Researchers engineered an enzyme capable of removing N-carboxymethyl-lysine (CML), a prevalent advanced glycation end product, from proteins both in isolation and embedded within peptide chains. This represents the first demonstration that age-related protein glycation—previously considered irreversible—can be enzymatically reversed, with potential implications for addressing tissue stiffness and chronic inflammation associated with aging.
Key Points
- Engineered enzyme (CMLase) removes glycation damage from proteins efficiently
- Protein crosslinking and inflammation from AGEs may become therapeutically reversible
- Directed evolution accelerated enzyme optimization across five iterative selection rounds
Longevity Analysis
The accumulation of glycated proteins in long-lived tissues like collagen represents a significant mechanism of aging—one that has resisted therapeutic intervention. By demonstrating enzymatic reversal of this modification, this work opens a pathway to address structural and inflammatory consequences of protein damage that persist for decades in the extracellular matrix. The approach does not eliminate glycation at its source but targets the damage after it forms, suggesting a complementary strategy to dietary and metabolic interventions that slow AGE formation. Translation to clinical efficacy will depend on enzyme delivery to tissue compartments where glycated proteins accumulate and on sustained reduction of inflammatory signaling from damaged protein-receptor interactions.
Original published by LifeSpan.io, by Arkadi Mazin.