Testing the commitment theory of cellular aging.

The commitment theory may explain both the finite lifespan of diploid fibroblasts and the apparent immortality of transformed lines. Potentially immortal cells are assumed on division to generate with some fixed probability cells committed to senesce after a specific number of divisions. During the period between commitment and senescence, cells are assumed to maintain normal growth so that the uncommitted cells are diluted by committed ones and may ultimately be lost in subculturing. A number of predictions of this model are described and experiments strongly supporting the theory are reported. We conclude that the limited growth of diploid fibroblasts is, in effect, an artifact of normal culturing procedures.