Aging and the Survival of Quiescent and Non-quiescent Cells in Yeast Stationary-Phase Cultures

Abstract

In this chapter, we argue that with careful attention to cell types in stationary-phase cultures of the yeast, S. cerevisiae provide an excellent model system for aging studies and hold much promise in pinpointing the set of causal genes and mechanisms driving aging. Importantly, a more detailed understanding of aging in this single celled organism will also shed light on aging in tissue-complex model organisms such as C. elegans and D. melanogaster. We feel strongly that the relationship between aging in yeast and tissue-complex organisms has been obscured by failure to notice the heterogeneity of stationary-phase cultures and the processes by which distinct cell types arise in these cultures. Although several studies have used yeast stationary-phase cultures for chronological aging, the majority of these studies have assumed that cultures in stationary phase are homogeneously composed of a single cell type. However, genome-scale analyses of yeast stationary-phase cultures have identified two major cell fractions: quiescent and non-quiescent, which we discuss in detail in this chapter. We review evidence that cell populations isolated from these cultures exhibit population-specific phenotypes spanning a range of metabolic and physiological processes including reproductive capacity, apoptosis, differences in metabolic activities, genetic hyper-mutability, and stress responses. The identification, in S. cerevisiae, of multiple sub-populations having differentiated physiological attributes relevant to aging offers an unprecedented opportunity. This opportunity to deeply understand yeast cellular (and population) aging programs will, also, give insight into genomic and metabolic processes in tissue-complex organism, as well as stem cell biology and the origins of differentiation.

Sphingolipids and lifespan regulation

“…RLS is a measure of how many times a cell can bud to give rise to a new cell, while the other measure of yeast lifespan, chronological lifespan (CLS), is a measure of how long cells survive after they have stopped dividing and entered a quiescent or G o state [25] that yeast researchers term stationary phase [26]. Stationary phase populations contain long-lived quiescent cells that can enter the cell division cycle, and non-quiescent cells that are short-lived and cannot enter the cell division cycle, similar to the phenotype of senescent mammalian cells.…”

Uncoupling reproduction from metabolism extends chronological lifespan in yeast

“…Quiescent cells consist primarily of daughter cells that have never budded, possess high stress tolerance, and retain high viability during prolonged periods of starvation (82). These cells seem poised to resume growth when resupplied with nutrients.…”

“…However, whereas quiescent yeast meets minimum energy requirements via respiration, encapsulated yeast is highly fermentative. Both quiescent and encapsulated cell types possess certain characteristics of metazoan cells, with quiescent cells being similar to stem cells (82) and wellfed encapsulated cells being similar to postmitotic cells that are terminally differentiated.…”

Similar environments but diverse fates: Responses of budding yeast to nutrient deprivation

“…Sporulation occurs under the specific condition of active respiration (NFCs being much higher than FCs), high pH, and depleted nitrogen and/or other nutrients (reviewed in 156157). Quiescence, like sporulation, is triggered by the absence of at least one essential growth nutrient and alkaline pH, but (unlike sporulation) quiescence does not have a requirement for respiration (reviewed in 10158. Finally, pseudohyphal differentiation occurs at intermediate-to-low nitrogen concentrations (reviewed in 135), can also be induced by other cues such as fusel alcohols, and also responds to other cues in some strain backgrounds (reviewed in 159).…”