  Mammalian cells are restricted from proliferating indefinitely. Telomeres at
the end of each chromosome are shortened at cell division and, when they reach
a critical length, the cell will enter permanent cell cycle arrest - a state
known as senescence. This mechanism is thought to be tumor suppressing, as it
helps prevent precancerous cells from dividing uncontrollably.
  Stem cells express the enzyme telomerase, which elongates the telomeres,
thereby postponing senescence. However, unlike germ cells and most types of
cancer cells, stem cells only express telomerase at levels insufficient to
fully maintain the length of their telomeres leading to a slow decline in
proliferation potential. It is not yet fully understood how this decline
influences the risk of cancer and the longevity of the organism. We here
develop a stochastic model to explore the role of telomere dynamics in relation
to both senescence and cancer. The model describes the accumulation of
cancerous mutations in a multicellular organism and creates a coherent
theoretical framework for interpreting the results of several recent
experiments on telomerase regulation. We demonstrate that the longest average
cancer free life span before cancer onset is obtained when stem cells start
with relatively long telomeres that are shortened at a steady rate at cell
division. Furthermore, the risk of cancer early in life can be reduced by
having a short initial telomere length. Finally, our model suggests that
evolution will favour a shorter than optimal average cancer free life span in
order to postpone cancer onset until late in life.
