The biology of replicative senescence
The biology of replicative senescence
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DOI：
10.1016/s0959-8049(96)00058-5
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发表时间：
1997-04-01
影响因子：
8.4
通讯作者：
Campisi, J
中科院分区：
文献类型：
--
作者：
Campisi, J
大多数细胞不能无限期地分裂，这是由于称为细胞或复制衰老的过程。复制性衰老似乎是体细胞的基本特征，除了大多数肿瘤细胞和可能的某些干细胞。细胞如何感知它们完成的分裂次数？虽然还没有经过严格的检验，端粒缩短假说可能是目前对细胞分裂“计数”机制的最佳解释。为什么细胞在完成有限次数的分裂后不可逆地停止增殖？现在已经知道，复制性衰老改变了一些重要的生长调节基因的表达。在高等真核生物中，这些生长调节基因表达的变化与端粒缩短的关系尚不清楚。然而，低等真核生物已经提供了几种可能的机制。最后，复制性衰老的生理后果是什么？几条证据表明，至少在人类细胞中，复制衰老是一种强大的肿瘤抑制机制。也有间接证据表明，复制性衰老有助于衰老。总之，目前的研究结果表明，至少在哺乳动物中，复制性衰老可能已经进化到减少肿瘤发生，但也可能具有促进年龄相关病理学的副作用，包括癌症。(C)1997年爱思唯尔科学有限公司
Most cells cannot divide indefinitely due to a process termed cellular or replicative senescence. Replicative senescence appears to be a fundamental feature of somatic cells, with the exception of most tumour cells and possibly certain stem cells. How do cells sense the number of divisions they have completed? Although it has not yet been critically tested, the telomere shortening hypothesis is currently perhaps the best explanation for a cell division 'counting' mechanism. Why do cells irreversibly cease proliferation after completing a finite number of divisions? It is now known that replicative senescence alters the expression of a few crucial growth-regulatory genes. It is not known how these changes in growth-regulatory gene expression are related to telomere shortening in higher eukaryotes. However, lower eukaryotes have provided several plausible mechanisms. Finally, what are the physiological consequences of replicative senescence? Several lines of evidence suggest that, at least in human cells, replicative senescence is a powerful tumour suppressive mechanism. There is also indirect evidence that replicative senescence contributes to ageing. Taken together current findings suggest that, at least in mammals, replicative senescence may have evolved to curtail tumorigenesis, but may also have the unselected effect of contributing to age-related pathologies, including cancer. (C) 1997 Elsevier Science Ltd.