Some kinds of aging damage are easy to imagine reversing. Cells can be cleared, senescent cells can be killed, worn tissue can regenerate. But a quieter, more stubborn kind of damage has long looked permanent: the slow chemical caramelization of our own proteins. Sugars react with long-lived proteins to form advanced glycation end-products (AGEs), which accumulate for decades in tissues that rarely renew — artery walls, skin, the lens of the eye. The body has no efficient way to remove them, and they stiffen tissue and drive age-related dysfunction. Clearing them has been, in the words of longevity investor Karl Pfleger, “a problem long considered unsolvable in the aging field.”

A new paper suggests that problem may be more solvable than assumed. In Nature Communications (2026), “Reversal of protein chemical aging by enzymatic deglycation,” a team led by Revel Pharmaceuticals — with collaborators at Calico and the University of Colorado — reports an engineered enzyme that removes a major AGE from naturally aged human tissue.

What they built

The enzyme, nicknamed CMLase (variant CrGO-897), is an engineered glycine oxidase derived from the thermophilic bacterium Calidithermus roseus. It targets Nε-carboxymethyl-lysine (CML), described as the most abundant AGE that forms on the amino acid lysine. Rather than trying to block AGEs from forming, CMLase works like a molecular lawnmower: it oxidizes and trims the carboxymethyl group back off the protein, reversing a modification previously treated as one-way.

What happened in human tissue

The results that got the field’s attention came from real, naturally aged human tissue tested outside the body:

Revel CEO Aaron Cravens summarized the effect bluntly: they were “reducing the levels back to that of what we’d see in like a 30-year-old.” In other words, an enzyme took a hallmark of chemical aging in 75-year-old tissue and rolled it back toward youthful baselines.

Why this is a “repair” approach. Most anti-aging strategies slow a process down — less inflammation, better metabolism, fewer senescent cells. CMLase does something different: it removes damage that has already accumulated. That puts it in the same conceptual bucket as senolytics and crosslink-breakers — therapies that aim to subtract existing damage rather than merely decelerate its buildup.

The honest caveats

This is an important proof of concept, not a therapy you can get. A few things to keep in mind:

Still, the significance is real: a class of damage the body cannot undo, and that researchers long treated as permanent, was enzymatically reversed in human tissue. That is exactly the kind of result that turns “irreversible” into “not yet reversed.”