BTI and scientists at Cornell University have discovered spermidine, a metabolite that could redefine our understanding of aging and disease**.
In a major advance in the field of biochemistry, scientists at the Boyce Thompson Institute (BTI) and Cornell University have discovered new insights into the metabolite spermidine family, which could change our understanding of aging and fighting disease.
The study, recently published in Nature Chemical Biology, proposes an unexpected link between spermidine, a well-known compound found in all living cells, and sirtuins, a family of enzymes that regulate many essential functions of life.
Sirtuins: The key to longevity and health.
Sirtuins have been the subject of much attention over the past two decades. Recent studies have shown that sirtuins play a vital role in a variety of age-related diseases. As a result, there is growing interest in the link between sirtuins and aging, making them a promising target for ** interventions aimed at improving healthy longevity and longevity.
We are pleased to discover this unexpected branch of cellular metabolism associated with sirtuins," said lead author, BTI professor Frank Schroeder. "The discovery of these previously uncharacterized spermidine derivatives could provide insight into the inner workings of this critical pathway and bring us closer to understanding the physiological function of mitochondrial sirtuins.
The researchers employed an unbiased approach, comparative metabolomics, a method that Schroeder's lab has been developing for more than a decade to screen for sirtuin-dependent metabolic changes. The study revealed a novel family of metabolites called acylspermidine, which are modified by a variety of proteins, many of which play a crucial role in growth and cell survival.
After the discovery of sirtuin-linked acylspermidine in the simple organism Caenorhabditis elegans, the researchers further demonstrated that the same compound is also present in mammals, including humans. Finally, the team demonstrated the direct effects of these metabolites on Caenorhabditis elegans longevity and mammalian cell proliferation.
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Important physiological functions are reflected in many molecular fingerprints, including tens of thousands of small molecule metabolites that remain to be discovered. This work is a step towards revealing the biological role and function of the vast space of chemical dark matter in our bodies," said Bingsen Zhang, a graduate student in the Schroeder lab and first author of the study.
Future studies will explore the mechanistic and pharmacological aspects of these findings, in particular how acylspermidine affects lifespan, cell growth, and their potential interactions with other metabolic pathways.
Nearly 350 years after spermidine was isolated and 100 years after its structure was understood, our work furthers the collective knowledge of the spermidine family, linking it to other important biochemical processes, including central energy metabolism and amino acid metabolism," Zhang added.
Reference: "Acylspermidine is a conserved mitochondrial sirtuin-dependent metabolites" by Bingsen Zhang, James Mullmann, Andreas H ludewig、irma r. fernandez、tyler r. bales、robert s.Weiss and Frank CSchroeder, January 2, 2024, Nature Chemical Biology.
doi： 10.1038/s41589-023-01511-2