Regulation of Folate Metabolism Pathways Found to Increase Lifespan
The regulation of folate metabolism has been found to underlie many known signaling pathways related to aging.
Starting with the roundworm, they observed clear changes in the metabolites and enzymes of the folate cycle in all worm lines.
Reducing the activity of specific enzymes of folate metabolism in the worms resulted in an increase in lifespan of up to 30 percent.
Several different causes of ageing have been discovered, but the question remains whether there are common underlying mechanisms that determine ageing and lifespan. Researchers from the Max Planck Institute for Biology of Ageing and the CECAD Cluster of Excellence in Ageing research at the University Cologne have now come across folate metabolism in their search for such basic mechanisms. Its regulation underlies many known ageing signalling pathways and leads to longevity. This may provide a new possibility to broadly improve human health during ageing.
In recent decades, several cellular signalling pathways have been discovered that regulate the lifespan of an organism and are thus of enormous importance for ageing research. When researchers altered these signalling pathways, this extended the lifespan of diverse organisms. However, the question arises whether these different signalling pathways converge on common metabolic pathways that are causal for longevity.
The search begins in the roundworm
The scientists started their search in the roundworm Caenorhabditis elegans, a well-known model organism for ageing research. "We studied the metabolic products of several, long-lived worm lines. Our analyses revealed that, among other things, we observed clear changes in the metabolites and enzymes of the folate cycle in all worm lines. Since folate metabolism plays a major role in human health, we wanted to further pursue its role in longevity", explains Andrea Annibal, lead author of the study.
A common mechanism for longevity
Folates are essential vitamins important for the synthesis of amino acids and nucleotides - the building blocks of our proteins and DNA. "We tuned down the activity of specific enzymes of folate metabolism in the worms. Excitingly, the result was an increase in lifespan of up to 30 percent", says Annibal. "We also saw that in long-lived strains of mice, folate metabolism is similarly tuned down. Thus, the regulation of folate metabolism may underlie not only the various longevity signalling pathways in worms, but also in mammals."
"We are very excited by these findings because they reveal the regulation of folate metabolism as a common shared mechanism that affects several different pathways of longevity and is conserved in evolution", adds Adam Antebi, director at the Max Planck Institute for Biology of Ageing. "Thus, the precise manipulation of folate metabolism may provide a new possibility to broadly improve human health during ageing." In future experiments, the group aims to find out the mechanism by which the folate metabolism affects longevity.
This study was published in Nature Communications in June 2021.