Ana L. Santos
Ariel B. Lindner
Keywords: ageing, life-history evolution, microfluidics, stress response, Gompertz law
Ageing can be viewed as the removal of functional redundancies from complex systems by the inevitable decay of their components. The population distributions of lifespans and their hazard functions can be used as indicators of the characteristics and timescales of the ageing process. We decided to empirically measure the lifespan distributions of wild-type and selected single-gene deletion mutants of Escherichia coli in carbon starvation. This is only possible by monitoring large populations of individually isolated and environmentally controlled isogenic cells in microfluidic devices. Not unlike in higher animals, individuals die in qualitatively different manners at different times. Lifespan distributions could be modeled by the generalized extreme value distributions, including Weibull and Gompertz. Some mutants follow Weibull distributions where hazard functions increase in polynomial terms with age.
However most strains including the wild-type follow Gompertz distributions where hazard functions increase exponentially. The coefficients of this exponential increase, defined as the ageing rate, remain constant for most strains, despite their different initial mortality rates & average lifespans. We are also able identified a few pathways, whose mutants significantly lower ageing rates. One of them is the general stress response pathway controlled by stationary-phase sigma factor RpoS, which is activated by starvation.
With a simple toy model of proteome sectors, we showed that the rpoS pathway mediates the resource trade-offs between immediate needs and long-term preservation of viability in starvation. This finding connects the abstract evolutionary theories of ageing to a central genetic pathway in a well-studied model organism, explaining some known paradoxes of its evolution.
Publication and deliverables
Yang, Y., Song, X. & Lindner, A. B. Time-lapse microscopy and image analysis of Escherichia coli cells in mother machines, vol. 43 of Methods in Microbiology, chap. 2, 49-68 (Elsevier, 2016).
Yang, Y. Escherichia coli general stress response delays aging in adaptation to feast-or-famine life history. Doctoral thesis, Paris Descartes University (2016).