Inside the World’s First Age Reversal Trial | Lifespan with Dr. David Sinclair - S2, Ep. 4

Summary

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Lifespan with Dr. David Sinclair

S2, Ep. 4 — Inside the World’s First Age Reversal Trial

Release Date: July 23, 2026

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Episode Overview

In this illuminating episode, Dr. David Sinclair and co-host Matthew LaPlante explore the science and practicalities of vision and aging, anchored by an inside look at the world’s first human age reversal trial for blindness. The conversation weaves through the anatomy and biology of the eye, the latest technological and clinical advances in tracking and reversing eye aging, lifestyle strategies for preserving vision, and the astonishing possibility of brain and whole-body rejuvenation. Dr. Sinclair shares exclusive insights from his lab and the industry’s frontline, making the science accessible and actionable for everyone.

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Key Discussion Points & Insights

1. Anatomy & Biology of the Eye (08:30–16:00)

• Eye Structure Primer:
  Matthew and David detail the essential parts of the eye:
  • Cornea, iris, pupil, lens: protective and light-adjusting components.
  • Retina: the "most complex" part, crucial for vision, composed of rods (low light, no color) and cones (color detection).
  • Retinal Pigment Epithelium (RPE): supports rods and cones, key for maintaining eye health.
• Fun Fact:
  Opsins—light-detecting proteins—exist in the skin and brain, not just the eye.
  • Dr. Sinclair [16:00]: “There are opsins... that do not only occur in the eye. You’ve got seemingly photoreceptors in your skin and even in your brain.”

2. Vision as an Extension of Brain Health (12:28–24:50)

• The optic nerve is an actual extension of the brain, so eye health gives a window into brain health and aging.
  • Matthew LaPlante [21:01]: "Your eyes aren't just a separate sensory organ. They are part of your brain."
• Measuring Aging via the Eye:
  • Non-invasive AI retinal scans can estimate biological age, track brain health, and predict disease risk.

3. Epigenetic Reprogramming & Age Reversal Trials (03:37–05:42, 24:41–32:04)

• ER100 Clinical Trial:
  The first FDA-cleared cellular rejuvenation therapy (ER100) for humans uses controlled expression of Yamanaka factors (OSK genes) to rejuvenate retinal cells.
  • Early results are “going well”; the first patient treated brought 30 years of research “full circle.”
• From Mice to Monkeys to Humans:
  • Techniques reversing age and vision loss in old/glaucomatous mice (2020 landmark paper) now work in monkeys with nearly human-identical eyes.
    • Dr. Sinclair [31:42]: “Now that it’s working in the monkeys... if it works in a monkey, it’d be shocking to me if it doesn’t work in humans.”

4. The Theory—Backup "Youth Software" in Cells (28:57–30:55)

• There’s a presumed “backup copy of the software of youth in every cell.”
  Reprogramming with OSK turns the cellular age back about 80%, but crucially, does not risk cancer—a natural safety barrier.
  • Dr. Sinclair [29:58]: “It’s seemingly perfectly safe in the mouse. And the effect lasts for many months after we switch it off.”

5. Universal Nature of Age Reversal (25:37–27:57)

• Proof-of-concept in the eye supports the information theory of aging throughout the body.
  Results aren’t limited to vision restoration—restoration of “youthful function” is now observable in mouse brain, kidney, muscle, and potentially the entire organism.

6. Age-Related Eye Disease Primer (15:04–16:00, 33:16–34:48)

• Macular Degeneration, Glaucoma, Cataracts:
  • AMD Types:
    • “Wet” (excess blood vessel growth) treatable with injections.
    • “Dry” (lipofuscin junk accumulation), currently untreatable.
• Rejuvenation removes cellular junk—restored youthful retinal structure, with the eye naturally clearing protein/lipid aggregates when aged cells are reset.

7. Why Everyone Should Care: The Perils of "Normal" Eye Aging (36:35–38:19)

• Inevitability & Prevalence:
  Vision problems will affect most adults—difficulty reading, glare, color changes, eventual need for glasses or surgery—yet we wrongly accept this as unchangeable.
  • Matthew LaPlante [37:29]: “If you’re an adult aged 40 to 60, you will experience symptoms of age-related vision changes. This happens to all of us.”

8. Practical Vision Preservation: What You Can Do Now (41:51–54:44)

• Key Nutrients:
  • Vitamin C: Decreases glaucoma risk, combats oxidative and UV damage ([42:16]). Dr. Sinclair recommends moderate supplementation (1g/day).
  • Vitamin A (from beta carotene), E, Zinc, B1/B-Complex: Support light-detecting proteins, reduce inflammation.
  • Omega-3 Fatty Acids: Key for reducing glaucoma risk and alleviating dry eye; fish oil, NMN, and low-dose rapamycin can help dry eye ([47:10]).
  • Lutein, Lycopene, Astaxanthin: Plant antioxidants clinically proven for retinal and macular health.
    • Dr. Sinclair [47:31]: “Lutein is great. Take that every day.”
• Diets & Lifestyle:
  • Eat “the rainbow”—fruits/veggies rich in color and phytonutrients.
  • Mediterranean, plant-based, and calorically restricted diets have proven vision/longevity benefits.
    • Dr. Sinclair [51:24]: “Caloric restriction slows aging across the entire body. The eyes, of course, are no exception.”
  • Specific foods: Dark berries, kale, carrots, peaches, tomatoes.
• Circadian Rhythm & Sleep:
  • Sirtuin-related longevity genes (needs NAD) regulate circadian rhythms, sleep, and aging; supplementing NAD precursors may help sleep and eye health.
• Violet Light:
  • Not to be confused with UV; essential for preventing myopia/vision loss. Artificial (screen) lighting often lacks this spectrum.
    • Dr. Sinclair [53:54]: “Without [violet light], you get shortsightedness… LED screens... don’t produce enough violet light.”
  • Solution: Spend more time outdoors; consider supplemental violet light sources.

9. What to Avoid (54:44–63:00)

• UV Exposure: Increases risk of cataracts, macular degeneration, and eyelid cancers; wear sunglasses and avoid excessive sun/UV.
• Smoking & Alcohol: Directly damage the retina, raise AMD risk, and globally accelerate biological aging.
  • Dr. Sinclair [61:10]: “Drinking when you’re young will accelerate the biological clock.”
• High Omega-6/rich animal fat diets: Correlate with poorer eye health over time.
• Ocular Pressure: Sleeping face down, tight goggles, or activities that increase eye pressure (like bungee jumping) can accelerate glaucoma and vision loss.
• Environmental Risks: Eye trauma, lasers, chemicals, and even repeated swimming goggle use may increase risk of glaucoma.

