Holliday R
Fed Proc. 1975 Jan;34(1):51-5.
Three possible explanations are presented for the differences in growth potential between human diploid fibroblasts of finite life-span and permanent transformed lines: 1) Only diploid cells have a molecular clock mechanism which counts cell divisions prior to senescence. Two hypothetical examples of such mechanisms are described; however, the available evidence argues against a clock mechanism for aging in fibroblasts. 2) Cells become committed with a given probability to a slow buildup in protein errors, which leads after many divisions to a lethal error catastrophe. It can be shown that speeding up the rate at which the error catastrophe develops, as may occur in transformed cells, can convert a population of finite life-span to one with infinite growth. 3) The growth rate of diploid cells may not depend on the limiting concentration of any one protein. If so, cells with a low level of errors will not have a reduced generation time, and there will be no selection against them. On the other hand the uncontrolled growth of transformed cells may be reduced in rate by the presence of faulty proteins, so that there is continuous selection for those with the fewest errors. Finally, the analogous problem of the mortality of somatic cells and the immortality of the germ line is also briefly discussed.
对于有限寿命的人类二倍体成纤维细胞和永久转化细胞系之间生长潜力的差异，提出了三种可能的解释：1）只有二倍体细胞具有分子时钟机制，该机制在衰老前对细胞分裂进行计数。描述了这种机制的两个假设例子；然而，现有证据反驳了成纤维细胞衰老的时钟机制。2）细胞以一定概率开始逐渐积累蛋白质错误，经过多次分裂后导致致命的错误灾难。可以证明，加快错误灾难发生的速度，如在转化细胞中可能发生的那样，可以将有限寿命的群体转变为具有无限生长能力的群体。3）二倍体细胞的生长速率可能不依赖于任何一种蛋白质的极限浓度。如果是这样，错误水平低的细胞不会有缩短的世代时间，并且不会对它们进行选择。另一方面，转化细胞的失控生长可能会因存在错误蛋白质而降低速度，因此会持续选择错误最少的细胞。最后，还简要讨论了体细胞死亡率和生殖系永生的类似问题。
