A new study has shown that an engineered enzyme can remove a specific form of age-associated chemical damage from proteins in human tissues.

First, the simple explanation

As we get older, our bodies gradually accumulate small amounts of damage. Some of that damage happens to the proteins that help build our tissues — including the proteins in our skin, blood vessels, eyes and connective tissues.Think of these proteins a little like the structural  materials in a building.

When they are new, they are organised and able to do their jobs properly. But over many years, chemical changes can gradually build up on them. One of these changes is caused by glycation.

Glycation happens when sugars and other reactive molecules attach themselves to proteins without the body deliberately controlling the process.

Over time, some of these reactions produce substances known as advanced glycation end products, or AGEs. AGEs tend to accumulate as we get older, particularly in proteins that remain in the body for a long time.

So what did the researchers do?

Scientists have now engineered an enzyme that can remove one particular type of AGE-related damage from proteins. The damaged molecule they targeted is called CML.

In laboratory experiments, the researchers treated proteins and samples of older human skin, artery and eye tissue with the enzyme. The amount of CML in those samples fell substantially.

In other words, rather than simply trying to prevent further damage, the scientists were able to remove some damage that had already accumulated. And that is what makes this study interesting.

Does that mean they reversed ageing?

No. This is the most important point. Some reports about this research have suggested that scientists made old tissue “younger” or reversed decades of ageing. That is not what the study showed.

The researchers removed one particular chemical modification from proteins. They did not show that the whole tissue became young again. They did not show that an old artery became as flexible as a young artery. They did not show that old skin regained youthful structure or function.

And the enzyme has not been used as an anti-ageing treatment in people.

Ageing involves hundreds of interconnected changes throughout our cells and tissues. Removing one type of molecular damage is therefore very different from reversing ageing itself.

So why is the study exciting?

Because it raises an important possibility. Most discussions about healthy ageing concentrate on trying to slow down damage. Eat well. Exercise. Don't smoke. Control blood glucose. Sleep properly. Reduce unnecessary metabolic stress. All of those approaches remain important.

But researchers are now beginning to ask another question: What if some of the damage that has already accumulated could actually be repaired?

This study suggests that, at least for one very specific form of protein damage, that might be possible. That does not give us an anti-ageing treatment today, but it introduces a fascinating idea for future medicine: instead of only slowing damage, we may eventually be able to identify particular forms of molecular damage and repair them directly.

For Those Who Want the Science. What is glycation?

Proteins in the body are continually exposed to sugars and other reactive molecules. Some of these can react spontaneously with amino acids in proteins through a process known as non-enzymatic glycation.

Over time, these reactions can generate a diverse group of chemically modified structures known as advanced glycation end products, or AGEs. AGEs are particularly relevant in proteins that remain in the body for long periods, including components of the extracellular matrix such as collagen.

Rather than being a single substance, “AGEs” describes a large and chemically varied family of modifications. That distinction matters because different AGEs can have different biological effects. Some may change the structure or turnover of proteins. Some AGE-related modifications and crosslinks may contribute to changes in tissue stiffness and elasticity, while others can participate in cellular signalling and inflammation.

CML: one particular AGE

The researchers focused on Nε-carboxymethyl-lysine, or CML. CML forms when a lysine residue within a protein becomes chemically modified. It accumulates in long-lived proteins with age and has been identified in tissues including the skin, vascular wall and eye. CML is also potentially important because it can interact with the receptor for advanced glycation end products — RAGE.

Activation of RAGE can influence inflammatory signalling pathways, including NF-κB. This creates an interesting possible connection between accumulated molecular damage and changes in inflammatory signalling.

However, it is important to distinguish a plausible mechanism from a proven therapeutic effect: this study did not demonstrate that removing CML from living human tissues reduces RAGE signalling or inflammation.

Could an enzyme remove CML?

The researchers set out to engineer an enzyme capable of recognising and removing CML that had already formed on proteins. They began with enzymes known as glycine oxidases and used computational approaches followed by directed evolution.

Directed evolution involves generating large numbers of enzyme variants and repeatedly selecting those that perform the required task most effectively. Through this process the researchers developed an engineered enzyme referred to as CMLase, or CrGO-897.

The enzyme acquired the ability to act upon CML attached to peptides and proteins. Most interestingly, it could chemically convert the modified CML residue back towards the original amino acid, lysine.

