Explaining differences in the lifespan and replicative capacity of cells: a general model and comparative analysis of vertebrates.

A better understanding of the factors that govern individual cell lifespan and the replicative capacity of cells (i.e. Hayflick's limit) is important for addressing disease progression and ageing. Estimates of cell lifespan in vivo and the replicative capacity of cell lines in culture vary substantially both within and across species, but the underlying reasons for this variability remain unclear. Here, we address this issue by presenting a quantitative model of cell lifespan and cell replicative capacity. The model is based on the relationship between cell mortality and metabolic rate, which is supported with data for different cell types from ectotherms and endotherms. These data indicate that much of the observed variation in cell lifespan and cell replicative capacity is explained by differences in cellular metabolic rate, and thus by the three primary factors that control metabolic rate: organism size, organism temperature and cell size. Individual cell lifespan increases as a power law with both body mass and cell mass, and decreases exponentially with increasing temperature. The replicative capacity of cells also increases with body mass, but is independent of temperature. These results provide a point of departure for future comparative studies of cell lifespan and replicative capacity in the laboratory and in the field.