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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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.
author list (cited authors)
Zou, K. e., Rouskin, S., Dervishi, K., McCormick, M. A., Sasikumar, A., Deng, C., ... Li, H.
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