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

Scientific concepts, discoveries, and nature/biology phenomena

1) Advanced glycation end products (AGEs) and “molecular rust”

• Glycation (age-related damage) has long been described as irreversible in textbooks.
• CML (carboxymethyllysine) is highlighted as one of the most common AGEs.
• CML is associated with:
  • Wrinkles (skin aging)
  • Stiff arteries (vascular aging)
  • Atherosclerotic plaque formation (pathology risk)
• Mechanistic framing:
  • CML can accumulate for decades on long-lived proteins (updated slowly), such as:
    • Collagen (skin and arteries)
    • Proteins in the eyes and kidneys
  • CML is described as “molecular rust” because it is stable and protein-bound, making it hard to remove.
• Reported gap before this work:
  • No known effective enzyme could convert stable protein-bound CML back to normal lysine.

2) Discovery: engineered bacterial enzyme (CMLase) that reverses CML

• A new study (Nature Communications, July 2026) is presented as showing reversal/removal of CML.
• Starting point:
  • The researchers began with bacterial glycine oxidase–type enzymes.
  • Some variants could remove free-state CML, but not CML attached to peptides/proteins.
• Key engineering strategy:
  • Screened enzyme diversity to find a structure with a more open active site allowing larger protein fragments to access the active site.
  • Reported search scope: >44,000 enzyme structures.
  • Then performed massive directed evolution/optimization:
    • Screened >500 million modified versions.
  • Selection criterion:
    • Bacteria were allowed to survive only if the enzyme successfully converted CML back to normal lysine.
  • After five engineering rounds, the final enzyme was named CMLase.
• Reported biochemical outcome:
  • CMLase contains 15 amino acid substitutions and two amino acid deletions relative to the starting enzyme.
  • It removes the chemical group from damaged lysine and restores lysine.

3) Experimental evidence reported

• In vitro lab tests on proteins (overnight treatment):
  • CML reduction ranges:
    • 52–97% reduction in detectable CML in:
      • Albumin
      • Collagen
      • Casein
      • Hemoglobin
      • Sheep eye-isolated proteins
  • Mass spectrometry mapping:
    • CML detected at 33 locations on albumin.
    • CMLase reduced CML at 30 of those sites.
    • Improvements:
      • >50% improvement in 21 locations
      • >90% improvement in 7 locations**
• Ex vivo preserved human tissues (one donor per tissue type; not a clinical trial):
  • Lens proteins (64-year-old donor):
    • 45% decrease by mass spectrometry
    • 78% decrease by antibody test
  • Aorta sections (75-year-old donor):
    • >70% reduction in CML staining
  • Skin (74-year-old donor):
    • >55% reduction in CML staining
    • Reduced to a level reportedly below what was measured for skin of a 31-year-old donor
  • All effects described as occurring after one night, but not in living organisms.

4) Limitations / what the study does NOT yet prove

• Not clinical evidence:
  • “n = 1” style limitations (one donor per tissue type; multiple sites per donor).
• Ex vivo constraints:
  • Preserved tissue in a dish has no blood flow, no living immune system, and no full physiological response.
• No functional endpoints shown:
  • No direct evidence of improved arterial elasticity, eye function, reduced inflammation, or increased life expectancy.
• Delivery problem remains:
  • The enzyme was not introduced into the actual living extracellular matrix.
  • Future in-body use may trigger immune reactions.
• AGE specificity:
  • The work focuses on CML only, not other AGEs (e.g., glucosepane, noted as a major crosslinking AGE in aging collagen).

5) “How to use the knowledge” (lifestyle/biochemistry concepts)

While the enzyme is not usable yet, the video discusses ways to reduce AGE formation, centered on glycemic control and cooking chemistry.

A) Blood sugar regulation as a driver of glycation

• Hyperglycemia can increase circulating/intracellular AGEs including CML.
• Direct AGE measurement is said to be difficult; HbA1c (hemoglobin A1c) is used as an indirect marker.
• Claim: carbohydrate intake alone doesn’t automatically cause glycation; the key is insulin sensitivity.

B) Strength training and glucose uptake

• Exercise (especially strength training) increases muscle glucose uptake.
• Strength training is presented as indirectly helpful for reducing glycation/AGE burden and for skin rejuvenation.

C) Timed eating / intermittent fasting

• Example schedule given:
  • First meal ~10:00
  • Second meal ~16:00–17:00
• Claim: keeping glucose lower for more of the day supports longevity pathways (as described in the video).

D) Cooking methods and AGE formation

• High-temperature dry cooking (reported):
  • frying, broiling, baking → more AGEs
• Moist-heat methods (reported to create fewer AGEs):
  • boiling, steaming, simmering, braising
• Dietary AGE concentration claims:
  • Meats and fats cooked at high temperatures have the highest AGE levels.
  • Grilled/barbecued/deep-fried foods: most AGEs.
• Absorption estimate:
  • Dietary AGEs: only ~10% absorbed (per the video), but can still add up.

E) Antioxidants to counter AGE effects

• Suggestions:
  • Pair high-AGE foods with antioxidant-rich vegetables
  • Examples mentioned: vitamin C, vitamin E

6) Supplements and trials mentioned (general glycation rather than CML specifically)

• Collagen and glycine are presented as helpful for lowering AGE-related measures.

2023 randomized controlled trial: marine collagen peptides

• 5 g marine collagen peptides for 12 weeks
• AGE change:
  • Collagen group: ~4.7% decrease
  • Placebo group: ~4.85% increase
• Insulin sensitivity:
  • HOMA-IR decreased by:
    • ~18% in collagen group
    • ~10% in placebo group
• AGE changes correlated with HOMA-IR changes.

Glycine in type 2 diabetes

• 5 g glycine three times daily
• HbA1c improvement:
  • Glycine group: from 8.3% → 6.9%
  • Placebo: from 8.0% → 7.6%
• Claim/interpretation:
  • Glycine status is lower in people with higher HbA1c.

Meal-level glycemic effect

• A single dose: 5 g glycine + 25 g glucose
• Result claimed: >50% reduction in postprandial glucose response vs glucose alone.

Proposed role of glycine

• Glycine may help regulate blood sugar and reduce glycation/AGE formation.

Additional glycine claims (as stated)

• Raises glutathione
• Neutralizes harmful effects of methionine on longevity (as claimed)
• Supports creatine synthesis

Herbs mentioned for cooking-related AGE reduction

• rosemary, thyme, parsley
• Use suggested as a topping when cooking high-temperature meat

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Researchers / sources featured

• Researchers in a Nature Communications study (July 2026) (the video does not name individuals)
• Journal source: Nature Communications (July 2026)
• Mentioned experimental targets/sources (organisms/materials):
  • Bacterium: Calidithe Thermos Rosius (as written in subtitles; likely intended as a specific bacterial source for the enzyme)
  • Human tissue donors (ages mentioned): 64-year-old lens donor, 75-year-old aorta donor, 74-year-old skin donor, plus 31-year-old comparison skin (no names provided)
• Clinical trial sources (no investigator names given in subtitles):
  • 2023 randomized controlled trial on marine collagen peptides (5 g for 12 weeks)
  • Type 2 diabetes glycine trial(s) (no named authors/affiliations provided)
  • A postprandial glucose study with glycine + glucose (no named authors/affiliations provided)