Think of your body as an oven running at a low, constant temperature for decades. The same chemical reactions that give bread its golden crust — sugars reacting with proteins under heat — happen slowly inside us too. The sticky molecular residue they leave behind is called advanced glycation end products, or AGEs. And for forty years, scientists assumed that once they formed, they were there to stay.
A team at Revel Pharmaceuticals in San Francisco has just proved that assumption wrong.
The Body’s Rust
AGEs are sometimes called the body’s rust — and the analogy is apt. They coat structural proteins, gradually stiffening and damaging them. Unlike the cells themselves, which the body replaces relatively quickly, the structural scaffolding surrounding them is extraordinarily long-lived. It takes around fifteen years for the body to replace just half of its collagen.
That staying power comes at a cost: the longer these proteins persist, the more AGE damage accumulates.
The consequences extend well beyond wrinkles and creaky joints. AGEs stiffen blood vessels, inflame tissues, damage the brain’s immune cells, and increase the risk of heart disease, diabetes, kidney failure, and vision loss. They’re one of the most pervasive and underappreciated hallmarks of biological ageing — and they affect roughly 70% of the body’s mass, which is made up of structural proteins rather than cells.
Previous attempts to clear AGEs have largely failed. Some drugs can stop new ones forming, but nothing has successfully removed those already embedded in tissue. That failure led many scientists to conclude the damage was simply irreversible.
Looking to Microbes for a Solution
The Revel team approached the problem from an unusual angle. Human remains — including AGE-laden proteins — are eventually broken down by microbes in the soil. Those microbes, the researchers reasoned, might have evolved enzymes capable of dismantling the very molecular structures that stump the human body’s own repair systems.
The team screened DNA sequences from over 50,000 microbial species using AI, predicting the structures of the enzymes they encoded and narrowing the search to candidates capable of reaching AGEs buried deep within structural proteins like collagen. The winning candidate came from a bacterium that thrives in geothermal hot springs.
The enzyme showed promise — but barely enough to be useful. So the team applied directed evolution, a Nobel Prize-winning technique that mimics natural selection in accelerated form. After five rounds of evolution and more than 500 million variants tested, they produced CMLase: an engineered enzyme more than ten times more effective than its bacterial ancestor at dismantling CML, the most abundant and damaging form of AGE in human tissue.
Making 75-Year-Old Tissue Look 30
The most striking test came when CMLase was applied to donated human tissue. In slices of aortic tissue — the body’s largest blood vessel — from a 75-year-old donor, the enzyme reduced CML levels by roughly 70%, bringing them down to concentrations typically seen in a 30-year-old. Skin and eye lens proteins from a 64-year-old donor showed similarly significant reductions.
“We were pretty floored,” said Aaron Cravens, Revel’s CEO.
It’s an important result to calibrate carefully. Chemical reversal is not the same as tissue rejuvenation — it’s not yet known whether stripping away AGEs actually restores the function of stiffened tissues, or simply removes the chemical modification without repairing the underlying damage. Those questions require further study.
But the finding does overturn a foundational assumption that has shaped ageing research for four decades. And it points to a largely overlooked target: the structural scaffold surrounding cells, rather than the cells themselves, which has been the almost exclusive focus of longevity research until now.
What Could Come Next
The potential applications are wide. CMLase could in theory be formulated as eye drops to clear AGEs from the lens, applied to restore elasticity in stiffened blood vessels, or used to treat skin. It could be particularly valuable for people with type 2 diabetes, who accumulate these compounds at an accelerated rate.
Obstacles remain. Because CMLase evolved from a bacterial protein, the immune system may treat it as foreign and mount a response, especially with repeated doses. The body’s own enzymes may break it down before it reaches its targets. And it will need to penetrate the dense biological sheath surrounding organs to do its work. The team is actively working on improving its stability, safety, and delivery.
But perhaps the most significant implication is the one beyond CMLase itself. CML is just one member of the AGE family. If an engineered enzyme can reverse this type of molecular damage, the same approach might be applied to others — gradually chipping away at the accumulated chemical scars of ageing, one target at a time.
The body’s rust, it turns out, may not be as permanent as we thought.