10. Looking Ahead: Genome, Early Detection, and Emerging Therapies (65:23–68:26)

• Genetic Screening & Individual Risk:
  • Get sequenced—identify hereditary risk for conditions like macular degeneration or retinitis pigmentosa.
• Gene Therapy Today & Tomorrow:
  • Stage 1: Gene replacement (e.g., Luxturna for RPE65 mutation).
  • Stage 2: DNA editing (e.g., CRISPR for sickle-cell).
  • Stage 3: Reprogramming/chemical reprogramming — targeting the epigenome for system-wide, disease-agnostic age reversal.

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Noteworthy Quotes & Moments

• On Vision and Aging:
  “People want to see their grandkids. Without your vision, it’s not just lonely, but... it accelerates other diseases as well.”
  — Dr. Sinclair [07:22]

• On Youth ‘Backup Software’:
  “There must be a backup copy of the software of youth in every cell… This seems to be a universal software.”
  — Dr. Sinclair [28:57]

• On Noninvasive Eye Age Scans:
  “They could very accurately, within I think three years, predict how old somebody actually was just by looking... It helped predict all causes of mortality.”
  — Dr. Sinclair [22:14]

• On Violet Light and Modern Epidemics:
  “We don’t go out into sunlight and LED screens... don’t produce enough violet light for our eyes to respond to [which increases myopia].”
  — Dr. Sinclair [54:20]

• On the Power of Lifestyle:
  “Turning on longevity genes, eating the right foods, and taking these supplements... can protect the eye long term.”
  — Dr. Sinclair [69:35]

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Timestamps & Segment Highlights

• 08:30–16:00: Eye anatomy, fun facts, and evolution.
• 20:15–24:50: The eye-brain connection, biological age, and AI-driven diagnostics.
• 24:51–32:04: Bench-to-bedside: from mouse and monkey trials to human age-reversal.
• 33:16–34:48: Age-related macular degeneration, restoring youthful retinal layers.
• 38:08–39:53: Prevalence of eye aging; shifting from reactive to preventive medicine.
• 41:51–54:44: Nutritional strategies and supplement recommendations.
• 54:44–60:30: Avoiding damage: UV, smoking, alcohol, and lifestyle hazards.
• 63:43–65:15: Odd science: microgravity and “younger” eyes in mice returned from space.
• 65:23–69:04: Current and future gene/epigenetic therapies; whole-body age reversal.
• 69:35–End: Take-home messages; start now—eye aging is preventable and improvable at any age.

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Take-home Messages

• Vision loss is neither inevitable nor untreatable—revolutionary therapies are on the horizon, with the first human trials underway.
• Lifestyle choices—diet, specific nutrients, sleep, light exposure, and abstaining from smoking/drinking—have significant, measurable effects on eye health and biological age.
• Monitoring eye health is a powerful proxy for brain and overall health; new technologies allow for early detection and intervention.
• Practicing prevention now can safeguard vision for decades, and soon, advances from Sinclair’s lab and beyond may offer the prospect of biological age reversal for eyes—and the entire body.

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For deeper details, journal references, and transcript links, see episode show notes on Lifespan.com.

Transcript

[Dr. David Sinclair]

I mean, curing blindness is no small thing.

[Matthew LaPlante]

Your eyes aren't just a separate sensory organ, they are part of your brain.

[Dr. David Sinclair]

But people ask the question, well, gosh, if you're reversing aging in cells, won't they just turn into cancers? We believe and have shown that there must be a backup copy of the software of youth in every cell that we've looked at. And why not talk about it, let the world know what's happening. So reversal of aging isn't just for the eye, so seems to work across the entire body of animals too.

[Podcast Host / Narrator]

Welcome to Lifespan, a show where we discuss the cutting edge science of aging and how to live healthier at any stage of life. I'm David Sinclair, a scientist and professor working on understanding why we age and discovering new ways to slow and even

[Dr. David Sinclair]

reverse the aging process.

[Podcast Host / Narrator]

On this show, I share an insider's look at the latest from my lab, the field, and what's just around the corner. Hey everyone, welcome back. Before we dive into today's episode on Eyes and Vision, I wanted to share some important background. If you saw episode one or have been following the news, you probably know that the world of vision science is

[Dr. David Sinclair]

moving really fast right now and there's

[Podcast Host / Narrator]

been some exciting developments recently. First, you're going to hear a familiar voice. Today I'm excited to welcome back my co host from season one, Matthew LaPlante. Matt is a professor of journalism at Utah State University and recently earned a PhD in climate science as well. He's also, as you probably know, my co author on our book Lifespan. It's great to have him back. Now today's conversation focuses on the eye. Matt and I break down the science

[Dr. David Sinclair]

of vision, how the retina and optic

[Podcast Host / Narrator]

nose function and how problems like glaucoma, cataracts and age related macular degeneration develop. Importantly, we also look at the daily choices, lifestyle habits and preventative strategies you can use right now to protect your site in the long run. This episode is actually for everyone. Many of us will experience vision problems sooner or later. I can speak as a 57 year old. For some people, it starts in childhood with nearsightedness. For others, and most of us, it begins around the age of 40 when reading starts to get harder, screens get blurrier, or night driving becomes more difficult. Wherever you are on that path, this episode is for you. When Matt and I first sat down to map out the foundational biology of vision for this particular episode, we knew the field was on the verge of something really historic. And those exact theories have now crossed the line into reality. I recently co authored a review on oculomics and AI looking at how artificial intelligence can now scan the microarchitecture of the back of the eye. We aren't just talking about checking your prescription here. By using advanced AI to read subtle hidden patterns in your retina, we're getting closer to a future where a simple non invasive eye scan cannot just tell you about your vision and but also can estimate your true biological age, track your brain health, and even predict your risk for future diseases. It's wild stuff and I've put the paper in the show notes if you want to check it out. The second massive development, of course, is on epigenetic reprogramming. If you remember episode one of this season, I talked about Life Biosciences and the cellular rejuvenation technology that originally spun

[Dr. David Sinclair]

out of my lab.

