After Saccharomyces cerevisiae cells cultured in a medium with glucose consume glucose, the sub-populations of quiescent and non-quiescent cells develop in the budding yeast culture. An age-related chronology of quiescent and non-quiescent yeast cells within this culture is discussed here. We also describe various hallmarks of quiescent and non-quiescent yeast cells. A complex aging-associated program underlies cellular quiescence in budding yeast. This quiescence program includes a cascade of consecutive cellular events orchestrated by an intricate signaling network. We examine here how caloric restriction, a low-calorie diet that extends lifespan and healthspan in yeast and other eukaryotes, influences the cellular quiescence program in S. cerevisiae. One of the main objectives of this review is to stimulate an exploration of the mechanisms that link cellular quiescence to chronological aging of budding yeast. Yeast chronological aging is defined by the length of time during which a yeast cell remains viable after its growth and division are arrested, and it becomes quiescent. We propose a hypothesis on how caloric restriction can slow chronological aging of S. cerevisiae by altering the chronology and properties of quiescent cells. Our hypothesis posits that caloric restriction delays yeast chronological aging by targeting four different processes within quiescent cells.

In a quest for previously unknown geroprotective natural chemicals, we used a robust cell viability assay to search for commercially available plant extracts that can substantially prolong the chronological lifespan of budding yeast. Many of these plant extracts have been used in traditional Chinese and other herbal medicines or the Mediterranean and other customary diets. Our search led to a discovery of fifteen plant extracts that significantly extend the longevity of chronologically aging yeast not limited in calorie supply. We show that each of these longevity-extending plant extracts is a geroprotector that decreases the rate of yeast chronological aging and promotes a hormetic stress response. We also show that each of the fifteen geroprotective plant extracts mimics the longevity-extending, stress-protecting, metabolic and physiological effects of a caloric restriction diet but if added to yeast cultured under non-caloric restriction conditions. We provide evidence that the fifteen geroprotective plant extracts exhibit partially overlapping effects on a distinct set of longevity-defining cellular processes. These effects include a rise in coupled mitochondrial respiration, an altered age-related chronology of changes in reactive oxygen species abundance, protection of cellular macromolecules from oxidative damage, and an age-related increase in the resistance to long-term oxidative and thermal stresses.

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 subpopulations of different buoyant densities. Process 1 of the proposed mechanism consists of a cell-cycle arrest in the G 1 phase and leads to the formation of highdensity 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.