Monitoring the transition to replicative senescence in single yeast cells

Aging is an intrinsic feature of living organisms, which is partly genetically determined. In budding yeast, a mother cell can produce a limited number of daughter cells before it enters senescence. Over the last fifteen years, budding yeast has emerged as a compelling organism in which to investigate the genetic mechanisms that regulate longevity. Yet a precise and quantitative understanding of the transition to replicative senescence is still missing, in part because of the lack of techniques to monitor age-induced cellular processes over a long enough period of time. We have developed a new microfluidics technique to track the successive divisions of single yeast cells from birth to death under the microscope. Using this methodology, we have started to characterize the transition to replicative senescence in a quantitative manner using custom data analysis. Our data reveal that aging cells experience a large variability in cell cycle durations and undergo stochastic and partially reversible cell cycle "crises" that coincide with the induction of stress response. Therefore, in contrary to the current cellular aging paradigm that describes aging as a progressive accumulation of damages, our preliminary results reveal and highlighted the dynamic nature of the transition to senescence.