RT Journal Article
SR Electronic
T1 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
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaba1306
DO 10.1126/sciadv.aba1306
VO 6
IS 32
A1 Zou, Ke
A1 Rouskin, Silvia
A1 Dervishi, Kevin
A1 McCormick, Mark A.
A1 Sasikumar, Arjun
A1 Deng, Changhui
A1 Chen, Zhibing
A1 Kaeberlein, Matt
A1 Brem, Rachel B.
A1 Polymenis, Michael
A1 Kennedy, Brian K.
A1 Weissman, Jonathan S.
A1 Zheng, Jiashun
A1 Ouyang, Qi
A1 Li, Hao
YR 2020
UL http://advances.sciencemag.org/content/6/32/eaba1306.abstract
AB 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.