Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan,Cell

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Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
Cell ( IF 64.5 ) Pub Date : 2023-01-05 , DOI: 10.1016/j.cell.2022.12.007
Clara Correia-Melo ₁ , Stephan Kamrad ₂ , Roland Tengölics ₃ , Christoph B Messner ₄ , Pauline Trebulle ₅ , StJohn Townsend ₆ , Sreejith Jayasree Varma ₇ , Anja Freiwald ₈ , Benjamin M Heineike ₉ , Kate Campbell ₁₀ , Lucía Herrera-Dominguez ₂ , Simran Kaur Aulakh ₅ , Lukasz Szyrwiel ₆ , Jason S L Yu ₂ , Aleksej Zelezniak ₁₁ , Vadim Demichev ₁ , Michael Mülleder ₁₂ , Balázs Papp ₃ , Mohammad Tauqeer Alam ₁₃ , Markus Ralser ₁₄

Affiliation

The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK; Department of Biochemistry, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged 6726, Hungary; HCEMM-BRC Metabolic Systems Biology Lab, Szeged 6726, Hungary.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Precision Proteomics Center, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, Switzerland.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Biochemistry, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Department of Biochemistry, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Department of Biochemistry, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; Core Facility - High Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Quantitative Gene Expression Research Group, MRC London Institute of Medical Sciences (LMS), London W12 0HS, UK; Quantitative Gene Expression Research Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London SW2 2AZ, UK.
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden; Randall Centre for Cell & Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK; Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius 10257, Lithuania.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK; Core Facility - High Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Department of Biology, College of Science, United Arab Emirates University, P.O.Box 15551, Al-Ain, United Arab Emirates.
The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK; Department of Biochemistry, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.

Metabolism is deeply intertwined with aging. Effects of metabolic interventions on aging have been explained with intracellular metabolism, growth control, and signaling. Studying chronological aging in yeast, we reveal a so far overlooked metabolic property that influences aging via the exchange of metabolites. We observed that metabolites exported by young cells are re-imported by chronologically aging cells, resulting in cross-generational metabolic interactions. Then, we used self-establishing metabolically cooperating communities (SeMeCo) as a tool to increase metabolite exchange and observed significant lifespan extensions. The longevity of the SeMeCo was attributable to metabolic reconfigurations in methionine consumer cells. These obtained a more glycolytic metabolism and increased the export of protective metabolites that in turn extended the lifespan of cells that supplied them with methionine. Our results establish metabolite exchange interactions as a determinant of cellular aging and show that metabolically cooperating cells can shape the metabolic environment to extend their lifespan.

中文翻译：

细胞间代谢物交换创造了有利于生存的代谢环境，延长了寿命

新陈代谢与衰老密切相关。代谢干预对衰老的影响已通过细胞内代谢、生长控制和信号传导来解释。通过研究酵母的时间老化，我们揭示了一种迄今为止被忽视的代谢特性，它通过代谢物的交换影响衰老。我们观察到，年轻细胞输出的代谢物被按时间顺序老化的细胞重新输入，从而导致跨代代谢相互作用。然后，我们使用自建代谢合作群落 (SeMeCo) 作为增加代谢物交换的工具，并观察到寿命显着延长。 SeMeCo 的长寿归因于蛋氨酸消耗细胞的代谢重新配置。它们获得了更多的糖酵解代谢，并增加了保护性代谢物的输出，从而延长了为它们提供蛋氨酸的细胞的寿命。我们的结果将代谢物交换相互作用确定为细胞衰老的决定因素，并表明代谢协作的细胞可以塑造代谢环境以延长其寿命。

更新日期：2023-01-05

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