“Age Reversal Is Coming.” Everything You Need To Know - Dr David Sinclair - #1141

**Chris Williamson** (0:00)
The first ever podcast episode that I recorded in America was with you in 2019, Harvard Medical School in your office with what looked like the illustration of a snail on the whiteboard. And it was filmed on two iPhones, one of which I'd had to borrow from a friend, and a single white USB microphone. And that was over seven years ago.

**David Sinclair** (0:23)
Yeah, I remember it well when you were 12, right?

**Chris Williamson** (0:26)
I was 12 Yeah, correct.

**David Sinclair** (0:28)
It was very clear from those days that you were going to be a big success. You were smart, driven, came prepared.
And look, this is beautiful now.

**Chris Williamson** (0:38)
Full circle. Yeah, I didn't realize Starbucks venti has way more caffeine in than the British equivalent, and it took my fucking face off. I was obviously trying to think about Yamanaka factors and how important NAD and resveratrol in yogurt is. Meanwhile, my whole body was vibrating. But you've done maybe more than almost anyone to make the biology of reversing aging a part of mainstream conversation. So I want to talk about everything that's happened since we first sat down, the Yamanaka factors, what's happening with NAD and resveratrol, new discoveries.
Before we get into that though, what discoveries have excited you most since 2019?

**David Sinclair** (1:23)
Gee, a lot. I'm very lucky to have a lab where there's up to 40 people running around making discoveries. I go back there to recharge. It's like the Willy Wonka. You've been there, so you know what it's like. It's unparalleled. I wish everyone could come visit.
The highlights would be, so in 2020, we published on the cover of Nature magazine that we could reverse aging safely in an animal for the first time, a mouse. We cured its blindness. That was pretty big. Cover of Nature, it's what most scientists dream of in their lifetime. That was pretty big high.
Since then, it's been rewarding to see that it's been repeated not just by other labs but in different animals, monkeys. It's been working in different tissues, so it's not just the eye anymore where we first tested it. It's pretty much working in every part of the animal's body. And then the big thing is we've now gone into people. So there are people getting hopefully their age reversed in their eye to cure their blindness or at least improve their vision at the very least.

**Chris Williamson** (2:31)
Why start in the eye?

**David Sinclair** (2:33)
Yeah, good question. This is a gene therapy. So we're introducing genes that are very powerful. They're called Yamanaka factors, you mentioned them. But we use a subset of them that don't cause any trouble. If you just use what Professor Yamanaka used, it's not going to be very healthy. It's actually quite dangerous. So we use a subset of those and we deliver them with a little virus-like particle.
The safest way to deliver a virus-like particle into a human is to go into a space that's enclosed, it's not going to spread, and the eye is where it's most being tested.
We did it for safety reasons, not because it would work better in the eye. In fact, I told my student at the time, Wan Cheng, that he was crazy to try to cure blindness. Why not do something easier like the liver? But he said, the eye is probably the best place to start for safety reasons, and he was right.

**Chris Williamson** (3:25)
I remember that though. We were talking about that in 2019 when I was in your lab.
There's been this recent release that came out last month. What's that? Why is that so special?

**David Sinclair** (3:41)
The one about that we've gone into humans?
Well, I think most people thought the aging field was a lot further behind. Age reversal you see online, oh, we've done this in human cells. We've done it in a mouse, but suddenly there are people now getting what could be the world's first true age reversal drug.
For us, it was old news. We'd been doing this and expecting it for a while. In fact, we made the discovery back in 2016-17. For us, it wasn't so amazing. But for the world, I think it was a shock to hear that people are actually getting this potentially age reversal drug for the first time.

**Chris Williamson** (4:19)
What would be the issue that somebody has in their eye which would be reversed? What's the sort of patient that this would fix?

**David Sinclair** (4:25)
This is the thing that makes me super excited, is that every type of damage and disease that's been tested in animals, not just mice but larger animals, it's worked to improve the vision of either a disease or damage. So for instance, if you pinch the nerve, you laser it or you give a mouse glaucoma pressure in the eye, we can treat that effectively. Nothing reverses blindness currently except for this treatment in animals even. So that's what's exciting. Even macular degeneration, glaucoma, the two leading causes of blindness in the world, both of them are really easily treated by this new mechanism. We call the drug ER100, which is epigenetic reversal 100