The impact of oxygen availability on yeast survival in stationary phase.

Saccharomyces cerevisiae is currently widely used as a model to study chronological aging of metazoan cells. Chronological aging is typically studied in aerobic stationary phase (SP) cultures, i.e. the final stage of batch cultures in which growth is arrested due to exogenous carbon source exhaustion. Survival of yeast cells in SP defines their chronological lifespan (CLS). S. cerevisiae SP cultures have strongly contributed to the understanding of cellular mechanisms involved in aging and indicated a key role for oxygen. Oxygen is the natural starting point for reactive oxygen species (ROS) that may both have malignant and beneficial effects on aging. In addition, oxygen allows yeast to grow on ethanol and organic acids formed during the initial respiro-fermentative growth phase on glucose. This post-diauxic phase is hallmarked by reduced growth rates, increased expression of genes involved in SP survival, and increased stress resistance. To date, the role of oxygen and respiration in aging has mostly been studied using respiratory deficient mutants, and respiration repressing agents. However, genetic or chemical interventions may result in unwanted side effects that influence survival in SP. We therefore followed a different approach to evaluate the impact of oxygen availability on yeast robustness in SP, i.e. its CLS and stress resistance, by using the capability of S. cerevisiae to grow under anaerobic conditions. A thorough physiological comparison of strictly anaerobic and aerobic SP cultures revealed that the presence of oxygen during growth and aging of S. cerevisiae strongly affects its energetic status, longevity and stress tolerance in a positive way. Combining the physiological data with genome-wide expression analysis revealed that the oxygen-dependent diauxic growth phase enabled the full induction of robustness in S. cerevisiae, and points to appropriate pre-conditioning of cells as a crucial factor to survive starvation. These findings highlight the importance of exogenous energy availability in the conditions leading to growth arrest, and bring new insight on the role of oxygen in the aging of eukaryotes.

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