Telomere shortening and the population size-dependency of life span of human cell culture: further implication for two proliferation-restricting telomeres

Cultures of normal human cell can only undergo a finite number of population doublings. The proliferative life span of a culture is affected by population size, i.e., the number of cells a culture maintains. A 1000-fold transient reduction in population size can reduce the life span by as many as eight population doublings. The limited proliferative potential of human cells has been speculated to be a result of telomere shortening that occurs during DNA synthesis at each round of cell division. In this paper, I use computer simulation to test the telomere theory of cell aging against the population size-dependency of life span of human cell culture. It is found that telomere shortening well explains the above phenomenon. In addition, the results suggest that the proliferative potential of human cells might be limited by the shortening of only a few, most likely two, specific telomeres, providing further support to the same conclusion put forward in my previous paper (Tan, 1999).