Note on the dispersion of generations among cells in senescing diploid fibroblast populations.

The cells in a cultured diploid fibroblast population have heterogeneous intermitotic times--even cells derived from the same mitosis may divide at different ages. This heterogeneity of inter-mitotic times results in asynchronous population growth and a dispersion of generations among members of the cell population. Because the appearance of non-dividing cells in middle-age populations has been attributed to the presence of lineages with more generations than average, we estimated the magnitude of the dispersion of cell generations as functions of the population doubling level and of the coefficient of variation of inter-mitotic times. For some data, such as that of Macieira-Coelho and Azzarone (Exp. Cell Res., 141 (1982) 325, the rate at which such non-proliferating lineages appear could be explained by a reasonable coefficient of variation of inter-mitotic times (25%). Most other data, however, would be fit only if the coefficient of variation of inter-mitotic times were 50% or greater, a variability that exceeds what has been observed in microcinematography experiments.