(A) A tree of cell processes and cell fate decisions made by any given single cell within one simulated model update. The indicated steps are used as guideposts in the Matlab code provided in Supplementary Materials. (B). Non-linear age-dependent changes in the simulated SC pool size (upper chart, based on Abkowitz et al., 1996 and Abkowitz et al., 2002) and cell division rate (lower chart, based on Bowie et al., 2006 and Sidorov et al., 2009); the initial number of cells is 300 in simulations where the adult pool size is 10,000 cells, and proportionally larger in simulations with larger adult pool sizes. (C). Age-dependent shift in selection (somatic fitness effects of somatic driver mutations); somatic selection is explored within a range of general selection strengths (upper chart), a range of the ratio of the strength of early and late-life selection, and a range age distribution of selection directionality and strength, assumed in the MMC-DS model to be a function of physiological aging (reflecting evolved programs that determine longevity). The X-axis represents age from 0 to 100 years, as shown in panel B. The Y-axis represents a range of driver mutation fitness effects from maximum negative (-Fmax) through 1 (fitness equal to non-mutant cells) to maximum positive fitness (+Fmax). The top chart shows alteration in the general strength of selection (light blue:±Fmax = ±0.05%, dark blue:±Fmax = ±0.125%, green:±Fmax = ±0.25%, red:±Fmax = ±0.5%). The middle chart shows the simulated range of the relative strength of early-life negative to late-life positive selection (light blue: -Fmax/+Fmax = −0.5%/+0.5%, dark blue: -Fmax/+Fmax = −0.3%/+0.7%, green: -Fmax/+Fmax = −0.1%/+0.9%, red: -Fmax/+Fmax = 0%/+1%). The bottom chart demonstrates age-dependent selection shifts imposed by different aging profiles (age of selection sign switch in years: light blue – 10, dark blue – 30, green – 50, red – 70 years;±Fmax = ±0.5%).