Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
Journal article, 2023
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.
metabolic microenvironment
chronological aging
eukaryotic longevity
metabolite exchange interactions
Author
Clara Correia-Melo
University of Cambridge
Charité University Medicine Berlin
The Francis Crick Institute
Stephan Kamrad
The Francis Crick Institute
Roland Tengölics
Hungarian Academy of Sciences
Christoph B. Messner
The Francis Crick Institute
University of Zürich
Pauline Trebulle
The Francis Crick Institute
University of Oxford
St John Townsend
Charité University Medicine Berlin
The Francis Crick Institute
Sreejith Jayasree Varma
Charité University Medicine Berlin
Anja Freiwald
Charité University Medicine Berlin
Benjamin M. Heineike
University of Oxford
Department of Metabolism
Medical Research Council
The Francis Crick Institute
Kate Campbell
University of Cambridge
Lucia Herrera-Dominguez
The Francis Crick Institute
Simran Kaur Aulakh
The Francis Crick Institute
University of Oxford
Lukasz Szyrwiel
Charité University Medicine Berlin
The Francis Crick Institute
Jason S.L. Yu
The Francis Crick Institute
Aleksej Zelezniak
Vilnius University
Faculty of Life Sciences & Medicine
The Francis Crick Institute
Chalmers, Life Sciences, Systems and Synthetic Biology
Vadim Demichev
Charité University Medicine Berlin
University of Cambridge
The Francis Crick Institute
Michael Mülleder
Charité University Medicine Berlin
The Francis Crick Institute
University of Cambridge
Balázs Papp
Hungarian Academy of Sciences
Mohammad Tauqeer Alam
United Arab Emirates University
M. Ralser
The Francis Crick Institute
Charité University Medicine Berlin
University of Oxford
University of Cambridge
Cell
0092-8674 (ISSN) 1097-4172 (eISSN)
Vol. 186 1 63-79.e21Subject Categories
Cell Biology
Immunology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
DOI
10.1016/j.cell.2022.12.007
PubMed
36608659