Figure 6. A model for the two different ways of delaying yeast chronological aging by geroprotectors that differently affect the mechanism potentially linking cellular aging to cellular quiescence.

The first way is to initiate the formation of high-density quiescent (Q) cells (process 1) by arresting the cell cycle in early G₁, speed up an age-related transition of high-density Q cells to low-density Q cells (process 2), slow down a fast aging-associated decline in the quiescence of low-density Q cells (process 3) and decelerate a slow aging-associated decline in the quiescence of high-density Q cells (process 4). Caloric restriction (CR) and the ras2Δ mutation (under non-CR conditions) postpone yeast chronological aging because they operate via the first way of targeting the mechanism that could link cellular aging to cellular quiescence. The second way is to promote the development of high-density Q cells (process 1) by arresting the cell cycle in late G₁, postpone an age-related conversion of high-density Q cells into low-density Q cells (process 2), delay a fast aging-associated decline in the quiescence of low-density Q cells (process 3) and decelerate a slow aging-associated decline in the quiescence of high-density Q cells (process 4). Lithocholic acid (LCA) and the tor1Δ mutation (both under non-CR conditions) delay yeast chronological aging because they act via the second way of targeting the mechanism potentially linking cellular aging to cellular quiescence.