[Podcast Host / Narrator]

If aging is in part a loss of biological information, then restoring that information could help cells remember how to function like they're young again. This is the idea behind ER100, the first cellular rejuvenation therapy using epigenetic reprogramming to receive FDA clearance to enter human clinical trials. ER100 or Epigenetic Reprogramming100 uses controlled expression of of OSK3 of the Yamanaka genes to try and help damaged retinal nerve cells to recover more youthful function. The Life Biosciences trial is testing the safety and tolerability of ER100 in people with blindness caused either by glaucoma, which is due to eye pressure, and by Nion n a I o n which is basically a stroke in the back of the eye. Earlier this year, the first participant actually received their first dose of ER100 and it was a special moment that I witnessed firsthand. It was really emotional after 30 years of research to finally see it entering human trials. And I'm happy to report that the trial is going well and I'll continue to report how the trial is going. So remember to hit that subscribe button and also join us as a [e-mail] to receive updates. To see a concept that we pioneered in mice and monkeys for finally being put into human beings made me extremely proud of the work my teams and my colleagues have done over the past 25 years. I want to give a special shout out to one Cheng Lu or Ryan, and to Xiao Chan, both who pioneered the work in my lab. And also I want to mention Dr. Sharon Rosenzweig Glipson, who's running the ER100 trial at Life Biosciences if you want the breakdown on OSK and how reprogramming works, definitely go back and listen to episode one of this season. Today's episode is about what matters right now in your day to day life. Understanding how your eyes age, how to catch problems before they cause permanent damage, and how to have the best chance of slowing age related decline in vision for decades.

[Dr. David Sinclair]

And with that, let's go.

[Matthew LaPlante]

Welcome to the Lifespan podcast. I'm Matthew LaPlante, this is my good friend, Dr. David Sinclair. Hey David.

[Dr. David Sinclair]

Hey, Matt.

[Matthew LaPlante]

David is a geneticist and a professor at the Paul F. Glenn center for Biolog of Aging Research at Harvard University. How are things going over there?

[Dr. David Sinclair]

Good. How are you? Matt, my lovely co host. Yeah.

[Matthew LaPlante]

How are things going in the lab? They're great.

[Dr. David Sinclair]

I have this amazing job where I get to go in and kids, as I call them, my students, usually have something really exciting to present every time I go in, it's real joy.

[Matthew LaPlante]

Do you have this thing, this has happened to me recently where when I started as a professor, I would never have called my students kids. Cause I was closer in age to them. And now as I've gotten older, now they could actually be my kids. And I do it all the time and then I apologize and they're like, it's okay, it's okay. But.

[Dr. David Sinclair]

Well, I think they don't mind because I'm now ancient and that they really are kids. They could be my kids, literally. But when I started my lab, the first person I hired was older than me, so that would have sounded weird if I called him a kid.

[Matthew LaPlante]

Yeah. We're talking today about one of the first signs of aging for many people and one of the most disconcerting.

[Dr. David Sinclair]

And that would be the eye. So the eye is one of those parts of the body that definitely will get a disease. It will be dysfunctional. At least we all experience that. It starts even in our 30s. By the time we're in our 50s, about half of us have issues.

[Matthew LaPlante]

And this is so prevalent that, and you were telling me this the other day, that when you ask people what symptom of aging they would want to reverse first, the overwhelming answer is they

[Dr. David Sinclair]

want their vision back. Because I mean, people want to see their grandkids without your vision. It's not just lonely, but it actually accelerates other diseases as well. Fortunately, you and I have our vision. But imagine, let's close our eyes for just a week and see how that would be. I think we'd be praying to see again too.

[Matthew LaPlante]

I couldn't do it. For an hour.

[Dr. David Sinclair]

Yeah.

[Matthew LaPlante]

So I'm here for this. I'm here for this conversation. I've had good eyesight most of my life. I do wear cheaters now, especially if I'm going to be staring at a computer screen for a long time in a dark room like we do when we're recording this podcast. But I think I've been maybe like a 2015 or maybe even a 2010 eyesight person for most of my life. And then this past year. Holy moly, man. It's like I fell off a cliff. Everything is harder to focus on.

[Dr. David Sinclair]

Well, that's aging. Aging is like falling off a cliff. It all happens at once. And you're getting old now, right? You're.

[Matthew LaPlante]

I am in my 40s.

[Dr. David Sinclair]

Yeah. That's when it happens. Happened to me, too, though. I've been living a lifestyle. And I know you've now adopted a much healthier lifestyle. Congrats on that. You're looking great. These lifestyle changes, which we're going to talk about this episode delay and even can reverse the effects of aging in the eye.

[Matthew LaPlante]

So in order to have this conversation, we should do a little anatomy. Right. Think of the eye as one thing, but there's a bunch of parts to it. We're probably going to use some of these terms, so can we just, like, go through these really quick?

[Dr. David Sinclair]

Yeah, I think a lot of people will remember some of these things. So the outside part is called a cornea. These are epithelial cells that protect the eye. Basically, if you touch your eye, you're damaging your cornea. My brother's had two new ones actually, in his life. He's got dead people's corneas replaced on his eyes.

[Matthew LaPlante]

Oh, fun.

[Dr. David Sinclair]

Because he had a genetic disease. That's probably for a different topic. The iris, you'll remember, is the colored part of the eye. The pupil is actually just that little dot, the absence of tissue that lets the light in. The lens is that transparent, flexible, literally a lens that becomes opaque. As we get older, we'll talk about aging. Of all those components, one of the most important and actually the most complex part of the eye by far is the retina, which is the place at the back of the eye, this curved receptor region with the rods and the cones. Actually, there's a lot of molecular biology, which we'll get into later that's interesting, about what allows us to see in different colors and why some species are much better than us at seeing and what goes wrong as we get older to the retina. But it's super Interesting, because in my lab, we now study the retina because it's a really interesting place to reverse aging and get vision back. But it's got multiple layers, and it starts with nerves, and there's blood vessels, and then there's the rods, the cones, and some what are called rpe, retinal pigment epithelial cells behind that that support those rods and cones.

[Matthew LaPlante]

Can we do the difference between rods and cones?

[Podcast Host / Narrator]

Oh, yeah.

[Dr. David Sinclair]

So the rods don't help with color vision. They're the ones that are very sensitive to low light, basically black and white ones. Rhodopsin is the chemical in there that detects those very small amounts of photons. And then the cones are the ones that have the red, green, or blue detection. And they have different proteins in there that detect those different wavelengths. Those nine proteins called opsins, and they detect different wavelengths. And some species have a lot more. Actually, we only detect three colors. And there are some species that detect a lot more.

