TY - JOUR
T1 - Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
AU - Correia-Melo, Clara
AU - Kamrad, Stephan
AU - Tengölics, Roland
AU - Messner, Christoph B.
AU - Trebulle, Pauline
AU - Townsend, St John
AU - Jayasree Varma, Sreejith
AU - Freiwald, Anja
AU - Heineike, Benjamin M.
AU - Campbell, Kate
AU - Herrera-Dominguez, Lucía
AU - Kaur Aulakh, Simran
AU - Szyrwiel, Lukasz
AU - Yu, Jason S.L.
AU - Zelezniak, Aleksej
AU - Demichev, Vadim
AU - Mülleder, Michael
AU - Papp, Balázs
AU - Alam, Mohammad Tauqeer
AU - Ralser, Markus
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2023/1/5
Y1 - 2023/1/5
N2 - 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.
AB - 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.
KW - chronological aging
KW - eukaryotic longevity
KW - metabolic microenvironment
KW - metabolite exchange interactions
UR - http://www.scopus.com/inward/record.url?scp=85145415828&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85145415828&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2022.12.007
DO - 10.1016/j.cell.2022.12.007
M3 - Article
C2 - 36608659
AN - SCOPUS:85145415828
SN - 0092-8674
VL - 186
SP - 63-79.e21
JO - Cell
JF - Cell
IS - 1
ER -