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

Correia-Melo, Clara and Kamrad, Stephan and Tengölics, Roland and Messner, Christoph B. and Trebulle, Pauline and Townsend, StJohn and Varma, Sreejith Jayasree and Freiwald, Anja and Heineike, Benjamin M. and Campbell, Kate and Herrera-Dominguez, Lucía and Aulakh, Simran Kaur and Szyrwiel, Lukasz and Yu, Jason S.L. and Zelezniak, Aleksej and Demichev, Vadim and Mülleder, Michael and Papp, Balázs and Alam, Mohammad Tauqeer and Ralser, Markus (2023) Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan. CELL, 186 (1). 63-79.e21. ISSN 0092-8674

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Abstract

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. © 2022 The Author(s)

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