[Matthew LaPlante]

Like the mantis shrimp. That's my favorite one.

[Dr. David Sinclair]

I have a mantis shrimp, actually.

[Matthew LaPlante]

You were telling me this. You had one, and it makes the little noise. Right.

[Dr. David Sinclair]

It cavitates the water and makes a massive sound. Uses it to stun its prey. But its eyes, what's interesting is I think they got 16 different color detection in the ultraviolet and infrared spectrum. So we're fairly blind compared to a mantis shrimp.

[Matthew LaPlante]

It's weird to think about that there's all of these other things that are out there that we could see, but for the fact that we have these really limited eyes compared to so many other creatures out there.

[Podcast Host / Narrator]

Yeah.

[Dr. David Sinclair]

Even insects, which we often look down on, they see often in four colors. They see ultraviolet as well. And I think many of us have seen those pictures of what an insect sees. And the flowers are so much more beautiful when you have an insect's vision.

[Matthew LaPlante]

But on the other hand, we do better than dogs, right?

[Podcast Host / Narrator]

Yeah. I mean, poor dogs.

[Dr. David Sinclair]

They've evolved to be able to see their prey. They can see things at distances. They detect movement very, very well, much better than us. But they really only can see in the blue and the yellow. And so they're kind of red, green, colorblind.

[Matthew LaPlante]

On the other hand, they have all of these other senses that we really haven't developed as well. Like their sense of smell is profoundly

[Dr. David Sinclair]

better than ours or thousands of times more. Yeah. So they're not lacking.

[Matthew LaPlante]

They're okay. The dogs are always happy. You look at them, they're always happy.

[Dr. David Sinclair]

That is true. You also don't miss what you don't have. And so I'm sure they don't miss seeing the color red.

[Matthew LaPlante]

Okay, we don't miss what we don't have. But you and I have had this discussion before. If you could see uv, you would. If you could genetically modify yourself.

[Dr. David Sinclair]

Absolutely. If I could enhance myself easily, I would.

[Matthew LaPlante]

Is that one of the first things you would do if you could hack that way?

[Dr. David Sinclair]

I'd like to try it. You just would take an opsin from, say, a spider or one of these mantis shrimps, and you could use gene therapy and just stick that into the back of your eye. I recall somebody did this in a mouse, and the mouse could now see in the ultraviolet spectrum.

[Matthew LaPlante]

Dude, is that mouse freaking out?

[Dr. David Sinclair]

No, I think they're probably just saying, cool, man.

[Matthew LaPlante]

A couple other things we need to go through here. The optic nerve.

[Podcast Host / Narrator]

Yeah. These are the bundles at the back of the eyes, the retinal ganglion cells, which project out the back of these rods and cones and gather into a large cord that comes out the back of the eye. It's about a centimeter to the back of the brain. It's actually an extension of the brain. So, literally, your eye is a piece of your brain. And that's why, as we'll talk about later, the eye can be used as a bellwether for the health of your own brain.

[Dr. David Sinclair]

Next is the vitreous humor.

[Matthew LaPlante]

The vitreous humor? Yeah. It sounds like a type of standup comedian. Like, he's got a real sense of vitreous humor.

[Dr. David Sinclair]

Well, as you know, it's the liquid inside the eye.

[Matthew LaPlante]

I like the way that you say as. I know. Like, I actually. I have no idea. I had no idea until we were preparing for this show what the vitreous humor was.

[Dr. David Sinclair]

What did you think? The eye was filled with a clear,

[Matthew LaPlante]

gel like, substance that had no humor. It was very serious.

[Podcast Host / Narrator]

Yeah, well, actually. So this substance, the problem with it,

[Dr. David Sinclair]

with aging, is that it doesn't drain

[Podcast Host / Narrator]

well, and so the eye can swell up. This is the disease called glaucoma. It's very serious and affects millions of people just here in the US and that's one of the things we're working on in my lab, is curing blindness caused by that high intraocular pressure.

[Dr. David Sinclair]

Hey, there's the sclera. You know the sclera, Matt, that is

[Matthew LaPlante]

the white, opaque outer layer of the eye.

[Dr. David Sinclair]

It is. Do you know why it's white?

[Matthew LaPlante]

I do not, no. But you promised to tell me.

[Dr. David Sinclair]

Well, the current theory is that it helps humans see where the person is looking. And it's very helpful to be able to judge people's emotions. And there are number of species, our

[Matthew LaPlante]

eyes are white so that other people can see where we're looking.

[Dr. David Sinclair]

Apparently. According to the experts who study the sclera, there are many species of mammals, at least 25, that have these whites around their pupils so that other members of the species can see where they're looking. Even gorillas and some other primates have whites around their eyes.

[Matthew LaPlante]

Wouldn't that be detrimental in some ways too, because our prey and our predators could also see where we're looking?

[Dr. David Sinclair]

Yeah, maybe it's controversial. It's not proven that that's why we have white eyes. It may be a sign of health.

[Matthew LaPlante]

Right.

[Dr. David Sinclair]

That's another thing that we like to have is to show the opposite member of our species or whatever we want to attract.

[Matthew LaPlante]

It could just be random also. Right. I mean, there are things in evolution that are just like. That's just how it worked out. There's not a real strong Darwinistic explanation.

[Podcast Host / Narrator]

It could be, but actually not all scoliae are white like bonobos have light brown sclerae. But anyway, there's some other regions of the eye we should just mention.

[Dr. David Sinclair]

There's the macula, which is the central area in the retina that is important for very detailed vision.

[Podcast Host / Narrator]

So when you look at the back

[Dr. David Sinclair]

of the eye, the optometrist or the optician, they'll look at that region and have a look.

[Matthew LaPlante]

Very, very small part of the retina.

[Dr. David Sinclair]

Super dense region where there's a lot of nerves.

[Matthew LaPlante]

And super important because we're going to be talking today about age related macular degeneration. That's the part of the eye we're talking about.

[Podcast Host / Narrator]

That's right.

[Dr. David Sinclair]

And there's a couple of types of that. What can happen is the blood vessels grow too much around that region and you can also accumulate junk.

[Matthew LaPlante]

And then even smaller than the macula is the very tiny little pit in the center of it that provides the sharpest vision. That is the fovea.

[Dr. David Sinclair]

The fovea, yeah.

[Matthew LaPlante]

Okay. All right. That's the eye.

[Dr. David Sinclair]

That is the eye.

