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.
chronological aging
eukaryotic longevity
metabolite exchange interactions
metabolic microenvironment
Author
Clara Correia-Melo
The Francis Crick Institute
University of Cambridge
Charité University Medicine Berlin
Stephan Kamrad
The Francis Crick Institute
Roland Tengölics
Hungarian Academy of Sciences
Christoph B. Messner
The Francis Crick Institute
University of Zürich
Pauline Trebulle
University of Oxford
The Francis Crick Institute
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
Medical Research Council
Imperial College London
The Francis Crick Institute
University of Oxford
Kate Campbell
University of Cambridge
Lucia Herrera-Dominguez
The Francis Crick Institute
Simran Kaur Aulakh
The Francis Crick Institute
University of Oxford
Lukasz Szyrwiel
The Francis Crick Institute
Charité University Medicine Berlin
Jason S.L. Yu
The Francis Crick Institute
Aleksej Zelezniak
Chalmers, Life Sciences, Systems and Synthetic Biology
The Francis Crick Institute
Vilnius University
Vadim Demichev
Charité University Medicine Berlin
The Francis Crick Institute
University of Cambridge
Michael Mülleder
University of Cambridge
Charité University Medicine Berlin
The Francis Crick Institute
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 Cambridge
University of Oxford
Cell
0092-8674 (ISSN) 1097-4172 (eISSN)
Vol. 186 1 63-79.e21Subject Categories (SSIF 2011)
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