A polyamine compound found in ribosomes and living tissues present in all human cells is thought to be linked to aging and disease. Spermidine was discovered in sperm by Antonie van Leeuwenhoek, a Dutch microscopist known for his work in microbiology and microscopy more than 300 years ago. Years later, this molecule is better understood: scientists have proven that it is in fact present in all our cells and regulates various biological phenomena. A new study by scientists at the Boyce Thompson Institute and Cornell University has shown that, in combination with sirtuins, and other molecules it is involved in aging. This could become a tool in the fight against disease. The results of this work were published in the journal Nature.
Sirtuin Enzymatic Activities Credit: Irma R. Fernandez
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Aging and disease: New molecules involved in these processes
Recent studies indicate that sirtuins play a crucial role in various age-related diseases. Scientists are therefore trying to understand the link between sirtuins and aging, in the hope of developing new therapeutic options to improve health and life expectancy. In this work, the researchers used a method called comparative metabolomics to track sirtuin-dependent metabolic changes. This allowed them to identify acylspermidines, metabolites derived from changes in various proteins, many of which play a key role in cell growth and survival and are linked to sirtuins. In various molecular and mammalian assays, they found that these metabolites have an impact on cell lifespan and proliferation. “We were very excited to discover this unexpected branch of cell metabolism linked to sirtuins,” comments one of the authors, Frank Schroeder. In his opinion, this discovery paves the way for a better understanding of these biological processes and the role of mitochondrial sirtuins.
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The treatments of the future
Important physiological functions are reflected in countless molecular fingerprints, including tens of thousands of metabolites, small molecules that have not yet been discovered,” explains Bingsen Zhang, lead author of the study. This work is a step towards discovering biological roles and functions in our bodies.” The researchers plan to continue their work to define possible pharmacological applications. In particular, they are examining “how acylated spermidines affect lifespan, cell growth, and their possible interactions with other metabolic pathways.”
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References
Zhang, B., Mullmann, J., Ludewig, A.H. et al. Acylspermidines are conserved mitochondrial sirtuin-dependent metabolites. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-023-01511-2
