Aging in mammalian cell population: a review

Research on in vitro aging and development is reviewed within a framework provided by three aspects of population growth--birth, canalization and death. Although there are periodic changes in the birth rate coupled to periodic changes in the in vitro environment, there do not appear to be any age-related changes in the birth rate of dividing cells. There appear to be distinct subpopulations of dividing and nondividing cells, each with its own characteristic morphological and functional properties; thus, Weiss-Kavanaugh theory may be applicable to the growth, maturation and senescence of mammalian cell populations. Substantial cell losses occur during subcultivation and transfer; correction for these losses requires substantial reinterpretation of existing experimental findings. The various measures of age are poorly correlated with one another; there is wide variation from population to population. A uniform measure of age has been found in the cell generation, the number of ancestors of a given cell. Studies of intrinsic variation in development can provide additional insight into the developmental process. The framework of birth, canalization and death permits reduction in the number of competing hypotheses of aging in mammalian cell populations. Additional experimental evidence is needed to discriminate among the remaining hypotheses.