1. Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
- Author
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Clara Correia-Melo, Stephan Kamrad, Roland Tengölics, Christoph B. Messner, Pauline Trebulle, StJohn Townsend, Sreejith Jayasree Varma, Anja Freiwald, Benjamin M. Heineike, Kate Campbell, Lucía Herrera-Dominguez, Simran Kaur Aulakh, Lukasz Szyrwiel, Jason S.L. Yu, Aleksej Zelezniak, Vadim Demichev, Michael Mülleder, Balázs Papp, Mohammad Tauqeer Alam, and Markus Ralser
- Subjects
Chemical Biology & High Throughput ,Metabolism ,Ecology,Evolution & Ethology ,Synthetic Biology ,General Biochemistry, Genetics and Molecular Biology ,Computational & Systems Biology - 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.
- Published
- 2023
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