Figure 6. Model Prediction and Validation for a Dynamic Perturbation of Aging.

(A) Single-cell state transition trajectories under 5 mM constant NAM from the data (137 cells with 104 in Path 1, 33 in Path 2) and (B) from stochastic simulations. (C) The lifespans of two aging paths under 5 mM constant NAM from experimental data (red and blue solid circles) and from simulations (red and blue curves). (D) Age-dependent state distributions of S1’, S1, S2 under 5 mM NAM. Solid circles represent the experimental data. Solid curves represent simulated results averaged from 50 simulations with shaded areas indicating standard deviation. (E) Model-predicted single-cell state transition trajectories of WT cells in response to the step input of 5 mM NAM at 9^th generation. (F) Experimental state transition trajectories of WT cells with the step input of 5 mM NAM after 600 mins, when more than 70% of cells just enter their 9^th generation. (G) The lifespans of two aging paths in response to the dynamic perturbation. Predictions: red and blue curves; Experimental data: red and blue solid circles. Dashed curves are the lifespans for no NAM treatment and constant NAM treatment. (H) Model-predicted age-dependent state distributions of S1’, S1, S2. Note the sharp increase of S1 and S2 at 10^th division (pointed by the red arrow). Solid curves are predictions averaged from 50 simulations with shaded areas indicating standard deviation. Solid circles represent the experimental data. See also Table S1.