Abstract
The chronological lifespan of Saccharomyces cerevisiae represents the duration of cell survival in the postdiauxic and stationary phases. Using a prototrophic strain derived from the standard auxotrophic laboratory strain BY4742, we showed that supplementation of non-essential amino acids to a synthetic defined (SD) medium increases maximal cell growth and extends the chronological lifespan. The positive effects of amino acids can be reproduced by modulating the medium pH, indicating that amino acids contribute to chronological longevity in a cell-extrinsic manner by alleviating medium acidification. In addition, we showed that the amino acid-mediated effects on extension of chronological longevity are independent of those achieved through a reduction in the TORC1 pathway, which is mediated in a cell-intrinsic manner. Since previous studies showed that extracellular acidification causes mitochondrial dysfunction and leads to cell death, our results provide a path to premature chronological aging caused by differences in available nitrogen sources. Moreover, acidification of culture medium is generally associated with culture duration and cell density; thus, further studies are required on cell physiology of auxotrophic yeast strains during the stationary phase because an insufficient supply of essential amino acids may cause alterations in environmental conditions.
Highlights
All living organisms are subjected to physiological decline with age, which restricts the lifespan of the organism
A previous study showed that concentrations of supplemented amino acids in synthetic complete (SC) medium affected growth and glucose consumption of auxotrophic yeast cells and concluded that limitation of essential amino acids leads to early growth arrest and short chronological lifespan [13]
The positive role of essential amino acids in the chronological lifespan of auxotrophic yeast cells has been established, an earlier study showed that non-essential amino acids had negative effects on the replicative lifespan of auxotrophic cells [12]
Summary
All living organisms are subjected to physiological decline with age, which restricts the lifespan of the organism. Recent advances by studies on the mechanisms of aging have revealed many causal factors, including oxidative stress, telomere shortening, mitochondrial dysfunction, epigenetic changes and loss of protein quality control. The primary causes of aging, if any, remain controversial. Availability of Amino Acids Relieves Acidification of the Medium in Budding Yeast development, or marketed products, etc. This commercial funder did not alter the authors' adherence to PLOS ONE policies on sharing data and materials
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