summary: Researchers reveal a link between acylspermidines, a family of metabolites, and sirtuins, enzymes important in aging and disease. Recent studies suggest a role for sirtuins in age-related diseases, making them promising therapeutic targets for longevity and health span.
The discovery of sirtuin-binding acylspermidines in C. elegans and mammals opens new horizons for understanding and potentially manipulating these pathways. This advance in biochemistry brings us closer to uncovering the roles of acylspermidines in cell lifespan and proliferation.
- Acylspermidines, newly discovered metabolites, reveal an unexpected relationship between sirtuins and cellular metabolism.
- Sirtuins are enzymes implicated in age-related diseases and are potential targets for extending healthy lifespan and longevity.
- This study highlights the importance of revealing hidden biochemical pathways in understanding aging and disease processes.
source: Boyce Thompson Institute
In a major advance in the field of biochemistry, scientists at the Boyce Thompson Institute (BTI) and Cornell University have revealed new insights into a family of metabolites, acylspermidines, that could change how we understand aging and fight disease.
The study was recently published in Nature and chemical biologypresents an unexpected connection between spermidine, a long-known compound found in all living cells, and sirtuins, an enzyme family that regulates many of life's essential functions.
Sirtuins have been the subject of great interest over the past two decades. Recent studies suggest that sirtuins play a crucial role in many age-related diseases. As a result, there is increasing interest in the link between sirtuins and aging, making them a promising target for therapeutic interventions aimed at improving health and longevity.
“We were excited to uncover this unexpected branch of cellular metabolism associated with sirtuins,” said lead author Frank Schroeder, a professor at BTI. “The discovery of previously uncharacterized spermidine derivatives provides insight into the inner workings of this critical pathway and brings us one step closer to understanding the physiological functions of mitochondrial sirtuins.”
The researchers took an unbiased approach, comparative metabolomics, a methodology that Schroeder's lab has been developing for more than a decade, to examine sirtuin-dependent metabolic changes. The study revealed a new family of metabolites called acylspermidines, which are derived from modifications of diverse proteins, many of which play essential roles in growth and cell survival.
After the discovery of sirtuin-binding acylspermidines in simple organisms C. elegansThe researchers also demonstrated that the same compounds are also found in mammals (including humans). Finally, the research team demonstrates the direct effect of these metabolites on lifespan C. elegans and cell proliferation in mammals.
“Important physiological functions are reflected in many molecular signatures, including tens of thousands of small-molecule metabolites that have not yet been discovered,” says Bingsen Zhang, a graduate student in Schroeder’s lab and first author of the study. “This work is a step toward uncovering the roles of “And the biological functions of the vast expanse of dark chemicals in our bodies.”
Future research will explore the mechanisms and pharmacological aspects of these findings, in particular how acylspermidine affects lifespan and cell growth and its potential interactions with other metabolic pathways.
“Nearly 350 years after the isolation of spermidine and 100 years of understanding its structure, our work advances the collective knowledge of the spermidine family, linking it to other vital biochemical processes, including central energy metabolism and amino acid metabolism,” Zhang added.
This is a collaborative study with researchers from the Weiss Laboratory at Cornell University College of Veterinary Medicine.
Financing: This work was supported in part by the National Institutes of Health and HHMI.
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author: Mike Carroll
source: Boyce Thompson Institute
communication: Mike Carroll – Boyce Thompson Institute
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“Acylspermidines are sirtuin-dependent mitochondrial metabolites“By Frank Schroeder et al. Nature and chemical biology
Acylspermidines are sirtuin-dependent mitochondrial metabolites
Sirtuins are nicotinamide adenine dinucleotide (NAD).+) – a protein-dependent lysine deacetylase that regulates metabolism and stress responses; However, characterization of the removed acyl groups and their ultimate metabolic fates remains incomplete.
Here we used untargeted comparative metabolomics to re-examine the biochemistry of mitochondrial sirtuins.
First, we defined n-Glutarylspermidine as metabolites downstream of mitochondrial sirtuin SIR-2.3 in Certain types are elegant It was demonstrated that SIR-2.3 functions as a lysine deglutarylase nGlutarylspermidine can be extracted from… Hey-Glutaryl-ADP-ribose.
Subsequent targeted analysis of C. elegansHuman and rat metabolomics revealed a chemically diverse array of… n– Acylspermidine, and its composition n-Succinylpyrimidine and/or nGlutarylspermidine was observed downstream of the mammalian sirtuin SIRT5 in two cell lines, consistent with annotated functions of SIRT5.
finally, n– Glutarylspermidine was found to have a negative effect C. elegans Lifespan and proliferation of mammalian cells.
Our results suggest so n-Acyl pyrimidines are conserved metabolites downstream of mitochondrial sirtuins that facilitate annotation of sirtuin enzymatic activities in vivo and may contribute to sirtuin-dependent phenotypes.