Does capacity of DNA replication change during in vitro ageing?

Abstract

We described elsewhere how a lack of change in the rate of DNA chain elongation occurred during in vitro ageing of human diploid fibtroblasts. Here we further examined the rate of actual incorporation of tritiated thymidine, the center-to-center distance of replicons and the length of each phase of the cell cycle in order to extend our previous results to the other aspects of DNA replication. The results obtained showed that the rate of net DNA synthesis, the replicon size and the duration of S phase did not change during in vitro ageing. Our findings indicated that the reason why the greater part of the cell population at high population doubling levels becomes incapable of proliferating might not be the gradual decline in the ability of DNA replication. The regulation system(s) of DNA replication may alter during the period of culturing without any change in the capacities of the DNA replication machinery and, consequently, the non-cycling cells increase.