"Modelling the spread of senescence"Martin, LucyCellular 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 (secreted protein) and juxtacrine (cell contact) 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, time-dependent paracrine signalling prevents the uncontrolled spread of senescence and we demonstrate how model parameters can be determined using Bayesian inference in a proposed experiment. |
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