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. Academic Article uri icon


  • 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.

published proceedings

  • Sci Adv

altmetric score

  • 142.958

author list (cited authors)

  • Zou, K. e., Rouskin, S., Dervishi, K., McCormick, M. A., Sasikumar, A., Deng, C., ... Li, H.

citation count

  • 18

complete list of authors

  • Zou, Ke||Rouskin, Silvia||Dervishi, Kevin||McCormick, Mark A||Sasikumar, Arjun||Deng, Changhui||Chen, Zhibing||Kaeberlein, Matt||Brem, Rachel B||Polymenis, Michael||Kennedy, Brian K||Weissman, Jonathan S||Zheng, Jiashun||Ouyang, Qi||Li, Hao

publication date

  • August 2020