Diverse geroprotectors differently affect a mechanism linking cellular aging to cellular quiescence in budding yeast.

We propose a hypothesis of a mechanism linking cellular aging to cellular quiescence in chronologically aging budding yeast. Our hypothesis posits that this mechanism integrates four different processes, all of which are initiated after yeast cells cultured in a medium initially containing glucose consume it. Quiescent cells that develop in these cultures can be separated into the high- and low-density sub-populations of different buoyant densities. Process 1 of the proposed mechanism consists of a cell-cycle arrest in the G phase and leads to the formation of high-density quiescent cells. Process 2 results in converting high-density quiescent cells into low-density quiescent cells. Processes 3 and 4 cause a fast or slow decline in the quiescence of low- or high-density quiescent cells, respectively. Here, we tested our hypothesis by assessing how four different geroprotectors influence the four processes that could link cellular aging to cellular quiescence. We found that these geroprotectors differently affect processes 1 and 2 and decelerate processes 3 and 4. We also found that a rise in trehalose within quiescent yeast contributes to chronological aging and quiescence maintenance. These data collectively provide conclusive evidence for a mechanistic link between cellular aging and cellular quiescence.