This Enzyme Made 74-Year-Old Skin Tissue 30 Again

For decades, the textbooks said that this type of aging damage, called glycation, was irreversible. It contributes to wrinkles, stiffens your arteries, and may promote atherosclerotic plaque. This is CML, carboxymethyllysine, and it's one of the most abundant advanced glycation end products, or AGEs. In a new study, a bacterial enzyme erased 70% of it from a 75-year-old human artery overnight. The levels of glycation in skin of a 75-year-old dropped to those of someone in their 30s. Glycation isn't just bad for wrinkles. CML can accumulate for decades on long-lived proteins that turn over very slowly. The collagen in your skin and arteries, the proteins in your eyes, and in your kidneys. Your body has systems that neutralize some of the glycation precursors before the damage forms, but there's no known efficient enzyme to turn stable CML back into normal lysine. This CML is basically like molecular rust on these proteins. You can't simply wash it off. Until this study, stable protein-bound CML was considered effectively irreversible. So in this video, I'm going to break down this new discovery and what it means for not only potential skin anti-aging, but for general longevity, and how you can utilize this knowledge. Let's start with a new study published in the journal Nature Communications in July 2026. The researchers began with bacterial enzymes called glycine oxidases. One of these enzymes could remove CML when it was floating freely, but it couldn't reach CML attached to a peptide or protein. So they searched for more than 44,000 enzyme structures for one with a more open shape. They found an enzyme from the bacterium Chalidithermos roseus that had more space around its active site, which allowed larger protein fragments to enter. But the enzyme was still extremely weak. The researchers then screened for more than 500 million modified versions of it. They designed the experiment so that bacteria could survive only when an enzyme successfully converted CML back into normal lysine. After five rounds of engineering, they created the final enzyme called CMLase. Compared to the original enzyme, it contained 15 amino acid changes and a 2-amino acid deletion. CMLase removes the chemical group attached to the damaged lysine and restores it to normal lysine. First, they tested it on proteins in the laboratory. After overnight treatment, CMLase reduced detectable CML by 52-97% across albumin, collagen, casein, hemoglobin, and protein extracted from sheep eyes. Mass spectrometry found CML at 33 different sites on albumin. The enzyme CMLase reduced CML at 30 of those sites. 21 sites improved by more than 50%, and 7 improved by more than 90%. Then they tested this CMLase in preserved human tissue. In proteins from the eye lens of a 64-year-old donor, CML dropped by 45% when measured directly using mass spectrometry. An antibody test found a larger 78% reduction. In preserved aorta sections from a 75-year-old donor, CML staining fell by more than 70%. And in skin from a 74-year-old donor, CML staining fell by more than 55%, to less than the levels measured in skin from a 31-year-old donor. All after one overnight treatment. But remember this happened in a dish, not inside a living person. Now this sounds quite interesting, but unfortunately a lot of headlines can be a bit misleading. Number one, the headline human experiments used single donors per tissue. They're basically N equals 1 for the main lens, aorta, and skin, not a clinical trial. The four aorta measurements were four spatial regions, not four people. Two, it's preserved tissue in a dish, not living animal tissue, and not living human tissue. There was no blood flow, no intact immune system, and no real world results were achieved. Three, there's no data on function. They didn't show arteries become more elastic, the eyes becoming more efficient, lower inflammation, or increased lifespan. Four, they didn't deliver this bacterial enzyme into a real human extracellular matrix. This is important because if you inject it into a real human, you could develop an immune reaction. Five, CML is only one advanced glycation end product. The study didn't look at others, such as glucosepine, the dominant AGE that cross-links in aged human collagen. So this study doesn't prove that CMLase reverses human aging or skin aging, but it does prove that it is possible to reverse one type of age-related damage which was previously thought to be irreversible. Now of course you can't really use this knowledge at the moment. You can't inject yourself with this CMLase at the moment, but there are still ways to reduce the formation of CML and other AGEs even today. Number one, maintain healthy glucose regulation. Experimental hyperglycemia can increase circulating or intracellular glycation products, including CML in humans. It's going to be very hard to measure CML or other types of glycation, but you can measure glycated hemoglobin or hemoglobin A1c, which can be an indirect marker of glycation status. Pre-diabetes is 5.8 percent. Mine sits around 4.5 percent, which is extremely low despite me eating over 300 grams of carbs a day. So just eating carbohydrates doesn't cause glycation. It matters in the context of who is eating it and how good is their insulin sensitivity. If you have very good insulin sensitivity, then even eating a lot of carbohydrates isn't going to cause glycation because your body effectively metabolizes the glucose. You could be eating a low-carb diet and still have a hemoglobin A1c of 5.3 percent or 5.5 percent, which is quite close to pre-diabetes. Having a hemoglobin A1c of 5.3 percent causes a lot more glycation than 4.5 percent. And if you know your hemoglobin A1c but don't know how good it actually is, then take my 3-minute health percentile assessment in my top 1% health community. It puts your hemoglobin A1c into perspective and scores it alongside your other biomarkers and fitness metrics to show you your overall