Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses
Figure 9
Sensitivity analysis of NF-κB.
In this analysis the sensitivity of NF-κB is modified between +/−5 and +/−20%, and by +100% and −50%. The NF-κB activity is plotted over the course of lifespan as recorded by simulation runs compared to a baseline (black) from model predictions shown in Figure 6. End of lifespan is reached when the level of oxidized proteins reaches 0.4 as indicated. A second fitness criterion indicates ATP consumption levels at a 0.4 threshold (dotted magenta line). Substantial differences in NF-κB activity are observed around midlife but converge later without affecting overall lifespan. Substantial reduction in lifespan is only seen at very low NF-κB values along with damage related low levels of ATP consumption.