Intercellular metabolite exchange may extend each other's lifespan

Researchers from the Charité School of Medicine in Berlin, Germany, the Francis Crick Institute in the United Kingdom, and the University of Cambridge employed yeast cells as subjects in a new study and discovered that cells survive longer when they exchange metabolites with other cells. These exchanges have a direct effect on cell longevity, which might be useful in future studies of the human aging process and age-related disorders.

The findings were published in the January 5, 2023 issue of Cell, titled "Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan".

Aging and metabolism are intricately related. While it aids in the maintenance of critical processes that allow us to develop and repair our cells, it also creates molecules that destroy our cells and cause us to age. Professor Markus Ralser, co-corresponding author and head of the Department of Biochemistry at Berlin's Charité School of Medicine, commented, "The metabolic processes that take place within cells are extremely complicated. The exchange of substances between cells in a cell population is significant because it has a large impact on the metabolism that occurs within the cell."

Within tissues, for example, cells are constantly interacting with neighboring cells. They expel certain pollutants while absorbing others from their surroundings. A recent study conducted by Professor Ralser explored whether the interchange of metabolites impacts cell lifespan.

These authors used yeast cells and performed experiments to determine their longevity. Yeast cells are a key model in basic research, a major microorganism in biotechnology and important in medicine because they can cause fungal infections. "We found that when these cells exchanged more metabolites with each other, their lifespan was extended by about 25 percent," said the first author of the paper, Dr. Clara Correia-Melo of the Department of Biochemistry at the Charité School of Medicine in Berlin. "Therefore, we obviously wanted to identify the substances and exchange processes behind this life-extending effect."

These researchers used a sophisticated analytical method accompanied by a mass spectrometer to accurately measure the exchange of metabolites between cells. They discovered that amino acids produced by young yeast cells that continue to proliferate rapidly are commonly taken up by older yeast cells.

Amino acids are the building blocks of proteins. These researchers discovered that exchanging an amino acid called methionine increased the longevity of yeast cells engaged in the exchange. Methionine is found in all species and is essential for protein synthesis as well as a variety of other cellular activities. "Interestingly, it is the metabolism of young cells that extends the life span of older cells," explained professor Ralser.

This research of yeast cell communities demonstrates for the first time that metabolite exchange has a direct impact on cell longevity and the aging process. The authors assumed that this also applies to other types of cells, such as those found in the human body, and planned to investigate this further.

When it comes to cell analytical studies, single cell analysis must be mentioned as individual cells in populations differ dramatically in size, protein levels, and expressed RNA transcripts, and it applies to analyze genomics, transcriptomics, proteomics, and metabolomics at the single-cell level, enabling it possible to discover mechanisms not seen when studying a bulk population of cells. Representative operations include single cell sequencing analysis and functional analysis

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