Figure 1

Schematic diagram picturing the inter-relations between DNA damage, cellular aging and cancer. As a result of DNA damage (D), induced by genotoxic stresses, mutations accumulate in individual cells (M). Cells exposed to larger amounts of stress have higher probability to accumulate more mutations. The replication of these potential mutators (i.e. tumor originating cells), is limited by the two distinct aging mechanisms: a) replicative senescence mediated by telomere attrition and b) p53 mediated cell cycle arrest and apoptosis. While the effect of p53 is rapid (can happen within several hours after the insult), the effect of telomeres is slow.