[Matthew LaPlante]

We just went through the eye. I'm sure on the show notes, we'll put on a little diagram so that people can reference if they need you to.

[Dr. David Sinclair]

Yeah, there's a reference I want Andrew to put up on the website, which is there's a fun fact about the eye that I didn't know till I researched it.

[Matthew LaPlante]

Tell me your fun fact.

[Dr. David Sinclair]

So there are opsins. These Proteins that detect light that do not only occur in the eye.

[Matthew LaPlante]

Oh, they also occur in your.

[Dr. David Sinclair]

Everywhere. You've got seemingly photoreceptors in your skin and even in your brain. There was a paper.

[Matthew LaPlante]

Okay, I knew about the brain one. You have opsins in your skin as well. Yeah, yeah, yeah. This is why photobiomodulation works, right?

[Podcast Host / Narrator]

It helps.

[Dr. David Sinclair]

This is how we know it's daylight. Even some people who are blind know that it's daylight. Their bodies can keep a rhythm and even can detect bright light even though they can't see anything.

[Podcast Host / Narrator]

This paper, which was interesting that I found, was in Science, I believe, in 2002, and its title was Phototransduction by Retinal Ganglion Cells that set the circadian clock.

[Dr. David Sinclair]

And.

[Podcast Host / Narrator]

And these ganglion cells are not detecting light for vision, but they detect it so that other things can happen. Regulating organs, metabolism, making you hungry, setting your ability to sleep at the right time. One thing that's important to me is that Lifespan Only partners with companies that I genuinely believe in. They must be grounded in science and willing to support medical research that will ultimately change how we treat aging and diseases. Their support also helps keep this podcast free for millions of listeners around the world. One of those companies that I'd like to mention is ketoneiq. I've known the founder, Mike, for over five years, and I'm a huge fan of what he's doing. I've been studying the benefits of fasting for over 25 years now, and one of the most important molecules is beta hydroxybutyrate, or bhb, the primary ketone that our bodies make during fasting. That's an important metabolic fuel for your brain and your muscles. More recently, science has shown that BHB is also an epigenetic regulator of your immune T cells. These are cells that protect against viral infections. Ketone IQ is a little shot that contains R13 butan diol, a naturally occurring molecule that your liver converts into bhb. And it happens in minutes instead of the day or two it normally takes through fasting. One of the studies on BHB that caught my attention recently was by Stephen Kernane and colleagues. Their work in 2016 showed that while the aging brain loses its ability to

[Dr. David Sinclair]

use glucose efficiently, its ability to use

[Podcast Host / Narrator]

ketones remains largely intact. That finding has helped spark an exciting new area of research on brain metabolism. And more recently, Quinonez and Lehman published a randomized trial in 2022 in the journal Nutrients, showing that ketones help preserve reaction accuracy during prolonged, mentally demanding exercise. And another study in that same year found that patients with severe COVID 19 had impaired ketogenesis, the ability to make ketones. In their experiments, adding BHB improved both the CD4 and CD8T cell functions, suggesting that ketone bodies may help restore antiviral immune responses under those conditions. Personally, I use ketone IQ quite often when I have a long day, when I'm recording podcasts, I'm writing, or I'm feeling a little down or maybe getting a virus. I'd love you to try Q10 IQ too. I asked the guys at the company to offer a 30% off discount for your first monthly order, which they kindly agreed to. You can visit ketone.com lifespan or at the checkout, just use the code lifespan.

[Matthew LaPlante]

And this is our brain using light in other ways than to facilitate vision. But there's another way that our eyes and our brains are interconnected and need one another.

[Dr. David Sinclair]

Yeah. And you can find these in the skin and in the brain and all sorts of places. Back of the knee. So circadian rhythms are important for aging. It turns out as we get older, we don't sleep as well. A lot of people struggle to even go to sleep and stay asleep. And one of the main reasons is the circadian rhythm is controlled by longevity genes, the sirtuins and the SIRT one Sirtuin that needs NAD struggles to work in the elderly because we don't make enough NAD as we get older. And one of the things we're working on is whether we can replace the NAD or enhance it and get people to wake up nice and early, nice and chirpy, and then sleep well at night. And so far, it looks good in mice. And we're doing clinical trials now in people.

[Matthew LaPlante]

So let's go back to this idea that we shared earlier, which is that everybody is going to experience some loss of vision, some loss of function of their eyes as they age. When this starts to happen, it's pretty disconcerting. And I think it's especially disconcerting when you realize something about your eyes that maybe a lot of people don't realize or fully recognize, which you mentioned earlier. Your eyes aren't just a separate sensory organ. They are part of your brain. Yeah, the exposed part.

[Dr. David Sinclair]

When I'm looking at you in your eyes or if you're staring at your partner in their eyes and you think, oh, it's a window to their soul, quite literally, you're looking straight into a part of their brain at their extensions. So when you look at.

[Matthew LaPlante]

If you're like, I really like you for your brain or I like you for your eyes? I don't know.

[Dr. David Sinclair]

Same thing.

[Matthew LaPlante]

Yeah. This is key because as we've noted on this podcast before, we know that different physiological systems experience aging at different rates. Our heart experiences aging different than our liver, different than our skin, different than our eyes. And we can measure a lot of these systems without too much trouble. But the brain thankfully is very well protected and so it's a little harder to non invasively measure aging in the brain. But our eyes are exposed to the world, so we can measure aging in the eyes.

[Dr. David Sinclair]

Yeah, there have been a number of studies that use different aspects of the eye to measure how fast people are aging. There's one where you pull liquid out of the eye, this humor, and look at the proteins and they could quite accurately develop a clock that's a syringe

[Matthew LaPlante]

or like a swab.

[Dr. David Sinclair]

I'd say it's small syringe.

[Matthew LaPlante]

I don't think I want to do that one.

[Dr. David Sinclair]

No, that one's probably not for mainstream. And there's actually another one that's even less for mainstream where they actually take your eyeball out. You have to be dead there. They could look at the eyes and determine the age of the person pretty accurately.

[Matthew LaPlante]

But that doesn't do you a lot of good because you're already dead. So we don't like the syringe one, we don't like the dead one. There's another one though, that is really interesting.

[Dr. David Sinclair]

Well, it's this study where they talked about 80,000 images of the back of the eye. This is data with the UK Biobank. And they could use AI to look at the differences over time as to what happens. And they could very accurately, within I think three years, predict how old somebody actually was just by looking.

