A team of researchers has developed an engineered enzyme capable of breaking down advanced glycation end products (AGEs), compounds associated with aging and tissue damage, according to a study published recently in Nature Communications. AGEs form over decades as sugars react with proteins and fats in the body, contributing to tissue stiffening, inflammation, and conditions such as heart disease, kidney damage, eye impairment, and diabetes.
Efforts to create drugs that prevent AGE formation have largely been unsuccessful. Instead, researchers led by Aaron Cravens, chief executive of Revel Pharmaceuticals and the study’s lead author, pursued a novel approach aimed at removing AGEs after they have accumulated in human tissues. By enzymatically clearing these compounds, the team sought to restore tissue function and potentially reverse some markers of aging.
“Aging is very complicated,” Cravens commented, describing the study as a modest but significant advance in addressing the biochemical aspects of aging. Unlike previous interventions focusing primarily on cellular repair and regeneration, this research targeted extracellular matrix components such as collagen, which become stiff and sticky due to AGE accumulation.
AGEs have long been known to act like “rust” on tissue proteins, explained John Baynes, a retired biochemist who specialized in AGE research but was not involved in the study. While the harmful effects of these compounds have been studied extensively, attempts to halt their formation with pharmaceutical agents have not yielded viable treatments.
The team began with the premise that since dead human tissue naturally returns to the biosphere, there must be biological mechanisms capable of degrading even the durable AGE molecules. They turned to microbial enzymes, leveraging artificial intelligence to analyze DNA sequences from approximately 50,000 microbes and predict the three-dimensional structures of their enzymes. This computational screening narrowed the candidates to several enzymes potentially able to cleave AGEs from human proteins.
After identifying a promising enzyme, researchers engineered it for enhanced efficiency and named it CMLase. Laboratory tests showed that CMLase could substantially reduce AGE levels in human tissue samples. In one notable experiment, 70-year-old human skin tissue treated with the enzyme exhibited AGE concentrations comparable to those found in 30-year-old skin.
While these findings open new avenues for AGE-targeted therapies, further research will be necessary to assess the enzyme’s safety, efficacy, and practical application in clinical settings. Nonetheless, the study offers a promising step toward interventions that could mitigate some aging-related tissue damage by addressing a previously intractable biochemical process.