Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools

Nathaniel L. Hepowit, Jessica K. A. Macedo, Lyndsay E. A. Young, Ke Liu, Ramon C. Sun, Jason A. MacGurn, View ORCID ProfileRobert C. Dickson
doi: https://doi.org/10.1101/2020.10.30.362459
Nathaniel L. Hepowit
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jessica K. A. Macedo
2Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA
3Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lyndsay E. A. Young
2Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ke Liu
4Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, Sichuan University, Chengdu, Sichuan 610000, P. R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ramon C. Sun
3Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
5Department of Neuroscience, University of Kentucky, Lexington, KY 40536, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason A. MacGurn
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: bobd@uky.edu jason.a.macgurn@vanderbilt.edu
Robert C. Dickson
2Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Robert C. Dickson
  • For correspondence: bobd@uky.edu jason.a.macgurn@vanderbilt.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The increasing prevalence of age-related diseases and resulting healthcare insecurity and emotional burden require novel treatment approaches. Several promising strategies seek to limit nutrients and promote healthy aging. Unfortunately, the human desire to consume food means this strategy is not practical for most people but pharmacological approaches might be a viable alternative. We previously showed that myriocin, which impairs sphingolipid synthesis, increases lifespan in Saccharomyces cerevisiae by modulating signaling pathways including the target of rapamycin complex 1 (TORC1). Since TORC1 senses cellular amino acids, we analyses amino acid pools and identified 17 that are lowered by myriocin treatment. Studying the methionine transporter, Mup1, we found that newly synthesized Mup1 traffics to the plasma membrane and is stable for several hours but is inactive in drug-treated cells. Activity can be restored by adding phytosphingosine to culture medium thereby bypassing drug inhibition, thus confirming a sphingolipid requirement for Mup1 activity. Importantly, genetic analysis of myriocin-induced longevity revealed a requirement for the Gtr1/2 (mammalian Rags) and Vps34-Pib2 amino acid sensing pathways upstream of TORC1, consistent with a mechanism of action involving decreased amino acid availability. These studies demonstrate the feasibility of pharmacologically inducing a state resembling amino acid restriction to promote healthy aging.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted October 30, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools
Nathaniel L. Hepowit, Jessica K. A. Macedo, Lyndsay E. A. Young, Ke Liu, Ramon C. Sun, Jason A. MacGurn, Robert C. Dickson
bioRxiv 2020.10.30.362459; doi: https://doi.org/10.1101/2020.10.30.362459
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools
Nathaniel L. Hepowit, Jessica K. A. Macedo, Lyndsay E. A. Young, Ke Liu, Ramon C. Sun, Jason A. MacGurn, Robert C. Dickson
bioRxiv 2020.10.30.362459; doi: https://doi.org/10.1101/2020.10.30.362459

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4667)
  • Biochemistry (10332)
  • Bioengineering (7653)
  • Bioinformatics (26278)
  • Biophysics (13497)
  • Cancer Biology (10663)
  • Cell Biology (15389)
  • Clinical Trials (138)
  • Developmental Biology (8480)
  • Ecology (12800)
  • Epidemiology (2067)
  • Evolutionary Biology (16817)
  • Genetics (11378)
  • Genomics (15451)
  • Immunology (10591)
  • Microbiology (25141)
  • Molecular Biology (10187)
  • Neuroscience (54317)
  • Paleontology (399)
  • Pathology (1663)
  • Pharmacology and Toxicology (2889)
  • Physiology (4331)
  • Plant Biology (9223)
  • Scientific Communication and Education (1585)
  • Synthetic Biology (2551)
  • Systems Biology (6769)
  • Zoology (1459)