Deficient ribosome biogenesis is an early marker of cellular senescence
Sandrine Morlot (IGBMC, Strasbourg)
NOTE THE NEW LOCATION (due to renovation work at LPS)
Saccharomyces cerevisiae is a powerful model organism to study replicative aging as asymmetric division gives rise to an aging mother cell and a rejuvenated daughter cell [Mortimer and Johnston 1959, Egilmez and Jazwinski 1989]. However the cellular mechanisms controlling replicative lifespan and the rejuvenation process are still poorly understood partly due to the technical limitations of following individual cells from birth to death. In this context, we have developed a high-throughput microfluidic device to follow up to 3200 single cells in parallel throughout their lifespan under the microscope. Thanks to this technology, we have established a timeline of events occurring successively during cellular aging. We have observed that cells experience a sharp transition into senescence. Indeed yeasts divide regularly every 90 minutes until a senescence entry point (SEP) which occurs after 20 generations. After this point, cell cycles strongly slow down until death [Fehrmann et al. Cell Reports 2013]. Furthermore we have measured that the SEP is preceded by an abrupt increase in the nuclear volume and more specifically in the size of nucleolus. The nucleolus is the nuclear compartment where ribosome biogenesis is initiated. This age-dependent nuclear defect is retained by the mother only, as daughter cells recover a normal nucleus and nucleolus, in agreement with the daughter cell rejuvenation paradigm. We have characterized that pre-ribosome particles accumulate in the nucleolus approximately 10 hours before entering into senescence. Our analysis suggests that this deficiency in ribosome biogenesis triggers cellular senescence.