a stochastic step model of replicative senescence explains ros production rate in ageing cell populations复制衰老的随机步模型解释了衰老细胞内活性氧产量数量.pdfVIP

A Stochastic Step Model of Replicative Senescence Explains ROS Production Rate in Ageing Cell Populations Conor Lawless1,2, Diana Jurk2,3, Colin S. Gillespie2,4, Daryl Shanley2,3, Gabriele Saretzki2,3, Thomas von 2,3 ˜ 2,3 Zglinicki , Joao F. Passos * 1 Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom, 2 Centre for Integrated Systems Biology of Ageing and Nutrition, Newcastle University, Newcastle-upon-Tyne, United Kingdom, 3 Institute for Ageing and Health, Newcastle University, Newcastle-upon-Tyne, United Kingdom, 4 School of Mathematics Statistics, Newcastle University, Newcastle-upon-Tyne, United Kingdom Abstract Increases in cellular Reactive Oxygen Species (ROS) concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells. One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage). However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS