Berlin, 6 December 2023
If cells exchange metabolic products with each other, they live longer. A research team at Charité – Universitätsmedizin Berlin has now been able to show this for the first time in a study using yeast cells as an example. The fact that the exchange of substances has a direct influence on the lifespan of cells could play an important role in future research into aging processes and age-related diseases in humans. The study has been published in the current scientific journal Cell*.
Metabolism and aging are inseparable: Metabolic processes contribute to the maintenance of vital functions, ensure growth or trigger repair measures in cells. But substances are also produced that are harmful to the cell and drive the aging process. “The metabolic processes that take place inside cells are highly complex,” says Prof. Dr. Markus Ralser, director of the Institute of Biochemistry at Charité and Einstein Professor of Biochemistry. “Among other things, the exchange of substances between cells of a cell community plays a central role, because it significantly influences the internal cell metabolism.” Cells are in constant exchange with neighboring cells – for example, in body tissues: they excrete unneeded substances from their cell interior and take up substances from their environment. In a recent study, the team led by metabolism expert Prof. Ralser investigated whether the exchange of metabolites has an influence on the lifespan of cells.
For their studies, the researchers worked with yeast cells and conducted experiments to determine lifespan. Yeast cells are an important model for basic research, a dominant microorganism in biotechnology and also important in medicine because they can cause fungal infections. “We were able to show that the lifespan of the cells increased by about 25 percent when they were able to exchange metabolites with each other,” says Dr. Clara Correia-Melo, also from the Institute of Biochemistry at Charité and first author of the study. “Now, of course, we wanted to know which substances and exchange processes were behind this life-prolonging effect.” To find out, the researchers used a special examination system supported by mass spectrometry, which allows them to precisely track the exchange of substances between cells. They found that young cells that were still dividing well and often excreted amino acids, and that these were taken up by the older cells.
Amino acids are the building blocks that make up proteins. The research team found that the exchange of the amino acid methionine prolongs the life of the cells involved. The amino acid is found in all organisms and plays an important role in protein production and also in many cellular processes. “The interesting thing is that the metabolism of the young cells was responsible for prolonging the life of the old cells,” says Prof. Ralser. Some young cells released methionine, which other young cells took up. This changed their cell metabolism in such a way that they excreted metabolic products from which the methionine-producing cells benefited. These products include glycerol, which is needed to build cell membranes and has cell-protective properties. “If long-lived methionine-absorbing cells give off glycerol, they thereby also prolong the life of the methionine-producing cells – a win-win situation,” explains Dr. Correia-Melo. “And this cooperative exchange of substances between cells extends the life of the entire cell community.”
With their study, the researchers were able to show for the first time, using yeast cell communities, that mass transfer has a direct influence on the lifespan and aging process of cells. They suspect that this also applies to other cell types, such as human somatic cells, and intend to test this in further studies. “In order to investigate the development of age-related diseases such as diabetes, cancer or neurodegenerative diseases, we need to better understand the complex metabolic pathways within, but also between, cells,” says Prof. Ralser. “The exchange of substances between cells is a hitherto overlooked but clearly decisive factor in the cellular aging process. We hope that with our study we can contribute to an increased focus on the exchange of metabolites between cells in the future.” In subsequent research projects, Prof. Ralser would like to investigate the exact mechanisms of the cell-protecting and life-prolonging effect of glycerol in more detail.
About the study
Prof. Ralser and Dr. Correia-Melo started the initial investigations for the present study six years ago at the University of Cambridge, continued them at the Francis Crick Institute in London and finished them at the Institute of Biochemistry at the Charité – Universitätsmedizin Berlin. The work was carried out in close cooperation with the Hungarian Academy of Sciences. The research project was funded by the Wellcome Trust, an ERC Synergy Grant from the European Commission, the EU-CoBioTech project Sycolim and within the funding line Research Cores for Mass Spectrometry in Systems Medicine (MSCoreSys) of the German Federal Ministry of Education and Research (BMBF).
Photo Credit: Self-Establishing Communities (SeMeCos) © Kate Campbell, Markus Ralser l CC-BY, https://doi.org/10.7554/eLife.09943.002 (0,95 MB)
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