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Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
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 12, Michael Mülleder 13, Balázs Papp 3, Mohammad Tauqeer Alam 14, Markus Ralser 15
...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.