4.8 Article

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

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SCIENCE ADVANCES
卷 6, 期 32, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aba1306

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  1. NIH [R01AG058742, R01AG043080, R21AG060129, P30AG013280, GM123139, P20GM121176]
  2. National Science Foundation of China [NSFC 11434001, 11774011]
  3. American Federation for Aging Research Junior Faculty Grant

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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.

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