Collins J M, Chu A K
J Cell Physiol. 1985 Jul;124(1):165-73. doi: 10.1002/jcp.1041240126.
It is well known that cell proliferation (and hence, DNA synthesis) declines in human diploid fibroblast-like cells with increasing passage number. It is not clear whether DNA synthesis declines in the remaining cells that are still actively proliferating. Estimations of cell kinetic parameters permitted extrapolations to be made that reflected the declining numbers of cells still capable of DNA replication. DNA synthesis declined with culture age in intact cells, permeabilized cells, and in the isolated nuclear matrix even when corrected for declining numbers of proliferating cells. With age, DNA polymerase alpha and beta activity in cell lysates declined, but when corrected for the remaining proliferating cells, only polymerase alpha activity declined; DNA polymerase alpha and beta activity bound to the nuclear matrix declined, but when corrected for declining proliferation, no decline was apparent for either enzyme. There was an increase in the number of S1-nuclease sensitive sites and breaks in the parental DNA of the dividing cells in older cultures. It is suggested that in aging cultures, not only does overall DNA synthesis decline owing to decreasing cell proliferation, but also that DNA synthesis declines in the remaining proliferating cells, that this decline is not due to decreasing amounts of DNA polymerase bound to the nuclear matrix, and that alterations in DNA structure occur.
众所周知，随着传代次数的增加，人二倍体成纤维样细胞中的细胞增殖（进而DNA合成）会下降。尚不清楚在仍在活跃增殖的其余细胞中DNA合成是否会下降。对细胞动力学参数的估计使得能够做出反映仍能进行DNA复制的细胞数量下降的推断。即使对增殖细胞数量的下降进行校正后，完整细胞、通透细胞以及分离的核基质中的DNA合成也会随着培养时间的延长而下降。随着年龄增长，细胞裂解物中的DNA聚合酶α和β活性下降，但校正剩余的增殖细胞后，只有聚合酶α活性下降；与核基质结合的DNA聚合酶α和β活性下降，但校正增殖下降后，这两种酶均未明显下降。在较老培养物中，分裂细胞的亲本DNA中S1核酸酶敏感位点的数量增加且出现断裂。有人提出，在老化培养物中，不仅由于细胞增殖减少导致总体DNA合成下降，而且在其余增殖细胞中DNA合成也下降，这种下降不是由于与核基质结合的DNA聚合酶数量减少，并且发生了DNA结构的改变。
