Engineered Enzyme CMLase Cuts a Stubborn Aging Mark by up to 70% in Human Tissue

What happened

Researchers from Revel Pharmaceuticals, Calico, and the University of Colorado reported in Nature Communications (covered July 22, 2026) that they engineered an enzyme capable of reversing a major chemical mark of aging on proteins: Nε-carboxymethyl-lysine (CML).

CML is an advanced glycation end product (AGE) that accumulates on long-lived proteins in skin, blood vessels, and the eye. It stiffens tissue and can drive inflammation through the RAGE receptor. Until now, CML on intact proteins was widely treated as essentially irreversible.

How CMLase was built

Using directed evolution, the team screened more than 500 million enzyme variants across five engineering rounds, starting from a microbial enzyme scaffold. The resulting enzyme—CMLase—was tested on damaged lab proteins, human lens proteins, and preserved human skin and artery sections.

Key results reported:

• Up to 97% CML removal overnight on some lab-damaged proteins
• ~45% reduction in proteins from a 64-year-old human eye
• >70% reduction in elderly human artery sections
• ~55% reduction in human skin tissue

Caution and promise

This is proof-of-concept, not a clinic-ready therapy. As the study reporting notes, the enzyme still must be shown safe, deliverable into living tissue, and capable of meaningful functional improvement—not just biomarker reduction. Even so, CMLase reframes a stubborn aging chemistry problem as an engineering problem: if one AGE mark can be enzymatically erased, others may follow.

Key takeaways

• Directed evolution produced CMLase, which cleaves CML on intact proteins—a mark long treated as irreversible.
• Human tissue results include >70% reduction in elderly artery sections and ~55% in skin (ex vivo).
• Phys.org / Nature Communications coverage frames the work as early-stage: biomarker clearance is not yet a clinical therapy.