Fig. 1.

Certain male reproductive cells and embryonic stem cells retain full or almost full telomere length due to expression of telomerase activity. Pluripotent stem cells have regulated telomerase activity and thus they lose telomeres throughout life but at a reduced rate. Most somatic cell do not express telomerase activity and thus lose telomere length with each division at a faster rate until the cells uncap a few of their telomeres and undergo a growth arrest called replicative senescence. In the absence of cell cycle checkpoints (e.g. p53/pRB pathway), cells bypass senescence until they reach crisis. In crisis telomeres are so short that chromosome end fusions occur and there is increased genomic instability (probably due to chromosomal, breakage, fusion, bridge cycles). A rare cell that escapes crisis almost universally does so by reactivating telomerase and this cell can now become a cancer cell with limitless potential to divide. Almost all cancer cells have short telomeres and thus inhibitors of telomerase should drive such cancer cells into apoptotic cell death.