A Calico/Revel Pharma enzyme designed via AlphaFold-guided directed evolution to break down the glycation byproduct CML was applied to donated skin from patients over 70, eliminated 55% of the CML, and reversed the skin's measured age down to that of a 31-year-old.
In the Science Corner, Friedberg describes a new Calico/Revel Pharma enzyme that clears the glycation byproduct CML from the extracellular matrix, which in a skin sample test reversed apparent skin age from over-70 to 31 years old. ✦ AI generated
David Friedberg · All-In Podcast · 2026-07-18 · original ↗
starts at this moment · 86:31
“Do you guys want to talk about reversing aging?”
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 which basically reversed the skin's age down to the age of a 31y old. This is from greater than 70 year old patients just by putting this enzyme on the skin.
verbatim transcript · starts at 86:31
86:31we would find in our body, cassine, collagen, retinal proteins which are in your eye, hemoglobin, and they were able to get rid of 52 to 97% of the CML, just degraded away. >> And then they um 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
87:02to eliminate 55% of the CML on the skin which basically reversed the skin's age down to the age of a 31y 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
87:27do 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. And now the next set of questions is okay well great this enzyme is awesome. How are we going to get it into our bodies? How are we going to get it into that extracellular matrix? Is it going to be a cream? Is it going to be a
87:44shot, a supplement? Could we eventually take an RNA shot that makes the protein inside of our body and starts to do the degradation from within? A lot of questions kind of still to be answered, but it really, I think, lights a great path forward. >> Amazing >> for these novel therapies that we're developing. It's [ __ ] awesome. I mean, dude, likeing, >> you know, all my I got all these joint
88:03pains in my hip and my shoulder now. Like everything you can feel yourself getting older. >> Well, that's I I will tell you this right now. That will not be the first market. The first market will be cosmetic and >> cosmetic skin. Yeah. >> It will be a trillion dollar market. If if you can create a cream, >> dude, if you could put this enzyme literally on your skin and have it
88:21absorb >> a cream. >> Yeah. >> Game over. It's it's a that that alone is $2 trillion. >> But I mean, dude, AI, let's just talk about applications of AI, why it's actually awesome that everyone should be able to agree on and you can't be convinced by some foreign scop. This is [ __ ] awesome. I mean, this was alpha full used to discover this thing and
- ·Calico/Revel Pharma enzyme designed using AlphaFold-guided directed evolution
- ·Targets CML, a glycation byproduct in extracellular matrix
- ·Applied to donated skin from patients over 70
- ·Eliminated 55% of CML, reversed measured age to 31
- ·Directed evolution + AlphaFold enables precise enzyme design
- ·Single application produced dramatic apparent age reversal
- ·Signals new approach to targeting aging biomarkers directly