Alive, elastic, youthful — held together by collagen fibres beneath each cell.
These protein fibres support every skin cell. They last for decades — accumulating chemical damage the whole time.
Collagen runs in long helical strands. Each strand is a chain of amino acids — including lysine.
The amino acid that collagen is built from. Thousands of them, end to end.
Glucose is always circulating. It reacts with lysine in a process called glycation.
Nε-carboxymethyllysine — a permanent chemical scar. Your body has no way to remove it. It builds up for decades.
Scars build up across your collagen — stiffening and cross-linking the fibres. The protein loses its function.
Skin loses its support structure. Cells sag. The scaffold your tissue relies on becomes rigid and scarred.
An engineered enzyme — the first proven to reverse this damage. Revel Pharmaceuticals screened over 500 million variants to find it. Published in Nature Communications, July 2026.
CMLase removes the chemical scars. In donated human tissue aged 20–75, CML was reduced by >55% in skin and >70% in arteries — to levels of tissue decades younger.
This work was performed ex vivo. Clinical trials are several years away.
CML up to July 2026 on Twitter
Dr. Ahmed identifies Nε-carboxymethyllysine (CML) while investigating products formed in glucose-lysine reactions under physiological conditions. It becomes the first glycoxidation product ever characterised, launching an entirely new field of study.
CML is established as the most abundant Advanced Glycation End Product in tissue proteins and the gold-standard biomarker of glycoxidative, lipoxidative, and carbonyl stress. Research communities form in food science, diabetes, and gerontology.
The Receptor for Advanced Glycation End Products (RAGE) is fully characterised as an immunoglobulin-family transmembrane receptor. Researchers establish the CML–RAGE signalling axis as a key driver of chronic inflammation in aging, diabetes, and cardiovascular disease.
Advances in high-throughput screening, computational protein design, and directed evolution (Francis Arnold's Nobel-Prize-winning field) make it feasible to screen hundreds of millions of enzyme variants. The tools that would eventually create CMLase come of age.
Revel Pharmaceuticals is founded with the explicit mission of reversing protein glycation damage. A collaboration forms between Revel, Google/Alphabet's longevity subsidiary Calico Life Sciences, and the University of Colorado Anschutz Medical Campus, bringing together biotech, industry, and academic rigour.
Starting from glycine oxidase in the thermophilic hot-spring bacterium Calidithermus roseus (chosen for chemical similarity between glycine and the CML moiety), the team screens over 500 million enzyme variants. CrGO-897, harbouring three mutations (E80Q, H226A, H230R), emerges as CMLase.
The paper "Reversal of protein chemical aging by enzymatic deglycation" is published. CMLase reduces CML in aged skin tissue by >55%, in 75-year-old arterial tissue by >70%, and in lens proteins by 45–78%. For the first time, protein glycation is shown to be enzymatically reversible in human tissue.
Read the paper →Nature Communications · July 14, 2026
"Reversal of protein chemical aging by enzymatic deglycation" — Aaron Cravens et al.
Revel Pharmaceuticals, Calico Life Sciences & University of Colorado Anschutz.
CMLase has reversed protein damage in donated human tissue. Getting from bench to bedside requires answering critical questions first.
Projected path: IND application → Phase 1 safety → Phase 2 efficacy (est. 2028–2029 if development proceeds)
Stay Informed →CMLase is pre-clinical — no human trials yet. But the science of reducing CML accumulation is well established.