PMID- 32821821 OWN - NLM STAT- MEDLINE DCOM- 20220411 LR - 20230829 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 6 IP - 32 DP - 2020 Aug TI - 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. PG - eaba1306 LID - 10.1126/sciadv.aba1306 [doi] LID - eaba1306 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. CI - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). FAU - Zou, Ke AU - Zou K AUID- ORCID: 0000-0003-4860-4439 AD - Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. AD - The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China. AD - Peking-Tsinghua Center for Life Sciences at Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. FAU - Rouskin, Silvia AU - Rouskin S AUID- ORCID: 0000-0003-2042-6642 AD - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California Institute for Quantitative Biomedical Research and Howard Hughes Medical Institute, San Francisco, CA 94158, USA. FAU - Dervishi, Kevin AU - Dervishi K AD - Harvard Medical School, Boston, MA 02115, USA. FAU - McCormick, Mark A AU - McCormick MA AD - Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. AD - Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, Albuquerque, NM 87131, USA. FAU - Sasikumar, Arjun AU - Sasikumar A AD - Buck Institute for Research on Aging, Novato, CA 94945, USA. FAU - Deng, Changhui AU - Deng C AD - Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. FAU - Chen, Zhibing AU - Chen Z AUID- ORCID: 0000-0003-4860-4439 AD - Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, San Francisco, CA 94158, USA. FAU - Kaeberlein, Matt AU - Kaeberlein M AUID- ORCID: 0000-0002-1311-3421 AD - Department of Pathology, University of Washington, Seattle, WA 98195, USA. FAU - Brem, Rachel B AU - Brem RB AUID- ORCID: 0000-0002-8587-9434 AD - Buck Institute for Research on Aging, Novato, CA 94945, USA. FAU - Polymenis, Michael AU - Polymenis M AUID- ORCID: 0000-0003-1507-0936 AD - Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA. FAU - Kennedy, Brian K AU - Kennedy BK AUID- ORCID: 0000-0002-5754-1874 AD - Buck Institute for Research on Aging, Novato, CA 94945, USA. AD - Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Centre for Healthy Longevity, National University Health System, Singapore. AD - Singapore Institute for Clinical Sciences, ASTAR, Singapore. FAU - Weissman, Jonathan S AU - Weissman JS AUID- ORCID: 0000-0003-2445-670X AD - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California Institute for Quantitative Biomedical Research and Howard Hughes Medical Institute, San Francisco, CA 94158, USA. FAU - Zheng, Jiashun AU - Zheng J AUID- ORCID: 0000-0003-3266-4461 AD - Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. FAU - Ouyang, Qi AU - Ouyang Q AUID- ORCID: 0000-0003-1585-7368 AD - The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China. AD - Peking-Tsinghua Center for Life Sciences at Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. FAU - Li, Hao AU - Li H AUID- ORCID: 0000-0003-4889-953X AD - Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. LA - eng GR - R01 GM123139/GM/NIGMS NIH HHS/United States GR - R21 AG060129/AG/NIA NIH HHS/United States GR - P01 AG001751/AG/NIA NIH HHS/United States GR - P20 GM121176/GM/NIGMS NIH HHS/United States GR - R01 AG043080/AG/NIA NIH HHS/United States GR - P30 AG013280/AG/NIA NIH HHS/United States GR - R01 AG058742/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200805 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - AE28F7PNPL (Methionine) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Dietary Supplements MH - Glucose/pharmacology MH - *Longevity MH - *Methionine MH - Saccharomyces cerevisiae/genetics PMC - PMC7406366 EDAT- 2020/08/22 06:00 MHDA- 2022/04/12 06:00 PMCR- 2020/08/05 CRDT- 2020/08/22 06:00 PHST- 2019/11/07 00:00 [received] PHST- 2020/06/22 00:00 [accepted] PHST- 2020/08/22 06:00 [entrez] PHST- 2020/08/22 06:00 [pubmed] PHST- 2022/04/12 06:00 [medline] PHST- 2020/08/05 00:00 [pmc-release] AID - aba1306 [pii] AID - 10.1126/sciadv.aba1306 [doi] PST - epublish SO - Sci Adv. 2020 Aug 5;6(32):eaba1306. doi: 10.1126/sciadv.aba1306. eCollection 2020 Aug.