Water-Transfer Slows Aging in Saccharomyces cerevisiae

Abstract

Transferring Saccharomyces cerevisiae cells to water is known to extend their lifespan. However, it is unclear whether this lifespan extension is due to slowing the aging process or merely keeping old yeast alive. Here we show that in water-transferred yeast, the toxicity of polyQ proteins is decreased and the aging biomarker 47Q aggregates at a reduced rate and to a lesser extent. These beneficial effects of water-transfer could not be reproduced by diluting the growth medium and depended on de novo protein synthesis and proteasomes levels. Interestingly, we found that upon water-transfer 27 proteins are downregulated, 4 proteins are upregulated and 81 proteins change their intracellular localization, hinting at an active genetic program enabling the lifespan extension. Furthermore, the aging-related deterioration of the heat shock response (HSR), the unfolded protein response (UPR) and the endoplasmic reticulum-associated protein degradation (ERAD), was largely prevented in water-transferred yeast, as the activities of these proteostatic network pathways remained nearly as robust as in young yeast. The characteristics of young yeast that are actively maintained upon water-transfer indicate that the extended lifespan is the outcome of slowing the rate of the aging process.

Stability of Dry and Liquid Metschnikowia pulcherrima Formulations for Biocontrol Applications against Apple Postharvest Diseases

“…Survival and cell viability in water have been studied extensively in the context of aging, life span extension, and calorie restriction in Saccharomyces cerevisiae: Transferring S. cerevisiae cells to water stops growth, slows aging, and dramatically increases life span [47][48][49][50][51][52][53][54]. This phenomenon likely explains the long-term survival of M. pulcherrima in the liquid formulations tested here.…”

Self-Generated Hypoxia Leads to Oxidative Stress and Massive Death in Ustilago maydis Populations under Extreme Starvation and Oxygen-Limited Conditions

“…Thus, as we began to analyze the phenomenon more systematically, it soon became clear that the central underpinning point of difference between the water-transferred stationary phase U. maydis and S. cerevisiae cells, simply lies in the fact that U. maydis cells are metabolically active in water and that the fungus respires, i.e., that it consumes oxygen. Compared to the behavior of S. cerevisiae whose response to water transfer is characterized by a highly reduced metabolic activity (an energy preservation mode) and by an extended lifespan [ 1 , 27 ], the observation that U. maydis is metabolically active even when incubated in pure water seems rather curious. However, we are not in a position to comment further upon this intriguing finding, except to point out that a more comprehensive understanding of the overall “terrain” of U. maydis water-transfer physiology is needed, before the biological meaning of the differences between these two fungi can be grasped better.…”

“…These environmental variables include a wide spectrum of factors, ranging from the fluctuations in the types and quantities of available nutrients through the occurrence of adverse conditions such as elevated temperatures, desiccation, flooding, high-osmolarity, acidity, etc., to the presence of very pernicious agents that are different forms of irradiation and toxic compounds. Within this remarkable range of factors, nutrient starvation might well be the most common stress experienced by microorganisms in their natural habitats, and many excellent lab-studies were done exploring this problem within different conceptual and experimental frameworks, including the most extreme form of starvation, namely “water-transfer” [ 1 ]—a term used to refer to the transfer of cells from a growth medium to pure water.…”

“…It was also demonstrated that autophagy is upregulated in water-transferred yeast, and that it is required for chronological lifespan extension, upon transfer [ 7 ]. Furthermore, the maintenance of cell viability under this extreme starvation is also dependent on proteasomes and on the ongoing protein synthesis of a limited set of, presumably, the most essential proteins [ 1 ]. Generally, this same study revealed that in response to water-transfer, yeast cells mount a complex response that, through certain reorganizations of the intracellular milieu, results in a prolonged lifespan, by maintaining the characteristics of young yeast.…”

“…Generally, this same study revealed that in response to water-transfer, yeast cells mount a complex response that, through certain reorganizations of the intracellular milieu, results in a prolonged lifespan, by maintaining the characteristics of young yeast. In any case, yeast cells stop dividing immediately upon water-transfer [ 1 ]. However, it should be recalled that if the water-transferred yeast cells are incubated in the presence of either fermentable or non-fermentable sugars, morphological and physiological changes characteristic of mitotically growing cells are induced, causing a drastic loss of viability within a few hours [ 2 , 3 ].…”