[Matthew LaPlante]

And that's about as non invasive as it gets. Right. It's just a photograph.

[Dr. David Sinclair]

Yeah, it's a great measure. I think in the future doctors should be using that and maybe there will be machines for that. The other thing that was interesting is that it helped predict all causes of mortality. And so you could say, well, this person, even though they're, let's say 50, their eyes are more like 60. And that predisposed them to diseases that would eventually kill them.

[Matthew LaPlante]

Yeah, this is really important because knowing how old the eye is an important measure of overall health. There's another team of researchers from Australia that demonstrated in 2022 that the biological age of the cells in our retinas are also a predictor of mortality. That's called the Retinal age gap, which is the difference between the actual biological health of an eye and then the person's chronological age since birth. This number is interesting. A 2% increase in the risk of death from any cause for each year of difference between a person's actual age and the older biological age identified by. By the eye. So if your eye is six years older than the rest of your body, that translates into a 12% increase in risk of death. As we're talking about the aging of the eye, I should note that there have been studies in the past demonstrating a strong association between, say, like, retinal cell thickness and biomarkers for Alzheimer's disease. That's work out of a team from Seoul National University in 2021. And other researchers have observed that the eye and the brain share common mechanisms of aging and disease. And what I'm getting to here is that you're pretty sure that there's a pretty strong connection between how our eyes experience aging and how our brains experience aging.

[Dr. David Sinclair]

Well, for sure, the same structures exist. And the same process of aging occurs in the eye and the brain. The information theory of aging is now showing that, interestingly, people have, even before they knew this theory, they were looking at correlations between retinal diseases and, say, Alzheimer's disease or mild cognitive impairments. And it was shown, actually just recently, in the last couple of years, that by looking at the changes that are happening to the retina, you can predict Alzheimer's way before you have any symptoms.

[Matthew LaPlante]

And is this why it's been so important in the Sinclair lab to examine the eye? Or is it just that the eye was a convenient mechanism to examine aging?

[Dr. David Sinclair]

We chose the eye because the student at the time, Wan Cheng Luke, was excited about the eye. And I wanted to do the liver. Cause I figured that would be easy. But he thought the eye was the place to go. And he was smart about it because he realized that if it worked, we could more easily go into human studies with the eye than the liver. Because we're giving genes that are delivered with a domesticated virus called an aav. And in the eye, there's already a drug on the market using an AAV to correct a genetic defect for retinitis pigmentosa, or genetic disease.

[Matthew LaPlante]

Yeah, we're gonna talk about that a little bit toward the end of this episode. But because that was already available, what he observed, that if we are able to show that reprogramming works in the eye, there's already a mechanism to deliver whatever that is. Yeah.

[Dr. David Sinclair]

Yeah, I guess it's not obvious to everybody, but to us, we go on the assumption that if we figure out why eyes age at a fundamental level, it'll be true for every other cell type in the body. And so far, it looks like that's the case. We're now reversing the age of the brain in mice using the same technologies that we reverse blindness in mice a few years ago.

[Matthew LaPlante]

And when we talk about reversing blindness in mice, this paper that came out in 2020 that showed that genetic reprogramming using three of the four Yamanaka factors could recover youthful epigenetic information and restore vision in mice. That was a really seminal paper for your lab.

[Dr. David Sinclair]

It was a really nice milestone, and I was very proud of the team. And we wrote about it in our book Lifespan, before it even was published. It took a long time to publish it because peer review takes a while, especially with something this radically new. But it came out in. When was it? December 2020. And ever since then, we've been pushing forward pretty hard. We've made a lot of progress on this work. Originally, we quote, unquote, just showed that we could improve vision in old mice and mice with glaucoma and even mice that had damaged optic nerves. There were big questions left, like, is it really safe in the long term? How long does the effect last? Can you do it more than once? And these are questions we're now getting answers to.

[Matthew LaPlante]

And in fact, a paper called Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma adds a lot to that equation. Just what you're talking about here. That study followed many of the same steps as the 2020 paper, but the key word in that title is sustained.

[Dr. David Sinclair]

Right. It was a lot of work. I want to thank my colleague Bruce Cassandra, and Wan Cheng is also one of the key people there. And what we showed in this paper was that turning on this therapy for a long time had no negative side effects. In the 2020 paper, we found that it worked well for six to eight weeks. Great. But we didn't know which was cool. That's great. I mean, curing blindness is no small thing. We were pretty excited. But people ask the question, well, gosh, if you're reversing aging in cells, won't they just turn into cancers? Won't you just get a big tumor in the eye? And the answer to that in this paper is no. It's seemingly perfectly safe in the mouse. And the effect lasts for many months after we switch it off.

[Matthew LaPlante]

11 months.

[Dr. David Sinclair]

For 11 months. Yeah.

[Matthew LaPlante]

Which might not sound a lot, except for a lab mouse lives two to three years. So we're talking about a single, essentially a third of the animal's life. That translates into decades in human equivalence.

[Dr. David Sinclair]

Yeah, well, we're excited because most drugs stop working once you stop taking them. But this one, it's a true reset. It's a semi permanent reset. And of course, aging is still happening so that the eyes start aging out again just as it would have. But the good news is that we have an inducible system. What that means is we can turn the treatment back on again whenever we want just by giving them an antibiotic. We engineered it that way. What I think will happen is that if it all goes well, and hopefully we'll know in a couple of years or less, patients will get their vision back, glaucoma or just old age or macular degeneration patients, and it'll last for a number of years. And then they'll just take a course of antibiotics to regain their vision again

[Matthew LaPlante]

and they'll turn it back on as

[Dr. David Sinclair]

they need to keep cycling.

[Matthew LaPlante]

And that is an important part of this study, is that it showed that it didn't just stop the aging or send it on a reverse course into eternity. It reversed the aging and then reset it per the information theory of aging. And then it continued anew.

[Dr. David Sinclair]

Right.

[Podcast Host / Narrator]

Well, that's the other thing that's not

[Dr. David Sinclair]

obvious to most people who just hear about this theory. First of all, we believe and have shown that there must be a backup copy of the software of youth in every cell that we've looked at. And we've looked at a lot of different types of cells. We've now rejuvenated the kidneys and the muscle, the brain, of course, other labs have done the spleen and other tissues. So this seems to be a universal software that is in cells. Now, we don't know where that software is encoded. We think it's probably attached to the DNA somewhere, some chemical we're looking for.

[Matthew LaPlante]

Yeah, you've been really cagey about this in our last couple of conversations.

