Life span extension by glucose restriction is abrogated by methionine supplementation: Cross-talk between glucose and methionine and implication of methionine as a key regulator of life span
Open Access
- 7 August 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (32), eaba1306
- https://doi.org/10.1126/sciadv.aba1306
Abstract
Caloric restriction (CR) is known to extend life span across species; however, the molecular mechanisms are not well understood. We investigate the mechanism by which glucose restriction (GR) extends yeast replicative life span, by combining ribosome profiling and RNA-seq with microfluidic-based single-cell analysis. We discovered a cross-talk between glucose sensing and the regulation of intracellular methionine: GR down-regulated the transcription and translation of methionine biosynthetic enzymes and transporters, leading to a decreased intracellular methionine concentration; external supplementation of methionine cancels the life span extension by GR. Furthermore, genetic perturbations that decrease methionine synthesis/uptake extend life span. These observations suggest that intracellular methionine mediates the life span effects of various nutrient and genetic perturbations, and that the glucose-methionine cross-talk is a general mechanism for coordinating the nutrient status and the translation/growth of a cell. Our work also implicates proteasome as a downstream effector of the life span extension by GR.Keywords
Funding Information
- Howard Hughes Medical Institute
- NIH Office of the Director (P30AG013280)
- NIH Office of the Director (GM123139)
- NIH Office of the Director (P20GM121176)
- NIH Office of the Director (R01AG043080)
- NIH Office of the Director (R01AG058742)
- NIH Office of the Director (R21AG060129)
- American Federation for Aging Research Junior Faculty Grant
- National Science Foundation of China (11434001)
- National Science Foundation of China (11774011)
This publication has 59 references indexed in Scilit:
- Impact of caloric restriction on health and survival in rhesus monkeys from the NIA studyNature, 2012
- The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragmentsNature Protocols, 2012
- Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platformProceedings of the National Academy of Sciences of the United States of America, 2012
- Caloric Restriction Delays Disease Onset and Mortality in Rhesus MonkeysScience, 2009
- SOAP2: an improved ultrafast tool for short read alignmentBioinformatics, 2009
- Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological TargetsCell, 2009
- Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4Cell, 2008
- Genetic reconstruction of a functional transcriptional regulatory networkNature Genetics, 2007
- When transcriptome meets metabolome: fast cellular responses of yeast to sudden relief of glucose limitationMolecular Systems Biology, 2006
- Global analysis of protein localization in budding yeastNature, 2003