Telomeres and telomerase: the commitment theory of cellular ageing revisited

It is not always realised that separate fibroblast populations of the same strain have very different lifespans, that is, over a million-fold range. This is best documented for human strains WI-38 and MRC-5. There is evidence that it is the molecular clock of telomere shortening which determines the growth potential of these cells. However, if a clock is set and runs its course one would expect parallel cultures to have similar lifespans. The commitment theory of fibroblast ageing proposes that commitment occurs during early cell divisions with a given probability and after that there is then a constant number of divisions until growth ceases. This constant number could be determined by the gradual loss of telomeres. The stochastic feature of the theory is the probability of the loss of the last uncommitted cells or the youngest committed cells. These cells have the longest lifespan and will give rise to the final population.