This is why the research can be considered an example of direct molecular repair. The goal is not merely to stop further damage forming. It is to repair a molecular modification that is already present.

What happened when they tested human tissue?

The researchers tested the enzyme on proteins and human tissue samples containing CML that had accumulated naturally over many years. Experiments included proteins from human lens tissue and samples of older human arterial and skin tissue. Treatment substantially reduced measurable CML.

This provides proof of principle that CML accumulated in aged human proteins is not necessarily chemically irreversible.

But this was not rejuvenation

This is where interpretation becomes extremely important. If an old tissue sample contains more CML than a young tissue sample, and treatment reduces CML to the level seen in younger tissue, we cannot conclude that the entire tissue has become biologically young.

CML is simply one measurement. Ageing also involves changes in:

• mitochondrial function;
• DNA and epigenetic regulation;
• cellular senescence;
• immune activity;
• extracellular-matrix organisation;
• vascular function;
• stem and progenitor-cell activity;
• protein quality control;
• cellular communication; and
• tissue repair and regeneration.

Removing one molecular lesion does not automatically restore all of these systems.

CML is also not the same thing as all AGE damage

The term AGE describes many different chemical modifications. CML is only one of them.

Other glycation-derived structures may influence tissue ageing differently. Some are capable of forming chemical crosslinks between proteins, which may be particularly important in long-lived extracellular-matrix proteins such as collagen.

One important example is glucosepane, which accumulates in ageing human tissues.

An enzyme capable of removing CML therefore cannot automatically be described as an enzyme that “removes AGEs”. It removes a particular AGE-related modification. That distinction is scientifically important.

Did removing CML improve the tissue?

We do not yet know. The researchers demonstrated that they could remove CML chemically.

They did not establish that this restored normal tissue function.

For example, the study did not demonstrate that treated arteries became more elastic or that treated skin regained youthful mechanical or biological properties. Nor did it show improvement in organ function. These are important questions for future research.

A molecular repair becomes clinically meaningful only if repairing that molecule produces a useful improvement in the functioning of the cell, tissue or organism.

Could this enzyme currently be given to people?

No. The human tissue experiments were performed outside the living body. This is known as ex vivo research. Using an enzyme inside a living person would create additional challenges.

The enzyme would need to:

• reach the right tissues;
• penetrate deeply enough to find CML-modified proteins;
• remain active for long enough to work;
• avoid damaging other molecules;
• and do so without producing unacceptable immune or other adverse reactions.

The engineered enzyme is derived from a bacterial protein, so potential immunogenicity would be one of several safety questions requiring careful investigation.

There are currently no clinical trials demonstrating that CMLase can safely reverse tissue ageing in humans.

Where might this lead?

This study is best viewed as proof of concept for molecular repair. It suggests that some chemical modifications traditionally regarded as accumulated molecular damage may eventually become therapeutic targets.

The next questions are much harder:

• Can the enzyme work inside living tissue?
• Can it reach enough of its target?
• Does removing CML improve tissue physiology?
• Does it reduce harmful signalling?
• Does it improve health?
• And can it do all of this safely?

Only animal studies and eventually carefully controlled human trials can answer those questions.

The Wildberry Perspective

This study does not show that scientists have discovered a treatment that reverses ageing.

But neither should its importance be dismissed. It demonstrates something conceptually important: a chemical modification that accumulates on ageing human proteins can be deliberately targeted and removed.

That represents a different approach to ageing biology. Instead of thinking only about how we might slow the accumulation of molecular damage, researchers are beginning to explore whether some forms of damage that are already present could eventually be repaired.

The important distinction is between repairing a molecule and rejuvenating an organism.

This research has demonstrated the first. Whether direct molecular repair can eventually contribute to restoration of tissue function, resilience and ultimately healthier ageing remains one of the fascinating questions for the future of ageing medicine. But the study also raises a complementary question:Can we reduce the formation of this type of protein damage before it accumulates in the first place?

This is where nutrition, metabolic health and potentially botanical medicine become particularly interesting. Herbal medicines and plant compounds cannot currently be said to reverse established CML damage in the way this engineered enzyme did. However, several botanicals and their constituents have shown promising antiglycation activity in experimental research.

Rather than acting at one single point, they may potentially influence several stages in the process by which proteins become damaged.