[Dr. David Sinclair]

We have some clues, but my student Chris would kill me if I divulge what happened.

[Matthew LaPlante]

If you told people where to find it?

[Dr. David Sinclair]

Yeah, stay tuned. I mean, we'll divulge it here.

[Matthew LaPlante]

There's a treasure map there somewhere.

[Dr. David Sinclair]

Exactly. There is. And we think that information is laid down when our eyes are very young, and it stays there until we trigger it to be reset. The other thing that's interesting is that now we know that it gets reset, but your Age doesn't go back to zero, which would be cancer. What happens is that this program, which is set in motion by these three genes you mentioned, which we call Os and K, these three Yamanaka factors. Age goes back about 80%, but stops. There's a barrier to the cells getting too young, which we don't understand, but we're sure happy it exists.

[Matthew LaPlante]

We don't understand, but thank God it exists, right? Because otherwise all this is for naught.

[Dr. David Sinclair]

Well, we'd have to be very, very careful with the technology. We'd have to turn it on for just the right time and turn it off again to be safe. But now we know it's not that dangerous. You can leave it on for whatever it is, third to half the lifespan. The eye just stays healthy.

[Matthew LaPlante]

You've been increasingly willing to talk about what's actually actively happening in your lab, save for the treasure map that you won't tell anybody about.

[Dr. David Sinclair]

Yeah, well, I've always talked about research early because I believe that, first of all, the public has a right to know because they're paying for a lot of this research. And also, you know, unless I'm told by my student, please don't tell anyone, because it's really competitive and I'll get scooped.

[Podcast Host / Narrator]

You know, if I feel like that's

[Dr. David Sinclair]

not an issue and we're way ahead, then why not talk about it? Let the world know what's happening. Inspired young kids to start science, inspire other labs to work on this.

[Matthew LaPlante]

You mentioned Bruce Cassandra earlier. He's a frequent collaborator of yours. He's also the co director of the Ocular Oncology center of Excellence at Harvard Medical School, and he is leading a study that helps bridge the gap between mice and men. It was described in an abstract presentation at the annual conference of the association for Research and Vision and Ophthalmology, which was held in New Orleans in April of 2023. And that was the first time that it was publicly revealed that the process that was used to restore vision in mice was also working in monkeys. Right.

[Dr. David Sinclair]

Well, that was a big deal because mouse eyes are structurally slightly different than us. They have a membrane.

[Matthew LaPlante]

They don't have the white.

[Dr. David Sinclair]

They also don't have the white. But monkey eyes are identical to our eyes. If it works in a monkey, it'd be shocking to me if it doesn't work in humans. Now that it's working in the monkeys. And those mice that had bad vision, they had their vision returned again after just 28 days of treatment. And now with Bruce, we're doing some more Studies to see how long we can leave it. If it gets better the longer we leave it.

[Matthew LaPlante]

So we're talking about African green monkeys here. How do we know that their eyesight is getting better? Because I know, like, some apes can do some sign language stuff, but I don't think African green monkeys can. They can't communicate with us. So how's that work?

[Dr. David Sinclair]

Yeah, well, we did the same thing that we did in the mice. We did two things in the mice. We exposed them, we showed them a screen, and they moved their head when the lines were moving.

[Matthew LaPlante]

We didn't do following something.

[Podcast Host / Narrator]

They follow them.

[Dr. David Sinclair]

It's called the optomotor response.

[Matthew LaPlante]

Which they weren't doing when they're. When they had their damaged eyes.

[Dr. David Sinclair]

Yeah. Or just old mice. They didn't turn their heads. And when I give talks, I show these videos of the mice turning their heads when they get their vision restored. We didn't do that with the monkeys because it just wasn't worth setting up. But what we did do that was fairly easy was to do the other test, which is called a perg, which is like ECG that we do on our hearts. We could do it on the eye. So the perg measures the electrical activity in the optic nerve and you can measure it in response to changing patterns. The P stands for pattern. And you show the monkeys in this case like a checkerboard, like a chessboard. And you can measure the changes when you show that light and the electrical activity was restored by the treatment just in 28 days.

[Matthew LaPlante]

Wow. David, we mentioned earlier that we'd be talking about the macula. That again is this little tiny part in the back of the eye that's like really important to acute vision. And that's where age related macular degeneration happens. Which has also been a subject that you and your collaborators in your lab are really, really interested in working on.

[Podcast Host / Narrator]

That's right. So this is a big disease, and

[Dr. David Sinclair]

it's increasing all the time. And there are a couple of types of amd. One is the blood vessels grow, and you can treat that with an injection that stops blood vessel growth. There's another one that's untreatable at this point, and we'll talk about ways to slow it down. And that is you accumulate lipofuscan clumps that block the ability of the nerves to work. And these are protein aggregates that have collections of damaged proteins and oxidized lipids. They're disgusting little chunks. And you can see them in the layers behind the.

[Matthew LaPlante]

I'm sorry, I'm trying not to make you laugh, but, like, I can tell my face is getting, like, the disgusted look on it.

[Dr. David Sinclair]

Yeah, I could see that they are disgusting. And what we were asking with again, Bruce, Cassandra, is when we reverse the age of the retina, what happens? Maybe nothing. Or maybe the nerves start working well. Or maybe if we're lucky, the eye gets rid of those disgusting blobs of protein and fat.

[Matthew LaPlante]

These junk boxes.

[Dr. David Sinclair]

Yeah. Yeah. And guess what happened?

[Matthew LaPlante]

The junk boxes went away.

[Dr. David Sinclair]

They went away. When you make the eye young again, it can cope. And it chews them up and they're gone. And now all the layers of the retina that looked all messed up and expanded and cells growing in the wrong places, it went back to being young again. Perfectly layered.

[Matthew LaPlante]

And this is a major cause of AMD aging. No junk boxes, of course.

[Podcast Host / Narrator]

Yeah.

[Dr. David Sinclair]

And people have tried to get rid of them, but they haven't been able to do that. And the problem is that they're buried within all these cells. And all you have to do is just make the cells young again and they go, oh, what's this crap? Let's get rid of it. And actually, one of the things that we do with Bruce again is we can grow those cells in the lab and we can make them get old. Now, we have ways of aging cells, and these are the retinal epithelial cells, these rpes that sit at the back of the retina. And when they're old, they get all disgusting. They don't really grow very well. We treat them with sodium iodate, which gives them a lot of oxidative stress, which is an acceleration of aging. And then we can reverse their age, and then they grow beautifully again. And the reason that's great is we want to use these cells to as a screen screening to find new ways to reverse aging. And we're now at the point where we can see them go from crappy, disgusting to nice and beautiful young again. And we think we can find elixirs or little chemicals that can reverse aging using those cells. And then we'll put them into the eye and then eventually into the whole mouse and then eventually into a whole human for age reversal.

