Temporal scaling of ageing as an adaptive strategy of Escherichia coli

Natural selection has long been hypothesised to shape ageing patterns, but whether and how ageing contributes to life-history evolution remains elusive. The complexity of various ageing-associated molecular mechanisms and their inherent stochasticity hinder reductionist approaches to the understanding of functional senescence,i.e. reduced fecundity and increased mortality. Recent bio-demographic work demonstrated that high-precision statistics of life-history traits such as mortality rates could be used phenomenologically to understand the ageing process. We adopted this approach to study cellular senescence in growth-arrestedE. colicells, where damages to functional macromolecules are no longer diluted by fastde novobiosynthesis. We acquired high-quality longitudinal physiological and life history data of large environmentally controlled clonalE. colipopulations at single-cell resolution, using custom-designed microfluidic devices coupled to time-lapse microscopy. We show thatE. colilifespan distributions follow the Gompertz law of mortality, a century-old actuarial observation of human populations, despite developmental, cellular and genetic differences between bacteria and metazoan organisms. Measuring the shape of the hazard functions allowed us to disentangle quantitatively the demographic effects of ageing, which accumulate with time, from age-independent genetic longevity-modulating interventions. A pathway controlling cellular maintenance, the general stress response, not only promotes longevity but also temporally scales the whole distribution by reducing ageing rate. We further show thatE. coli, constrained by the amount of total biosynthesis, adapt to their natural feast-or-famine lifestyle by modulating the amount of maintenance investment, rendering ageing rate a highly evolvable life-history trait.