1. Reducing the metabolic pressure that drives glycation

Glycation is influenced partly by the amount and duration of exposure of proteins to glucose and other reactive sugar-derived molecules.

Supporting healthy glucose regulation and insulin sensitivity may therefore reduce some of the metabolic conditions that favour excessive glycation.

This may be relevant to botanicals such as cinnamon and berberine-containing plants, although it is important to distinguish their effects on glucose metabolism from evidence of a direct antiglycation effect on proteins.

In other words, improving the metabolic environment may help reduce the amount of new damage being generated.

2. Trapping reactive carbonyl compounds before they damage proteins

Glycation does not occur only through glucose attaching directly to proteins. During normal metabolism, highly reactive compounds known as reactive dicarbonyls can also form. One of the most important is methylglyoxal.

Methylglyoxal is considerably more reactive with proteins than glucose itself and can contribute to the formation of advanced glycation end products.

Experimental research suggests that compounds found in turmeric, particularly curcumin, and cinnamon, including certain procyanidins, may help trap or scavenge some of these reactive intermediates before they modify proteins.

This represents an interesting form of molecular protection: intervening before a damaging chemical reaction becomes fixed into the protein.

3. Supporting the body's own detoxification systems

The body already possesses mechanisms for dealing with reactive carbonyl compounds such as methylglyoxal.

One of the most important is the glyoxalase system, particularly the enzymes GLO1 and GLO2.

This system helps convert methylglyoxal into less reactive compounds before it can extensively modify proteins.

In experimental studies, curcumin has influenced glyoxalase-1 activity and expression. This raises the possibility that some botanical compounds may work not simply by acting as antioxidants themselves, but by supporting endogenous cellular damage-control systems.

This is an important distinction. Rather than thinking of herbs simply as substances that “neutralise free radicals”, we can begin to ask whether particular plant compounds influence the body's own mechanisms for detecting, processing and limiting molecular damage.

4. Protecting proteins while glycation is occurring

Rosemary, and particularly its constituent rosmarinic acid, is especially interesting from this perspective. Experimental research has shown that rosmarinic acid can reduce methylglyoxal-induced glycation of human proteins and also reduce protein aggregation.

That matters because protein ageing is not simply about the presence of a chemical marker.

A modification may alter the way a protein folds, interacts with other proteins, or maintains its normal structure.

Protecting the structural integrity of a protein while limiting glycation may therefore be biologically more meaningful than simply reducing a laboratory marker of oxidative stress.

5. Reducing the biological consequences of AGE accumulation

Preventing every AGE from forming is unlikely to be possible. But even when advanced glycation end products have accumulated, their biological consequences may potentially be modified.

Some AGEs interact with the receptor for advanced glycation end products, or RAGE, which can activate downstream pathways including NF-κB and contribute to inflammatory signalling.

Phytochemicals such as curcumin have influenced AGE/RAGE-related signalling experimentally.

This means botanical intervention may potentially occur at another level: not necessarily removing the AGE itself, but reducing some of the inflammatory signalling associated with its presence.

Prevention and repair are not the same thing

This distinction is crucial. The engineered CMLase used in this study represents an experimental form of direct molecular repair: it acted on an existing CML modification and removed it.

The botanical research described above is different. Rosemary, cinnamon, turmeric and other plant compounds appear more likely to work by reducing the conditions that allow damage to form, intercepting reactive molecules, supporting endogenous detoxification systems, protecting protein structure, or modifying the biological response to accumulated AGEs.

These mechanisms are scientifically interesting, but most of the direct antiglycation evidence remains experimental or preclinical. We cannot currently say that taking these herbs prevents age-related protein glycation in humans, removes established CML from human tissues, or rejuvenates aged extracellular matrix.

What the research does suggest, however, is a broader and potentially important therapeutic concept. Future approaches to healthy ageing may ultimately involve both sides of the process:

reducing the creation of new molecular damage while developing ways to repair selected forms of damage that have already accumulated.

From a Wildberry perspective, this is particularly interesting because it shifts the discussion away from the idea of a single “anti-ageing” substance. Instead, it invites us to think about ageing as an ongoing relationship between damage, defence, repair and biological organisation — and to ask how nutrition, metabolism, botanical medicine and future molecular technologies might each contribute at different points within that system.

