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

Clara Correia-Melo1 2, Stephan Kamrad3, Christoph B. Messner4, Roland Tengölics5, Lucía Herrera- Dominguez6, St John Townsend6, Mohammad Tauqeer Alam7, Anja Freiwald1, Kate Campbell8, Aleksej Zelezniak9, Vadim Demichev1, Michael Muelleder1, Balázs Papp5, Markus Ralser6 10

1Charité - Universitätsmedizin Berlin, Berlin, Germany,
2Francis Crick Institute, United Kingdom,
3The Francis Crick Institute, Biomedical Research Centre, 1 Midland Road, London, United Kingdom,
4Francis Crick Institute, Biomedical Research Centre, 1 Midland Road, London, United Kingdom,
5Szegedi Biológiai Kutatóközpont Magyar Tudományos Akadémia, Szeged, Hungary,
6The Francis Crick Institute, Biomedical Research Centre, 1 Midland Road, London,,
7United Arab Emirates University, Al Ain, United Arab Emirates,
8Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom,
9Chalmers University of Technology, Gothernburg, Sweden,
10Charité - Universitätsmedizin Berlin, Biomedical Research Centre, 1 Midland Road, Berlin, Germany

Metabolism is deeply intertwined with ageing. Effects of metabolic interventions on ageing have, thus far, been explained with intracellular metabolism, growth control and signalling. Studying chronological ageing in yeast, we reveal a so far overlooked metabolic property that influences ageing via the cooperative exchange of metabolites. We observed that metabolites exported by young cells are re-imported by chronologically ageing cells, resulting in cross-generational metabolic interactions. Then, we used synthetic cell communities as a tool to boost cell-cell metabolic interactions, and achieve significant lifespan extensions. Combining proteomics, metabolomics and modelling, we reveal a specific role of long-lived methionine consumer cells. These were enriched with ageing, but also increased the export of protective metabolites that, in turn, extended the lifespan of cells that supplied them with methionine. Our results establish cooperative metabolite exchange interactions as a determinant of cellular ageing, and show that microbial communities shape their metabolic environment to extend lifespan.

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