The tumor suppressor p53 - Cancer and aging
The tumor suppressor p53 - Cancer and aging
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DOI：
10.4161/cc.7.7.5657
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发表时间：
2008-04-01
期刊：
影响因子：
4.3
通讯作者：
Levine, Arnold J.
中科院分区：
文献类型：
--
作者：
Feng, Zhaohui;Hu, Wenwei;Levine, Arnold J.
衰老，像许多其他的生物过程一样，受到基因的调控，这些基因位于进化过程中保存下来的通路中。胰岛素/IGF-1通路、mTOR通路和p53通路是影响长寿和癌症等衰老相关疾病的保守通路。大多数癌症发生在生命的最后四分之一，频率随时间呈指数增长，个体细胞中关键基因（如p53）在一生中的突变积累被认为是原因。最近，我们发现p53对应激反应的效率随着小鼠年龄的增长而显著下降，并且这种下降的p53反应开始的时间与小鼠的寿命有关。考虑到p53在肿瘤预防中的关键作用，在老年动物中p53活性的下降可能有助于观察到的癌症频率的急剧增加，并为肿瘤发生和衰老之间的相关性提供了一个合理的解释，以及DNA突变在一生中的积累。我们在此讨论p53通路和IGF-1-mTOR通路之间的协调和沟通，以及它们对癌症和寿命的可能影响。
Aging, like many other biological processes, is subject to regulation by genes that reside in pathways that have been conserved during evolution. The insulin/IGF-1 pathway, mTOR pathway and p53 pathway are among those conserved pathways that impact upon longevity and aging-related diseases such as cancer. Most cancers arise in the last quarter of life span with the frequency increasing exponentially with time, and mutation accumulation in critical genes (e. g., p53) in individual cells over a lifetime is thought to be the reason. Recently, we found that the efficiency of the p53 response to stress declines significantly with age in mice, and the time of onset of this decreased p53 response correlates with the life span of mice. Given the crucial role of the p53 in tumor prevention, this decline in p53 activity at older ages in animals could contribute to the observed dramatic increases in cancer frequency, and provides a plausible explanation for the correlation between tumorigenesis and aging in addition to the accumulation of DNA mutations over lifetime. We discuss here the coordination and communication between the p53 pathway and the IGF-1-mTOR pathways, and their possible impact on cancer and longevity.