References

1. Trabosh N, Smith J, Hsu MYH, et al. Reversal of protein chemical aging by enzymatic deglycation. Nature Communications. 2026;17:5926. doi:10.1038/s41467-026-75141-2.
   — The central study describing the engineered CMLase/CrGO-897 enzyme and removal of CML from proteins and human tissue samples.
2. Shamsi A, Ahmed A, Khan MS, Husain FM, Bano B. Rosmarinic acid restrains protein glycation and aggregation in human serum albumin: Multi spectroscopic and microscopic insight. International Journal of Biological Macromolecules. 2020;161:187–193.
   — Supports the discussion of rosmarinic acid, protein glycation and protection against glycation-associated protein aggregation.
3. Peng X, Cheng KW, Ma J, et al. Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts. Journal of Agricultural and Food Chemistry. 2008.
   — Supports the proposed role of cinnamon polyphenols, including procyanidins, in trapping reactive carbonyl compounds involved in AGE formation.
4. Peng X, Ma J, Chao J, et al. Beneficial effects of cinnamon proanthocyanidins on the formation of specific advanced glycation endproducts and methylglyoxal-induced impairment on glucose consumption. Journal of Agricultural and Food Chemistry. 2010.
   — Examined cinnamon constituents against specific AGEs, including CML and methylglyoxal-derived AGEs.
5. Ishikawa M, Taniguchi R, Taniguchi T, Yang Z, Nishikata T. Re-evaluation of the anti-glycation activity of herbal extracts using multiple anti-glycation assays. Bioscience, Biotechnology, and Biochemistry. 2026.
   — Particularly relevant to Cinnamomum, Pueraria and Coptis, and useful because it distinguished activity during glycation from effects observed when extracts were added after glycation-related modifications had already developed.
6. Cardoso FN, Dos Santos Nunes EV, Figueiredo ID, et al. Cissus verticillata leaf extract decreases the production of AGEs and ROS in vitro. Molecules. 2026;31(4):697. doi:10.3390/molecules31040697.
   — Emerging evidence for Cissus verticillata, including inhibition of AGE formation, protein carbonyl formation and glycoxidative stress.
7. Amin A, Ávila-Quezada GD. Polyphenol-based modulation of the Glo1–Nrf2–RAGE axis in diabetes and neurodegeneration: mechanistic evidence, translational constraints, and critical appraisal. Frontiers in Pharmacology. 2026;17:1877182. doi:10.3389/fphar.2026.1877182.
   — Useful mechanistic review for curcumin and other polyphenols, particularly their potential influence on glyoxalase-1, Nrf2 antioxidant defence and AGE/RAGE inflammatory signalling.
8. Li M, Zhang C, Ma J, et al. Curcumin attenuates liver injury by modulating the AGE-RAGE axis and metabolic homeostasis in high-fat diet/streptozotocin-induced type 2 diabetic mice. Frontiers in Nutrition. 2025;12:1710380. doi:10.3389/fnut.2025.1710380.
   — Preclinical support for curcumin’s effects on AGE–RAGE, NF-κB and metabolic/inflammatory signalling; this should not be interpreted as evidence of AGE removal in humans.
9. Kim J, Kim KM, Kim CS, et al. Protective effects of Puerariae radix extract and its single compounds on methylglyoxal-induced apoptosis in human retinal pigment epithelial cells. 2014.
   — Supports the discussion of Pueraria/kudzu in relation to methylglyoxal-associated glycation stress.
10. Ghodsi R, Kheirouri S. Carnosine and advanced glycation end products: a systematic review. Amino Acids. 2018;50(9):1177–1186. doi:10.1007/s00726-018-2592-9.
    — Useful supporting reference for the optional discussion of carnosine as a nutritional antiglycation compound. Human evidence remains much more limited than the laboratory and animal evidence.
11. Tanwar V, Kapahi P, Newman JC, Stubbs B. Reduction of glycation stress as a geroscience intervention: protocol for a pilot RCT in postmenopausal women. npj Aging. 2026. doi:10.1038/s41514-026-00373-x.
    — The GRACE trial, testing the GLYLO formulation containing alpha-lipoic acid, nicotinamide, pyridoxine, benfotiamine and piperine against AGEs and methylglyoxal in postmenopausal women. This is currently a trial protocol, not evidence of efficacy. 

Clinical herbal medicine grounded in science and individualised care.