engleski

Mathematical model and computer simulations of telomere loss

The molecular mechanisms that control the limited number of human cell divisions has occupied re- searchers ever since its first description in 1961. There is evidence that this limited growth capacity, re- ferred to as cellular or replicative senescence, is the basis for organismal ageing. Numerous studies point to the molecular mechanisms of telomere involvement in this phenomenon. A hallmark of cell senescence is high stochasticity where individual cells enter senescence in a completely random and stochastic fash- ion. Therefore, mathematical modelling and computational simulations of telomere dynamics are often used to explain this stochastic nature of cell ageing. Models published thus far were based on the molec- ular mechanisms of telomere biology and how they dictate the dynamics of cell culture proliferation. In the present work we propose an advanced model of telomere controlled cell senescence based on abrupt telomere shortening, thus explaining some important but thus far overlooked aspects of cell senescence. We test our theory by simulating the proliferative potential and two- sister experiment originally con- ducted by Smith and Whitney in 1980.

Replicative senescence ; Abrupt shortening ; Human fibroblasts ; Stochastic cell ageing dynamics ; Incomplete replication

nije evidentirano