title: Availability of Amino Acids Extends Chronological Lifespan by Suppressing Hyper-Acidification of the Environment in Saccharomyces cerevisiae.
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.
authors.affiliation: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Inage-ku, Chiba, 263-8522, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Maruyama
authors.affiliation: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Inage-ku, Chiba, 263-8522, Japan.|Keiyo Plant Engineering Co., Ltd., 2-8-8 Ichikawaminami, Ichikawa, Chiba, 272-0032, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Inage-ku, Chiba, 263-8522, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kodama
authors.affiliation: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Inage-ku, Chiba, 263-8522, Japan.|Molecular Chirality Research Center, Chiba University, Inage-ku, Chiba, 263-8522, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuura
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D016922:Cellular Senescence / Q000187:drug effects; D003470:Culture Media; D006863:Hydrogen-Ion Concentration; D008136:Longevity / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000596:Amino Acids; D003470:Culture Media; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors