The short answer

Glycation has not been reversed in living people. In July 2026, Trabosh and colleagues reported in Nature Communications that an engineered enzyme, CMLase, lowered one advanced glycation end product (AGE), carboxymethyl-lysine (CML), in laboratory-prepared human tissue, including thin fixed skin sections from a single 74-year-old donor. Dr. Dusan Sajic of Sajic Longevity reads it as a real chemistry breakthrough, not an anti-aging treatment: the useful plan today is to measure the right layer, prevent new damage, and remodel skin with treatments that have outcome evidence.

  • CMLase targets one AGE modification (CML). It has not been shown to remove glucosepane, the major collagen cross-link.
  • The skin result was more than 55% lower CML staining in fixed sections after 18 hours in a dish. No wrinkles, elasticity or biological age were measured.
  • There is no approved, commercial, compounded or clinic-delivered CMLase, and no human CMLase trials were found on ClinicalTrials.gov.
  • There is no validated "glycation age" test. HbA1c, CGM, skin autofluorescence, named-AGE assays and biopsy each answer a different question.
  • Today's plan is prevention plus remodeling: metabolic care, sun protection, no smoking, sleep and activity, and proven skin treatments, measured before and after.
>55%lower CML staining in fixed skin sections from one older donor, after 18 hours in the lab
1AGE modification targeted (CML). Glucosepane and other cross-links untouched in the evidence so far
>500Mcumulative enzyme library members reported in the engineering work
0human CMLase trials found on ClinicalTrials.gov (exact-term search, September 2026)

Did scientists just "uncook" aging?

No. The viral version of this story says an enzyme took a cooked meal back to its raw ingredients. That framing implies every AGE, every collagen cross-link and decades of tissue change were reversed. The study did not show that.

Glycation is the slow, non-enzymatic reaction between sugars and proteins. Over years it leaves chemical marks on long-lived proteins such as collagen, and some of those marks stiffen tissue or provoke inflammation. The kitchen analogy, browning a piece of toast, is a reasonable picture of how sugar and protein chemistry can form. It is a limited analogy for how it forms, not evidence that CMLase can uncook tissue.

What the study did show is still important. For years the safe assumption was that persistent AGE modifications could only be prevented, diluted slowly through tissue turnover, or worked around. CMLase is the first good evidence that at least one of them can be enzymatically removed from human protein.

What did the 2026 CMLase study actually test?

Trabosh and colleagues engineered an enzyme, CMLase (also called CrGO-897), to strip protein-bound CML, and tested it on laboratory material rather than living people. The paper, Reversal of protein chemical aging by enzymatic deglycation, was published in Nature Communications on July 14, 2026.

The skin result, read carefully

The skin experiment used thin (4.0 µm) fixed sections from one 74-year-old donor, treated with 5 µM enzyme for 18 hours and compared with an inactive version of the enzyme. CML immunostaining fell by more than 55%.

Do not overread it. The analysis covered four image regions, not four patients. The endpoint was a staining proxy, not wrinkles, elasticity, function or biological age. The tissue was fixed, not living, so the hard problems of delivery and penetration were never tested.

The other tissues

The paper reported results in other laboratory material too: about 45% in lens protein and more than 70% in fixed aorta sections. Again, these are preclinical and ex vivo endpoints. The engineering work behind the enzyme reported more than 500 million cumulative library members, which tells you how much protein design it took to find an enzyme that does this at all.

Did the enzyme make 74-year-old skin "younger" than 31-year-old skin?

No. The younger material came from a separate donor and was only a staining comparator. There was no matched before-and-after person, no biological-age measurement and no clinical outcome.

Disclosure

The paper reported NIH/NIA support and a Revel Pharmaceuticals provisional patent application listing two authors as inventors. Patent disclosure is relevant context. It does not by itself invalidate the experiment.

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One tag, not all of aging

Is CML the same as glucosepane, or "aging" itself?

No. CML is one AGE among many, glucosepane is a different and arguably more important one for skin, and aging is far larger than either.

TargetWhat it isHas CMLase been shown to remove it?
CML (carboxymethyl-lysine)A non-cross-linking, non-fluorescent AGE modification that accumulates in human tissue with diabetes and age. CMLase was engineered for protein-bound CML.Yes, in laboratory-prepared tissue only.
GlucosepaneA major protein cross-link of the aging human extracellular matrix, more abundant in diabetes. It is the kind of AGE that physically ties collagen fibres together.No.
"All aging"UV, inflammation, genetics, smoking, metabolic disease, senescence, matrix loss and many other mechanisms, not one chemical tag.No.

This distinction matters clinically. If you are hoping an enzyme will soften stiff, cross-linked dermal collagen, the cross-link that matters most is glucosepane, and nothing in this paper touches it. If you are interested in the broader biology of why skin ages, the mechanisms in my articles on senescent "zombie" cells and inflammation testing are at least as relevant.

Can glycation be measured? Which test answers which question?

Parts of it can, but there is no validated "glycation age" test. We can track metabolic exposure, glucose patterns, selected AGE-related signals or local tissue chemistry. Those are different questions, and a useful dashboard labels the layer instead of blending everything into one impressive-looking score.

The useful question is not "What is my glycation score?" It is "Which measurement answers the clinical question I actually have?"

Your questionLayerTestWhat it can revealWhat it cannot prove
Am I developing dysglycemia?Upstream exposure (established clinical testing)HbA1c plus fasting plasma glucose, with or without a 75-g oral glucose tolerance testGlucose exposure or handling in the appropriate clinical contextIt does not directly measure accumulated CML, glucosepane or facial-skin glycation
What happens after meals?Day-to-day glucose patternContinuous glucose monitor (CGM) reviewHow glucose responds to meals, activity and sleepA glucose curve is not a tissue AGE measurement
Can I estimate AGE-related fluorescence?Local optical proxySkin autofluorescenceA non-invasive estimate of fluorescent AGE-related signal in skinCML itself is non-fluorescent, and a local reading is not a whole-body score
Can a named AGE be measured?Named analyteBlood or urine AGE assayThe level of a specific AGE in that sampleIt describes that sample, not the stored burden in your dermis
What is the most direct tissue measure?Local tissue chemistryBiopsySelected local tissue chemistry, directlyIt is invasive, local, and usually a research rather than routine tool

How should glycation measurements be trended?

Trend the same endpoint, and keep the label honest. A repeat measurement can show whether a selected metabolic driver, local proxy or named analyte is moving. It cannot tell you "how fast your whole body is glycating."

  1. Baseline. Choose one clinical question, one method, and note the context that could distort it.
  2. Change. Apply a defined lifestyle, metabolic, photoprotection or skin-treatment plan.
  3. Re-measure. Repeat the same endpoint under comparable conditions at a clinician-set interval.

This is the same logic we use across our diagnostics: measure, intervene, re-measure, and never let one number pretend to explain all of aging.

How do you slow glycation and AGE-related skin aging today?

Make fewer new marks, lower the stress around them, and protect what you rebuild. The strategy today is not glamorous, but it is measurable: reduce avoidable glucose exposure, manage real metabolic disease, remove smoking, sleep, move, protect skin from UV, and use dermatology treatments for the outcomes they have actually been shown to improve.

A practical plan changes measurable exposure and protects future tissue. It does not need to pretend that one habit erases every AGE.

After-meal movement

Movement changes the glucose curve, if it is safe for you. In a small crossover study of 10 inactive adults aged 60 and over with elevated fasting glucose, three 15-minute walks after meals lowered mean 24-hour interstitial glucose on the study day. That is a glucose-pattern result, not tissue age removal.

Food pattern

A nutritious, lower-glycemic pattern is appropriate for many people. A 2021 BMJ systematic review and meta-analysis found that low glycaemic index or load dietary patterns improved glycaemic control in diabetes, and the Diabetes Prevention Program showed that lifestyle intervention reduced the incidence of type 2 diabetes. Cooking method matters too: the dietary AGE literature (Uribarri, 2010) offers a practical guide to reducing AGEs in food, largely by favouring moist, lower-temperature cooking over high-heat browning.

Protect skin

Daily broad-spectrum SPF 30 or higher, plus clothing and shade, is one of the best-evidenced anti-aging steps for skin. A randomized trial (Hughes, Annals of Internal Medicine, 2013) showed that regular sunscreen use helps prevent skin aging. Choosing and layering well is covered in our skincare guidance.

Sleep and smoking

Smoke-free living, adequate sleep and safe regular activity support metabolic control and tissue repair. None of them is exotic. All of them are measurable in effect.

Safety first. If you use glucose-lowering medication or have mobility, foot, cardiovascular, pregnancy, eating-disorder or complex chronic-disease considerations, personalise activity and nutrition with your clinician.

Three buckets

Can CO2 laser or biostimulators remove AGEs from skin?

Not based on current evidence. Resurfacing and biostimulators improve appearance and build new collagen, but that is not proof that old glycation cross-links were cleaved. The cleanest way to think about it is three separate buckets.

