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Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
Cell. 2023 Jan 5;186(1):63-79.e21. doi: 10.1016/j.cell.2022.12.007.
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
Abstract:
...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.
PMID: 36608659
Free Full-Text: https://www.cell.com/cell/fulltext/S0092-8674(22)01520-3