Stress induced telomere shortening: longer life with less mutations?

ABSTRACT: BACKGROUND: Mutations accumulate as a result of DNA damage and imperfect DNA repair machinery. In higher eukaryotes the accumulation and spread of mutations is limited in two primary ways: through p53-mediated programmed cell death and cellular senescence mediated by telomeres. Telomeres shorten at every cell division and cell stops dividing once the shortest telomere reaches a critical length. It has been shown that the rate of telomere attrition is accelerated when cells are exposed to DNA damaging agents. However the implications of this mechanism are not fully understood. RESULTS: With the help of in silico model we investigate the effect of genotoxic stress on telomere attrition and apoptosis in a population of non-identical replicating cells. When comparing the populations of cells with constant vs. stress-induced rate of telomere shortening we find that stress induced telomere shortening (SITS) increases longevity while reducing mutation rate. Interestingly, however, the effect takes place only when genotoxic stresses (e.g. reactive oxygen species due to metabolic activity) are distributed non-equally among cells. CONCLUSIONS: Our results for the first time show how non-equal distribution of metabolic load (and associated genotoxic stresses) combined with stress induced telomere shortening can delay aging and minimize mutations.

SUBMITTER: Trusina A 

PROVIDER: S-EPMC4015310 | biostudies-other | 2014

REPOSITORIES: biostudies-other