BucketWhat is in itBoundary
Today, established: prevent and manageGuideline-based metabolic screening and care; daily broad-spectrum SPF 30+ plus clothing and shade; smoke-free living, safe activity, sleep and nutritionThese lower risk or future injury. They do not prove existing dermal AGE removal.
Today, appearance: remodel and replacePrescription retinoids for photoaging when appropriate; fractional or CO2 resurfacing for selected texture and pigment goals; biostimulators for selected matrix-remodeling goalsImprovement in appearance or new collagen is not proof that old glycation cross-links were cleaved.
Future, experimental: molecular removalCMLase targets one protein modification, CML. Living-tissue delivery and penetration remain unknown. Human safety, dosing, durability and benefit still need trials.There is no approved, commercial, compounded or clinic-delivered CMLase treatment today.

Topical tretinoin has randomized-trial evidence for photoaging, and ablative resurfacing improves selected photoaging endpoints through controlled injury and remodeling. That is why they belong in the "remodel and replace" bucket: you are building new tissue alongside the old, not erasing chemistry from the old. If you are planning a resurfacing procedure, the CO2 recovery guide explains what the weeks afterwards look like, and combination treatments explains how we stack modalities.

Why I am still excited about CMLase

Because it narrows the question. For years the safe assumption was that persistent AGE modifications could only be prevented, diluted through tissue turnover, or worked around. CMLase shows that at least one modification can be enzymatically attacked in laboratory-prepared human tissue. That moves the question from "Is chemistry like this impossible?" to "Can it be delivered safely and usefully in living people?"

That is a meaningful scientific leap, even before it becomes medicine. Getting there still means solving delivery, penetration, dosing, durability, immune reactions, handling of reaction products and toxicology, then proving meaningful benefit in human trials. The developer's own published status (Revel Pharmaceuticals) describes it as research-stage, and that is company-supplied information rather than independent clinical evidence.

Measure, intervene, re-measure. Not one number, one supplement, or one device pretending to explain all of aging.

What does a glycation and skin longevity review look like?

It starts by deciding which question matters first, then tracking the endpoint the intervention is actually supposed to change. In a consultation we choose between, or combine:

Procedure readiness and inflammation sit alongside glucose regulation here. The organism has to heal the skin we treat, which is the theme of skin recovery science.

Frequently asked questions

Did CMLase reverse aging in human skin?

No. The 2026 study lowered a specific CML immunostaining signal in thin fixed skin sections from one older donor after an 18-hour laboratory exposure. It did not treat living people or measure wrinkles, elasticity, biological age, health or longevity.

Did the enzyme make 74-year-old skin younger than 31-year-old skin?

No. The younger material came from a separate donor and was only a staining comparator. There was no matched before-and-after person, no biological-age measurement and no clinical outcome.

Can I get CMLase now?

No approved or commercial CMLase treatment is available. Delivery, penetration, dosing, durability, immune reactions, reaction-product handling, toxicology and meaningful benefit still require preclinical and human study.

Can I test my glycation?

Different tests answer different questions. HbA1c, fasting glucose, OGTT and CGM assess glucose exposure or handling. Skin autofluorescence is a local optical proxy. Blood or urine assays can measure a named AGE in that sample. A biopsy can directly measure selected local tissue chemistry. None is a validated whole-body glycation-age score.

Do CO2 laser or biostimulators remove AGEs?

Not based on current evidence. Resurfacing can improve selected photoaging endpoints through controlled injury and remodeling, and biostimulators can support selected matrix-remodeling goals. Those outcomes do not prove that established CML or glucosepane was cleaved.

What should I do about glycation today?

Start with established care: evaluate dysglycemia when indicated, avoid smoking, support safe activity and sleep, choose a nutritious lower-glycemic pattern when appropriate, use broad-spectrum sun protection, and select evidence-based dermatology treatments for specific visible goals. A consultation can determine what is worth measuring and re-measuring for you.

Verifiable sources

The CMLase data are preclinical and ex vivo: one skin donor, fixed tissue, a staining endpoint. The walking study is small (n = 10) and measured one day of glucose. Company status information is not independent clinical evidence.

Where this fits at Sajic Longevity. We do not offer CMLase, because nobody can. What we do offer is a physician-led review that picks the right glycation layer to measure, pairs it with skin imaging and procedure planning, and re-measures the same endpoint after the plan has had time to work. Book a consultation or call 1-888-430-4665.