Cultured human fibroblasts: distribution of cell generations and a critical limit.

In circular outgrowths of human skin fibroblasts we found that mitotic cells at the circumference had consumed more of their replicative lifespan than cells located more centrally. The lifespan remaining in cells at a given radial position could be predicted by determining their generation level based on the rate at which the outgrowth expanded and the cell doubling time. The data also show that outgrowths contain a heterogeneous mixture of cells described by a linear distribution of generations which can account for the variable replicative capacity observed in clones and the exponential increase in the fraction of nondividing cells with serial passage. These results support the concept that a critical limit of cell divisions determines the replicative lifespan.