Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses
Figure 6
Fuzzy-logic simulation of the Adaptive Response model.
In this simulation of the complete AR-model (see graph in Figure 4) concentration of reactive molecules stay constant at low levels and oxidized proteins accumulate slower increasing lifespan, different to the model predictions shown in Figures 3 and 5. In this setting, oxidized proteins become the main mechanism for activation of the stress response sensor NF-κB. Low ATP values decrease mTOR, downregulate ribosomal functions, but enhance autophagy as protecting mechanisms. The underlying alterations in gene transcription and translation decrease mitochondrial respiration but upregulate aerobic glycolysis, which becomes a major contributing factor to energy supply towards the end of lifespan. The overall accumulated energy turnover is higher compared to all other models. The AR model demonstrates an earlier onset and more linear rates of decline for energy related parameters if compared to the aging phenotype predicted by the Vicious Cycle model.