Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses
Figure 3
Simulations of a positive feedback-loop motif.
A rule-based fuzzy-logic computation shows dynamical changes of age-related alterations in the Vicious Cycle (VC) model as shown in Figure 2. The main characteristic of the simulation outcome is a steep increase in free radicals (ROS) and oxidized proteins due to an amplifying positive feedback, since ROS damages mitochondrial DNA and mitochondrial proteins, impairing the ability to produce ATP, which leads to an increase in ADP levels. Accordingly, mitochondrial respiration and biosynthesis decline exponentially with age. Also provided is the total accumulated energy turnover, which is leveling off with age due to reduced metabolism. High levels of free radical concentrations and protein oxidation are not viable and may lead to cell apoptosis. The end of cellular lifespan is defined here and in all subsequent simulations when oxidized proteins exceeds a 0.4 level, data beyond this point are still shown in shaded areas until ATP consumption reaches zero.