Demographic Consequences of Damage Dynamics in Single-Cell Ageing

Abstract

Ageing is driven by the accumulation of diverse types of damage that leads to a decline in function over time. In unicellular organisms, in addition to this damage accumulation within individuals, asymmetric partitioning of damage at cell division might also play a crucial role in shaping demographic ageing patterns. Despite empirical single-cell studies providing quantitative data at the molecular and demographic level, a comprehensive understanding of how cellular damage production and partition propagate and influence demographic patterns is still lacking. To address this gap, we present a generic and flexible damage model using a stochastic differential equation approach which incorporates stochastic damage accumulation and asymmetric damage partitioning at cell divisions. We provide an analytical approximation linking cellular and damage parameters to demographic ageing patterns. Interestingly, we observe that the lifespan of the cells follows an inverse-gaussian distribution whose statistical properties can be expressed with cellular and damage parameters, as well as easily inferred from empirical single-cell data. Furthermore, we demonstrate how stochasticity (noise) in damage production and asymmetry in damage partitioning contribute to shaping lifespans. Applying the model to empiricalE.colidata reveals non-exponential scaling in mortality rates, which cannot be captured by classical Gompertz-Makeham models. Additionally, we highlight the essential role of stochastic division times in shaping lifespans. Our findings provide a deeper understanding of how fundamental processes contribute to cellular damage dynamics and generate demographic patterns. The generic nature and flexibility of our damage model offer a valuable framework for investigating ageing in diverse biological systems.