A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism.
Autor: | Enriquez-Hesles E; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Smith DL Jr; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA; Department of Nutrition Science, Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Alabama at Birmingham, Birmingham, Alabama, USA., Maqani N; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Wierman MB; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Sutcliffe MD; Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Fine RD; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Kalita A; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Santos SM; Department of Genetics, Nutrition and Obesity Research Center, Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Alabama at Birmingham, Birmingham, Alabama, USA., Muehlbauer MJ; Department of Medicine, Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Bain JR; Department of Medicine, Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Janes KA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA; Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Hartman JL 4th; Department of Genetics, Nutrition and Obesity Research Center, Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Alabama at Birmingham, Birmingham, Alabama, USA., Hirschey MD; Department of Medicine, Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Smith JS; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA. Electronic address: jss5y@virginia.edu. |
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Jazyk: | angličtina |
Zdroj: | The Journal of biological chemistry [J Biol Chem] 2021 Jan-Jun; Vol. 296, pp. 100125. Date of Electronic Publication: 2020 Dec 02. |
DOI: | 10.1074/jbc.RA120.015402 |
Abstrakt: | Caloric restriction (CR) improves health span and life span of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging-associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological life span (CLS). We found that conditioned media collected from stationary-phase CR cultures extended CLS when supplemented into nonrestricted (NR) cultures, suggesting a potential cell-nonautonomous mechanism of CR-induced life span regulation. Chromatography and untargeted metabolomics of the conditioned media, as well as transcriptional responses associated with the longevity effect, pointed to specific amino acids enriched in the CR conditioned media (CRCM) as functional molecules, with L-serine being a particularly strong candidate. Indeed, supplementing L-serine into NR cultures extended CLS through a mechanism dependent on the one-carbon metabolism pathway, thus implicating this conserved and central metabolic hub in life span regulation. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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