The waste-product theory of aging: transformation to unlimited growth in cell cultures.

A differential equation governing intracellular waste content is solved numerically to determine the circumstances under which the growth of an in vitro cell population is limited. Parameter values derived from data on human glial cell cultures are employed. It is assumed that a) waste accumulation depresses the rate of cellular reproduction and b) intracellular waste is diluted by cell division, but is not otherwise eliminated. Population size depends upon two parameters: the rate of waste production and the rate of cell division in the absence of waste. If the rate of waste production is sufficient, the population size approaches an asymptote as in phase III growth in vitro. If a lower rate of waste production allows the cells to outmultiply the waste, growth is unlimited as in a transformed cell population. The asymptotic population size and the threshold for unlimited growth are remarkably sensitive to small changes in the values of the two rate parameters unless the ratio of their values is constant. This suggests that there may be a cellular mechanism that relates the waste production and cell division rates.