Cell cycle and the concept of physiological age with special reference to pyruvate kinase activity in WI-38 cells

WI-38 cells were synchronized by mitotic collection and periodically assayed for pyruvate kinase activity. The kinetics of the synchronous cohort were determined by continuous labelling index and by mitotic index. The experimental data were analysed by computer using a state vector model to yield the probability density functions for phase transit times and for cell physiological ages. Pyruvate kinase activity for these cells as a function of physiological age was then examined using the computer model. Considering DNA synthesis, pyruvate kinase activity and mitosis to be markers of physiological age, it was found that a model which assumes that a cohort of synchronized cells desynchronizes irreversibly and uniformly from one age marker to the next is incompatible with the experimental data. For example, the times over which cells entered the S phase were too widely distributed to be consistent with the mitotic index data. Also, for pyruvate kinase activity to be a function of physiological age alone, the cell ages were probably too dispersed to be compatible with the experimental enzyme data. Alternative models for cell physiological ageing are presented, which are compatible with the experimental data.