Modelling the dynamics of senescence spread.
Aging Cell
; 22(8): e13892, 2023 08.
Article
in En
| MEDLINE
| ID: mdl-37288475
ABSTRACT
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, 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cellular Senescence
/
Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Aging Cell
Year:
2023
Document type:
Article
Affiliation country:
United kingdom