和其他关键代谢物稳定浓度的能力，是寿命的主要决定因素。调控网络的代谢稳定性取决于代谢途径的多样性或网络中基因的连通程度。这些特性可以根据基因表达中的转录变化进行经验评估。我们利用基因芯片研究了小鼠胰岛素信号、氧化磷酸化和谷胱甘肽代谢途径中基因转录变化的年龄依赖性。我们的研究描绘了转录变化的年龄和组织特异性模式，这与代谢稳定性长寿原则是一致的。这项研究，此外，拒绝自由基假设，假定生产率的ROS，而不是其稳定性，决定寿命。本文的在线版本（doi：10.1007/s10522-008-9197-8）包含补充材料，可供授权用户使用。
Individual differences in the rate of aging are determined by the efficiency with which an organism transforms resources into metabolic energy thus maintaining the homeostatic condition of its cells and tissues. This observation has been integrated with analytical studies of the metabolic process to derive the following principle: The metabolic stability of regulatory networks, that is the ability of cells to maintain stable concentrations of reactive oxygen species (ROS) and other critical metabolites is the prime determinant of life span. The metabolic stability of a regulatory network is determined by the diversity of the metabolic pathways or the degree of connectivity of genes in the network. These properties can be empirically evaluated in terms of transcriptional changes in gene expression. We use microarrays to investigate the age-dependence of transcriptional changes of genes in the insulin signaling, oxidative phosphorylation and glutathione metabolism pathways in mice. Our studies delineate age and tissue specific patterns of transcriptional changes which are consistent with the metabolic stability–longevity principle. This study, in addition, rejects the free radical hypothesis which postulates that the production rate of ROS, and not its stability, determines life span. The online version of this article (doi:10.1007/s10522-008-9197-8) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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