Characterizing the effect of chronological aging on the dynamics of catabolite repression

Although aging is one of the most prominent biological processes, our knowledge about the effect of aging on metabolic pathways and cellular responses to environments with changing nutrients is still limited. Coping with these questions requires studying not only the impact of the environment on mortality but also on the performances of cells as they age. The conservation of major pathways between the budding yeast, S. cerevisiae, and higher eukaryotic systems and its relatively short lifespan makes it a powerful model organism for studying aging dynamics.

We use imaging in microfluidic devices and automated flow cytometry together with mathematical modelling to characterize, at the single-cell level, dynamics of catabolite repression, how cells sense and respond to the switch from a preferred carbon source (glucose) to a less preferred one (galactose), as a function of chronological age.

We show that the response time to changes of carbon source from glucose to galactose exhibit two-phases: at young chronological ages, cells respond faster than young ones. Moreover, we show that the old cells overcome young cells as the environment changes. Analysis of mutants that lack catabolite repression does not show this age effect, suggesting that a lack of repression allows older cells to respond faster to different carbon sources. The second phase exhibits a continuous deterioration in response time. Interestingly, unlike the mortality rate, which increases with age, the slowdown rate diminishes with age. Our framework can be used for analyzing the age-phenotype in their correlation with mortality in other systems.

Supervise: Dr. Yonatan Savir