Engineered enzyme erases a stubborn mark of aging by up to 70% in human tissue samples

Key Points:

• Revel Pharmaceuticals, in collaboration with Calico and the University of Colorado, engineered an enzyme called CMLase that can reverse Nε-carboxymethyl-lysine (CML), a key protein damage linked to aging and inflammation, as detailed in their recent Nature Communications study.
• CML, part of harmful advanced glycation end products (AGEs), accumulates on long-lived proteins in tissues like skin, blood vessels, and eyes, contributing to tissue stiffening and chronic inflammation via the CML-RAGE signaling pathway.
• Using directed evolution, researchers screened over 500 million enzyme variants to develop CMLase, which reduced CML levels by up to 97% in lab tests and significantly lowered CML in human eye, skin, and artery tissues from elderly donors.
• While promising, CMLase is currently a proof-of-concept and requires further testing to confirm its safety, tissue penetration ability, and effectiveness in reducing inflammation or improving tissue function in living organisms.
• This breakthrough opens potential for developing regenerative therapies targeting various age-related protein modifications, potentially enabling repair of damaged tissues and advancing age-reversal treatments in the future.