Diagram of TL variation according to cell division in somatic cells from physiologic to tumor state. Due to the end-replication problem in most somatic cells, loss of telomeric sequences occurs during each cell division, resulting in the gradual and predictable erosion of telomeres. When TL becomes critically short, it is believed that the telomere’s protective function is compromised. Dysfunctional telomeres are recognized as damaged DNA, which triggers a permanent growth arrest known as replicative senescence. Occasionally, cells acquire mutations (in checkpoint genes such as p53 and p16) that bypass senescence and continue to proliferate, driving further telomere erosion and culminating in a period of massive cell death and genomic instability that is termed crisis. Rare cells can escape from crisis and acquire the ability to maintain their TL, mostly by reactivating telomerase. Short telomeres associated with complex numerous chromosome aberrations and a TA seem to support that SS cells are passed-over crisis cells that have an aptitude for proliferating without limit.