Aging in Mouse and Human Systems A Comparative Study
Aging in Mouse and Human Systems A Comparative Study
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DOI：
10.1196/annals.1354.010
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Demetrius, Lloyd
中科院分区：
文献类型：
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作者：
Demetrius, Lloyd
本文讨论了小鼠模型作为阐明人类衰老过程基础的重要性。我们确定了小鼠和人类系统之间的某些相似之处，并回顾了理论和经验支持，即两个物种之间衰老速度的巨大差异在于其代谢网络稳定性的差异。我们将证明，代谢稳定性的这些差异源于物种在进化历史中经历的不同生态限制。我们利用这些想法来比较热量限制对小鼠和人类系统的影响。研究预测，在受热量限制的实验室啮齿类动物中观察到的平均寿命和最大寿命潜力的大幅增加，在人类群体中不会实现。我们预测，鉴于两个系统的代谢稳定性不同，热量限制不会对人类的最大寿命潜力产生影响，对非肥胖人群的平均寿命影响相对较小。因此，本文指出了使用小鼠模型来阐明人类衰老过程的某些内在局限性。我们还认为，通过考虑两个物种的代谢稳定性可以减轻这些限制。
This article discusses the significance of mouse models as a basis for elucidating the aging process in humans. We identify certain parallels between mouse and human systems and review the theoretical and empirical support for the claim that the large divergence in the rate of aging between the two species resides in differences in the stability of their metabolic networks. We will show that these differences in metabolic stability have their origin in the different ecological constraints the species experience during their evolutionary history. We exploit these ideas to compare the effect of caloric restriction on murine and human systems. The studies predict that the large increases in mean life span and maximum life-span potential observed in laboratory rodents subject to caloric restriction will not obtain in human populations. We predict that, in view of the different metabolic stability of the two systems, caloric restriction will have no effect on the maximum life-span potential of humans, and a relatively minor effect on the mean life span of nonobese populations. This article thus points to certain intrinsic limitations in the use of mouse models in elucidating the aging process in humans. We furthermore contend the view that these limitations can be mitigated by considering the metabolic stability of the two species.