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.
Highlights
Increased human life expectancy, with its impact on aging and age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases, drives extensive ongoing aging research [1]
Yeast viability may be assessed by using the nucleus staining dye propidium iodide (PI), which allows calculating the percentage of live and dead cells in a given population [23]
We found that CHX eliminated the difference in 47Q aggregation between cells transferred to water or those maintained in synthetic complete (SC), yielding Aggregation Index with intermediary values, i.e., lower than in cells maintained in SC but higher than in water-transferred cells (Fig 5B)
Summary
With its impact on aging and age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases, drives extensive ongoing aging research [1]. Recent aging research is mainly advanced by uncovering aging-related genetic and biochemical pathways that are conserved in evolution and may modify the rate and progression of the aging process [3]. Wide gaps exist in our understanding of aging, when it begins, what drives it, and which biological aspects are affected [4]. This is because multiple and diverse processes affect, and are impacted by, aging. Various approaches must be taken in studying biological aging [5]. Hayflick's discovery that cells senesce and stop dividing after a PLOS ONE | DOI:10.1371/journal.pone.0148650 February 10, 2016
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