Modelling the Dynamics of Senescence Spread

Cellular senescence is a cell surveillance mechanism that arrests the cell cycle
in damaged cells. The senescent phenotype can spread from cell to cell through
paracrine and juxtacrine signalling, but the dynamics of this process are not well
understood. Although senescent cells are important in ageing, wound healing,
and cancer, it is unclear how the spread of senescence is contained in senescent
lesions. In the absence of the immune system, senescence could theoretically
spread infinitely from one cell to another, but this contradicts experimental
evidence. To investigate this issue, we developed both a minimal mathematical
model and a stochastic simulation of senescence spread. Our results suggest that
differences in the number of signalling molecules secreted between subtypes of
senescent cells can limit the spread of senescence. We found that dynamic, timedependent paracrine signalling prevents the uncontrolled spread of senescence
and we demonstrate how model parameters can be determined using Bayesian
inference in a proposed experiment.