A Stochastic Step Model of Replicative Senescence Explains ROS Production Rate in Ageing Cell Populations

摘要: Increases in cellular Reactive Oxygen Species (ROS) concentration with age have been observed repeatedly mammalian tissues. Concomitant increases the proportion of replicatively senescent cells ageing tissues also observed. Populations mitotic human fibroblasts cultured vitro, undergoing transition from proliferation competence to replicative senescence are useful models Similar exponential ROS this model system. Tracking individual dividing populations is difficult, and so vast majority observations cross-sectional, at population level, rather than longitudinal cells. One possible explanation for these an increase time (e.g. resulting a vicious cycle between damage). However, we demonstrate alternative, simple hypothesis, equally consistent which does not depend on any gradual concentration: Stochastic Step Model Replicative Senescence (SSMRS). We that, SSMRS, neither proliferation-competent age, nor hTERT overexpressing passaged beyond Hayflick limit, display high concentrations. conclude that studies single their lineages now required testing hypotheses about roles mechanisms during senescence.