Figure 2.

Potential aging trajectories and systems models. A) With a “cell-cycle” model of aging, all cells move through stereotyped physiological states, but at different rates. The rate of progression through each state determines the replicative lifespan of a cell. B) In a “Waddington” model of aging, cells can move through a distinct set of physiological states that may not overlap. Both the rate of progression through states, and which physiological states an individual cell visits determines the lifespan. C) Within a “cell-cycle” model, normal cells (top) move through physiological states with certain probabilities, and interventions that increase lifespan (bottom) reduce some or all transition probabilities. D) In the “Waddington” model of aging, individual cells can proceed along different paths (top), and lifespan extending interventions might not only reduce transition probabilities, but also change which physiological states cells are likely to visit as they age (bottom).