Based on the recent findings of the Titorenko laboratory, I hypothesized that caloric restriction slows the chronological aging of budding yeast Saccharomyces cerevisiae because this geroprotective dietary intervention is integrated into the four processes of a cellular quiescence program. Limitation of calories prolongs yeast longevity by altering the properties of quiescent cells through an intricate network of nutrient-signaling pathways. In addition, I propose that genetic interventions inferring mutations in the Target of Rapamycin Complex 1 (TORC1)-Serine/threonine-protein kinase (Sch9) nutrient signaling branch (such as the tor1Δ and sch9Δ mutations) display longevity-extending phenotypes as a caloric restriction by targeting the processes of the quiescence program. In this study, caloric restriction and the mutant phenotypes of sch9 (in some cells) demonstrated a deceleration of yeast chronological aging by arresting the cell cycle in early G1 and stimulating the development of high-density quiescent cells (process 1), whereas the phenotypes of the tor1 and the sch9 mutants (in some cells) displayed cell cycle arrest in late G1, developing high-density quiescent cells. Caloric restriction promoted an aging-associated conversion of high-density quiescent cells into low-density quiescent cells (process 2), while the phenotypes of the tor1 and the sch9 mutants (in some cells) postponed the conversion of high-density quiescent cells into low-density quiescent cells. Therefore, yeast longevity can be extended by either promoting or decelerating process 2 of the quiescence program. The three interventions displayed a common effect in which they slowed down a fast aging-associated deterioration in clonogenicity of low-density quiescent cells (process 3) and postponed a slow aging-associated decline in clonogenicity of high-density quiescent cells (process 4)
