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.


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.

Keywords: chronological aging; eukaryotic longevity; metabolic microenvironment; metabolite exchange interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Longevity*
  • Methionine / metabolism
  • Saccharomyces cerevisiae* / metabolism
  • Signal Transduction


  • Methionine