Cell senescence: an evaluation of replicative senescence in culture as a model for cell aging in situ.
Cell senescence: an evaluation of replicative senescence in culture as a model for cell aging in situ.
复制标题
细胞衰老：作为原位细胞衰老模型对培养物中的复制衰老进行评估。
DOI：
10.1093/gerona/58.9.b776
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Allen,RG
中科院分区：
文献类型：
--
作者：
Cristofalo,VincentJ;Beck,Jeanne;Allen,RG
来自不同组织的成纤维细胞的有限复制寿命通常被作为生物衰老的模型来研究(1，2)。毫无疑问，衰老过程中的器官衰竭有细胞基础。培养中的复制衰老符合细胞衰老的描述和定义；随着继代培养，种群中的增殖能力逐渐丧失，直到培养物不能再继代培养。在体内，某些类型的细胞的增殖率随着年龄的增长而逐渐减弱，这表明体内和体外的增殖调节是平行的变化(3)。因此，体外复制衰老的研究作为体内细胞变化的模型是很有吸引力的，因为它带来了细胞的实验优势，这些细胞表现出在研究者控制的环境中保持的某些衰老特征。尽管在过去的40年里发表了许多关于复制衰老的研究(例如，参考文献[Ref.3)，体外研究与体内衰老的相关性一直存在争议。主要感兴趣的问题是，我们在复制衰老中观察到的变化是否复制了细胞原位衰老的途径和机制。支持复制衰老与细胞原位衰老直接关系的主要来源之一是皮肤成纤维细胞(和其他细胞类型)在培养中的复制寿命可能随着供体年龄的增加而下降(4，5岁)。然而，未能一致地证明供者年龄与增殖寿命的这种反向关系一直是定义细胞培养模型与组织衰老的相关性的问题。事实上，使用不同年龄的健康供者的几项研究(6-8)并未证明供者年龄与复制寿命之间的关系。在最近的这些研究中，Smith和他的同事(6)提出了四个主要观点：(A)菌落大小分布(CSD)分析估计成纤维细胞的总复制寿命；(B)在使用CSD估计复制寿命的培养中，作者报告了复制寿命没有随着供者年龄的变化而显著下降。然而，当比较仅来自女性的培养时，他们发现估计的复制寿命有小幅但显著的下降；(C)对于男性和女性捐赠者，
THE limited replicative life span of fibroblasts derived from various human tissues is commonly studied as a model of biological aging (1, 2). There is little doubt that organismic failures in aging have a cellular basis. Replicative senescence in culture fits the description and definition of cell senescence; with subcultivation, there is a gradual loss of proliferative capacity in the population until the culture can no longer be subcultivated. In vivo, there is a gradual attenuation of proliferation rates of some cell types with age, suggesting parallel changes in proliferative regulation in vivo and in vitro (3). Thus the study of replicative senescence in vitro as a model for cellular changes in vivo is attractive since it brings the experimental advantage of cells that exhibit some features of senescence that are maintained in an environment that is under the control of the investigator. Despite numerous published studies on replicative senescence over the last 40 years (eg, Ref. 3), the relevance of in vitro studies to aging in vivo has been controversial. The question of major interest is whether the changes we observe in replicative senescence duplicate the pathways and mechanisms of cell senescence in situ. One of the major sources of support for the direct relationship of replicative senescence to cell senescence in situ has been the putative decline in the replicative life span of skin fibroblasts (and other cell types) in culture as a function of donor age (4, 5). However, failure to consistently show this inverse relationship of donor age to proliferative life span has been problematic for defining the relevance of the cell culture model to organismic aging.In fact, several studies (6–8) using healthy donors of different ages have not demonstrated a relationship between donor age and replicative life span. In the most recent of these studies that address this putative relationship, Smith and colleagues (6) make four major points:(a) colony size distribution (CSD) analysis estimates the total replicative life span of fibroblasts;(b) in cultures using CSD to estimate replicative life span, the authors report no significant decline of replicative life span as a function of donor age. However, when comparing cultures derived from females only, they detected a small but significant decline in estimated replicative life span;(c) for both male and female donors, the