Yeast Cells Reconfigure Their Metabolomes to Live Longer

A complex orchestration of metabolic processes creates energy and influences cell survival. But metabolism is not a cloistered, intracellular process. In a study published in Cell, scientists showed how yeast cells that shared a specific metabolite reshaped their communal metabolic environment and lived longer.¹  

Yeast are single-celled organisms, but their lives are far from solitary. “Microbes love communities,” said Markus Ralser, a biologist at the Francis Crick Institute and senior author of the study. One benefit of communal living is collaborating on energy-intensive activities. Some cells export metabolites into their surroundings, which nearby cells import to fulfill their own metabolic needs. 

Curious about how this exchange influences aging, Ralser turned his sights to aging yeast communities. Studying metabolite exchange within microbial communities is challenging, as single-cell techniques overlook the extracellular space. To overcome this limitation, the team generated self-establishing metabolically cooperating communities (SeMeCos) of yeast that are designed to only produce or consume key amino acids.² 

         

Rasler was surprised to find that SeMeCos lived significantly longer than wild-type yeast communities. A closer look into the extracellular metabolites—exometabolome—revealed that cells lived longer if they produced the amino acid methionine or neighbored methionine-producers. 

These findings intrigued Ralser and his team. Upon further investigation into the metabolome, they found that methionine-consuming cells reconfigured their metabolism to export protective metabolites, such as glycerol, which extends yeast lifespans, back into the metabolome.³ Ralser’s team then looked at cross-generational cells and linked these beneficial methionine exchange interactions in the exometabolome to elevated concentrations of anti-aging metabolites in older cells. 

Kiran Patil, a biologist at Cambridge University who was not involved in the study, noted that the findings support a new way of looking at fundamental biological processes like aging. “We like to look inside the cell. At the same time, equally important is the environment, what's outside the cells, because that determines what the selection pressure is but also how the cell responds to it.”