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Lookup NU author(s): Dr Conor LawlessORCiD, Dr Diana Jurk, Dr Colin GillespieORCiD, Dr Daryl Shanley, Dr Gabriele Saretzki, Professor Thomas von Zglinicki, Dr Joao Passos
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 concentration: the Stochastic Step Model of Replicative Senescence (SSMRS). We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.
Author(s): Lawless C, Jurk D, Gillespie CS, Shanley D, Saretzki G, von Zglinicki T, Passos JF
Publication type: Article
Publication status: Published
Journal: PLoS One
Year: 2012
Volume: 7
Issue: 2
Print publication date: 16/02/2012
Date deposited: 19/03/2012
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: http://dx.doi.org/10.1371/journal.pone.0032117
DOI: 10.1371/journal.pone.0032117
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