MOLECULAR AND CELL BIOLOGY OF REPLICATIVE SENESCENCE
MOLECULAR AND CELL BIOLOGY OF REPLICATIVE SENESCENCE
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DOI：
10.1101/sqb.1994.059.01.010
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发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
CAMPISI, J
中科院分区：
文献类型：
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作者：
DIMRI, GP;CAMPISI, J
大约 30 年前，正式描述了细胞的有限复制寿命（Hayflick 1965）。从那时起，许多研究人员主要通过研究培养物中细胞的增殖来研究这种现象。复制性衰老的几个重要特征已经出现（综述参见 Stanulis-Praeger 1987；Goldstein 1990；McCormick 和 Campisi 1991；Peacocke 和 Campisi 1991）。首先，复制性衰老在人类细胞中尤其严格，几乎永远不会自发地永生化。这与来自几种啮齿动物物种的细胞形成鲜明对比，这些细胞以低但可检测的频率自发地永生化。尽管如此，当仔细监测细胞培养物时，很明显，来自非常多（如果不是全部）物种和器官的细胞仅分裂有限次数。其次，衰老是一种稳定状态，不是凋亡或程序性细胞死亡。衰老细胞以 G 1 DNA 含量抑制生长，但仍能长时间保持活力和代谢活性。此外，许多基因（但不是所有基因）在衰老细胞中仍然具有丝裂原诱导性，尽管事实上细胞已经失去了通过启动 DNA 复制来响应丝裂原的能力。第三，有限复制寿命表型和最终衰老状态都是体细胞融合实验中的主要表型。此外，至少已鉴定出四个可实现永生的基因互补群体。因此，复制性衰老似乎是一种遗传显性性状，并受多个遗传位点控制。第四，除了细胞增殖停止之外，复制性衰老还需要分化功能的选择性变化。因此，根据稳定且不可逆的生长停滞和细胞功能改变的标准，衰老细胞类似于终末分化细胞。然而，与终末分化相反，复制性衰老仅是完成有限数量的细胞分裂的结果。
The finite replicative life span of cells was formally described about 30 years ago (Hayflick 1965). Since then, the phenomenon has been studied by a number of investigators, primarily by studying the proliferation of cells in culture. Several important features of replicative senescence have emerged (for review, see Stanulis-Praeger 1987; Goldstein 1990; McCormick and Campisi 1991; Peacocke and Campisi 1991). First, replicative senescence is particularly stringent in human cells, which virtually never spontaneously immortalize. This is in sharp contrast to cells derived from several rodent species, which spontaneously immortalize at low but detectable frequencies. Nonetheless, when cell cultures are monitored carefully, it is clear that cells derived from very many, if not all, species and organs divide only a limited number of times.Second, senescence is a stable state and is not apoptotic or programmed cell death. Senescent cells arrest growth with a G 1 DNA content but remain viable and metabolically active for long periods of time. Moreover, many genes (but not all genes) remain mitogen-inducible in senescent cells, despite the fact that the cells have lost the ability to respond to mitogens by initiating DNA replication. Third, both the finite replicative life span phenotype and the final senescent state are dominant phenotypes in somatic cell fusion experiments. Moreover, at least four genetic complementation groups for immortality have been identified. Thus, replicative senescence appears to be a genetically dominant trait and to be controlled by multiple genetic loci. Fourth, in addition to the cessation of cell proliferation, replicative senescence entails selected changes in differentiated functions. Thus, by the criteria of a stable and irreversible growth arrest and altered cell function, senescent cells resemble terminally differentiated cells. In contrast to terminal differentiation, however, replicative senescence occurs solely as a consequence of completing a finite number of cell divisions.