Newly developed enzyme can reverse skin age from 70+ years to 31 years

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I'm a cardiologist. Everyone is sharing this study as a skin story. They're burying the part that matters.
Scientists took the aorta of a 75-year-old donor, applied a single engineered enzyme, and stripped away more than 70% of the molecular damage — bringing it down to the levels you'd see in a 30-year-old artery.
Published five days ago in Nature Communications. Revel Pharmaceuticals, with Calico and the University of Colorado.
Here's what they erased.
Sugar reacts with proteins in your body the same way heat browns bread — slowly, over a lifetime. It leaves behind a residue called CML, the most abundant advanced glycation end product in aging tissue. It welds itself onto collagen and elastin in your skin, your eye lens, and your arterial walls.
Two things follow. Your arteries stiffen. And CML latches onto a receptor called RAGE, which drives chronic inflammation — the exact fire I've been writing about for months as the engine of heart disease.
Since the 1980s this damage was considered permanent. Your body has no enzyme to remove it. Every existing approach only slows new damage from forming. Nothing touched what was already there.
So they built an enzyme that doesn't exist in nature. They screened 45,000 protein structures, then ran five rounds of directed evolution across more than 500 million variants until they had CMLase — a molecular lawnmower that oxidizes the CML off the protein and restores the original, healthy lysine underneath.
Not patched. Reversed.
Over 70% cleared from elderly arterial tissue. Over 55% from elderly skin — below the levels found in 31-year-old skin. 45-78% in lens proteins. The CEO said they expected 20% and were floored.
Arterial stiffness drives systolic hypertension, heart failure, and stroke, and I have no drug that reverses it. I can slow the process. I cannot undo it. This paper says undoing it may be possible.
The caveats are real and I won't skip them. This was done on donated tissue in a dish, not in a living person. No functional data yet — we don't know if that artery got measurably more elastic. Delivering a large enzyme deep into human tissue is a hard, unsolved problem. Clinical trials are years away.
But something considered permanent for forty years just came off human tissue.
We spent a century learning to slow aging. Someone finally figured out how to erase it.
Thank you @theallinpod @friedberg @chamath @pesottas

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Friedberg: New study shows enzyme reverses skin age from 70+ years to 31

Chamath: That’s a $2T market.

Did Scientists Just Discover How to Reverse Skin Aging!?

“CML is kind of the predominant molecule that gets formed in this extracellular matrix that's driving aging, and nothing breaks it down.

So these scientists set out to try and create an enzyme, an enzyme is a protein that breaks something down, that can break down CML.

And so these guys kind of went out and they took the target, which is CML, and tried to figure out, ‘Okay, how do we actually degrade CML, clear that extracellular matrix, and reverse aging?’

They started to test it on the proteins that we would find in our body, casein, collagen, retinal proteins, which are in your eye, hemoglobin, and they were able to get rid of 52 to 97% of the CML, just degrade it away.

And then they found several sites where they were able to degrade over 90%.

And then they took actual human skin from elderly patients that had donated their skin, and they put this enzyme onto that skin, and they were able to eliminate 55% of the CML on the skin, basically reverse the skin's age down to the age of a 31-year-old, this is from greater than 70-year-old patients, just by putting this enzyme on the skin.

And so it's kind of a groundbreaking demonstration of combination of AlphaFold, what's called directed evolution, where you change the order of the DNA that changes the structure of the protein to test different proteins, do high throughput screening, and ultimately make a novel protein that doesn't exist in nature today that can do something pretty profound for human health.”

Chamath:

“It will be a trillion-dollar market. If you can create a cream…”

Friedberg:

“I mean, dude, if you could put this enzyme literally on your skin and have it absorb in…”

Chamath:

“Game over. That alone is $2 trillion.”

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