health percentile. If you don't have blood work done, then you can still get your health score with 3 metrics. I'll leave the link down below. How can you achieve better blood sugar regulation? The biggest determinant of that is resistance training because muscles soak up an insane amount of blood sugar if you exercise. Try lifting weights about 3-4 times a week. It's no coincidence then that resistance training has been seen to rejuvenate skin in humans. Of course, if you become a bodybuilder, you eat a ton of food, you take steroids, you have sleep apnea, then your skin is going to age faster. But it doesn't have to be you. You can just lift weights like a normal person. Another useful thing is time-restricted eating or intermittent fasting. I have my first meal at 10am and my second meal at 4-5pm. This means that for the rest of the day, my blood sugar is quite low. I have plenty of energy because of metabolic flexibility, and my blood sugar is especially low during my sleep, which is when a lot of the longevity pathways get activated. Secondly, it's important how you cook. Dry, high heat, frying, broiling, grilling, and roasting creates a lot more dietary AGEs, especially in animal foods that are rich in protein and fat. Moist heat, boiling, steaming, poaching, and stewing creates a lot less of them. Here's a list of foods with the most AGEs. As you can see, high temperature cooked meats and fats have the highest AGEs. Bacon is even higher in AGEs than deep fried french fries. But basically, anything that's barbecued, grilled, or deep fried has the most AGEs. Foods that are naturally higher in protein, even if eaten raw, still have higher AGEs than carbohydrates and fiber sources, even if those carbohydrates and fiber sources are cooked. That's because of the lower protein content. It is true that dietary AGEs aren't absorbed 100%. It's estimated that you only absorb around 10% of the dietary AGEs you get from the food. But 10% can still accumulate, especially if you eat a lot of bacon and a lot of barbecue. So I wouldn't go crazy with it, but try to minimize high temperature and high heat cooking. The biggest harm you want to be aware of is deep frying. But any form of barbecue and any form of super high temperature cooking is generally going to create a lot more AGEs. You also want to consume various antioxidants from your food to counteract the AGEs, such as vitamin C, vitamin E, etc. That's why if you eat barbecue or something, pair it with plenty of vegetables to support the antioxidant defense system. Are there any supplements that reduce CML or other AGEs? Not CML specifically, but general collocation, yes. They're mostly collagen and glycine. In this 2023 randomized controlled trial, taking 5 grams of marine collagen peptides for 12 weeks was seen to result in 4.7% lower AGE levels from baseline, whereas the placebo group saw a 4.85% increase in AGEs. Their HOMA-IR, which is a marker of incident sensitivity, also decreased by 18% in the collagen group and by 10% in the placebo group. The change in AGEs was strongly correlated to the decrease in HOMA-IR. The reason why collagen reduces AGEs is because of glycine. As I said, most people aren't able to directly measure their AGEs, but you can estimate it by measuring your hemoglobin A1c. In type 2 diabetics, supplementing 5 grams of glycine 3 times a day reduced hemoglobin A1c by about 1% more than placebo, from 8.3% to 6.9% in the glycine group versus 8% to 7.6% in the placebo group. The percentage refers to hemoglobin A1c percentage. In people with type 2 diabetes, individuals with a hemoglobin A1c over 9% have significantly lower glycine status than those with a hemoglobin A1c below 6%. It doesn't necessarily mean that low glycine causes diabetes, but it means that glycine is certainly soaked up in diabetes. Raising glycine status can help to reduce blood sugar and glycation. Even a single ingestion of 5 grams of glycine in one sitting with 25 grams of glucose in a drink has been seen to reduce the post-meal glucose response by over 50% compared to glucose alone. All of this suggests that glycine has an important role in blood sugar regulation and preventing glycation. So adding glycine to your meals is not only good for skin by increasing collagen, but also by reducing glycation. And glycine has a lot of other benefits as well. It increases glutathione, counteracts the harmful effects of methionine on your longevity, and even supports creatine synthesis. So you can take glycine pretty much throughout the day. There are a few other things that can reduce glycation. Different types of herbs like rosemary, thyme, parsley. If you're cooking, like making some sort of high temperature cooking with your meat, add some of these herbs on top of that. That's also going to reduce the formation of these AGEs. Of course, it's not going to completely nullify the AGEs, but at least you're doing something to reduce the amount of them. And then add glycine on top of that. All right, let's wrap it up. This is good news because for decades, scientists thought that CML was irreversible. It just accumulates in the cells and tissue, and that leads to aging damage over time. But this new bacterial enzyme has shown that it can reverse it, even up to 70%. It's not a drug yet. It's not a supplement yet. It's not available. So right now you still need to follow a lifestyle that minimizes AGE formation. Number one, the biggest determinant is having good blood sugar levels and having lower hemoglobin A1c. And the second part is having a diet that is lower in the AGEs, but the biggest determinant is still your blood sugar and hemoglobin A1c. And while you can't easily measure CML yourself, you can measure any of the other biomarkers that tell you how healthy you actually are, including your glycation status. I've built a three-minute health percentile assessment that puts them all into perspective and shows you what to improve first. It's in my top 1% health community, linked down below.