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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.

Ke ZouSilvia RouskinKevin DervishiMark A McCormickArjun SasikumarChanghui DengMatt KaeberleinRachel B BremMichael PolymenisBrian Keith KennedyJonathan S WeissmanJiashun ZhengQi OuyangHao Li
Published in: Science advances (2020)
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.
Keyphrases
  • single cell
  • rna seq
  • amino acid
  • blood glucose
  • type diabetes
  • gene expression
  • transcription factor
  • skeletal muscle
  • dna methylation
  • dendritic cells