Dynamic Modelling of Pathways to Cellular Senescence Reveals Strategies for Targeted Interventions
Figure 7
Sensitivity analysis at 1, 10 and 20 days post-irradiation indicated three states of cellular senescence: early, middle and late senescence. Sensitivity analysis was computed for the model species (y axis) upon perturbation of the kinetic rate constant parameters (x axis). The parameters k1–k11 are involved in the IIS-TOR signalling sub-network, whereas the groups of parameters k12–k32 and k33–k41 regulate the DDR-ROS signalling response and mitochondrial dynamics, respectively. Model species sensitivities changed over time, highlighting a dysfunction for mitophagy and mitochondria, and DDR-ROS stress-response at the later time points. These dysregulations consolidated over time and ultimately attenuated the global sensitivity in the model. Scale bar represents the normalised positive or negative sensitivity of each species to each rate constant.