[Matthew LaPlante]

A lot of people might think, okay, well, this is all nice. Sure, it's going to be nice to have this sort of intervention available if I ever get a disease that results in this sort of destruction of my vision. But I think we need to go back to this point when we are talking about macular degeneration. There's a disease called macular degeneration at a certain state and rate of degeneration. You can be diagnosed with macular degeneration, but also literally, we are all experiencing the degeneration of our macula. Not as fast as people with the designated disease. But this is all of us. This is happening to all of us all of the time, just at a slower rate.

[Podcast Host / Narrator]

And really one of the problems with medicine is that they have a cutoff.

[Dr. David Sinclair]

Right.

[Podcast Host / Narrator]

The doctors have to say, this is

[Dr. David Sinclair]

a point where we're going to treat you versus not.

[Podcast Host / Narrator]

My view is prevent the illness before it even strikes. That's probably the best way. Diabetes is a good example of that.

[Dr. David Sinclair]

We tend to have more glucose levels in our blood as we get older, but it has to reach a certain level before it becomes a disease. But does that mean when you're 0.999% away from that number, you don't have the disease? No, of course not. You don't suddenly get a disease. It's happening throughout your whole adult life, or most of it in the latter half. And vision is the same. And that's why I was excited to treat not just glaucoma and macular degeneration and nerve damage, but actual aging in mice, because aging is also a major cause of blindness. We just accept it because we think of it as natural. But being natural and common doesn't mean that it should be acceptable.

[Matthew LaPlante]

Yeah, in fact, the American Optometric association doesn't really mince words about this. It says that if you're an adult aged 40 to 60, you will experience symptoms of age related vision changes. This happens to all of us. Not everybody's going to have the same symptoms, but pretty much everybody's going to experience one or more symptoms. That's like a need for more light or difficulty reading, problems with glare, changes in color perception, cataracts. Cataracts. Eventually we're all going to get there. By the age of 50, about 60% of the population needs glasses, contacts or surgery. And that shoots up to 94% by the age of 75.

[Dr. David Sinclair]

Did you know that by 2050 it's estimated that half the world will need glasses for myopia?

[Matthew LaPlante]

Yeah, and think about that. That's half the world. Right? But that's not just half the old people, that's half the global population.

[Dr. David Sinclair]

I think already it's half over 50 now. It's gone up sevenfold in prevalence in the last few decades. No one knows why. You know, we can guess. It's computer screens. It might even be a lack of sunlight. There's new evidence that says that violet light or the absence thereof in the eye causes the eye to become malformed and nerves don't function well.

[Matthew LaPlante]

This actually reminds me a lot about the conversation that we had a few years ago now in the pilot season, the podcast. We were talking about aging of the skin. This commonness of age related loss of visual acuity is just accepted. Everybody knows it's going to happen. You just say, okay, that's just life. And this is right up there with like the idea that we are all going to get wrinkles, which, yeah, is true, but also makes us more susceptible to other health problems as we age. And so I definitely encourage people to go back and listen to that episode because skin aging isn't just cosmetic, which is why it's smart to fight it. And the aging of the eye isn't just a thing that we need to accept. We should also fight it. So, David, let's talk about what we can do to keep our eyes healthy. Because it's gonna be a little bit of time before OSK based age reversal or some other processes ready for primetime in humans. So in the meantime, as we often say, keeping your body as young as possible for as long as possible is the way to go.

[Dr. David Sinclair]

Yeah, that's right.

[Podcast Host / Narrator]

As we've discussed, our eyes can reveal a remarkable amount about our biological health. And having accurate data about the rest of your body is just as valuable. Which brings me to a science based wearable that I'm particularly fond of partly because of its scientific foundation at Harvard, where I work, but also the founder's own research and scientific rigor. Of course, I'm talking about the whoop band, the one that I rarely take off. As a scientist, I like measuring things rather than guessing. And whoop continuously tracks my sleep, my resting heart rate, my heart rate variability, respiratory rate, daily strain and recovery, and other aspects of my health, giving me objective data about how my body is responding to to the changes that I make. On weekends, you'll usually find me on Cape Cod, in my workshop or outside on the property planting fruit trees, repairing the house, or hauling lumber in my old 1992 Ford F150 pickup. Sometimes, however, I wake up eager to get outside. But my whoop tells me a different story. My heart rate variability is lower than usual, my resting heart rate is elevated, and my recovery score is really poor. So on those days I still head out, but I pace myself. I found that listening to those signals helps me recover better and work harder over the long term. I appreciate that WHOOP is backed by great science for example, in 2022, Miller and colleagues published a study in the journal Sensors comparing six leading wearable devices against clinical grade measurements of sleep, heart rate and heart rate variability. WHOOP was among the most accurate for measuring overnight heart rate.

[Dr. David Sinclair]

Hrv.

[Podcast Host / Narrator]

These are the two biomarkers that I pay close attention to because they provide valuable insights into recovery and physiological resilience. So if you don't already use whoop, I really encourage you to give them a try. So visit join whoop.com lifespan and you can use the code lifespan to receive your free Whoop and your first month of membership.

[Dr. David Sinclair]

Actually, the things that are recommended for the eyes, most of them are procedures that you can use to keep your whole body to healthy as well.

[Matthew LaPlante]

Yeah, this is a constant theme with us. So a lot of people are like, oh my God, they're going to talk about healthy eating and exercise and all that. We are. But there's some specific things that you should know about if in particular you really want to focus on eye health and eye aging.

[Dr. David Sinclair]

There's that. Well, let's start with vitamin C. Vitamin

[Podcast Host / Narrator]

C, classic vitamin C. It's one of

[Dr. David Sinclair]

the things at the top if you want to keep your eyes nice and healthy. It's known to decrease glaucoma risk, protects the eye from oxidative damage and UV

[Matthew LaPlante]

damage, and that helps prevent cataracts as well.

[Podcast Host / Narrator]

Exactly.

[Dr. David Sinclair]

So you don't want to have blurry lenses when you get older.

[Podcast Host / Narrator]

But also we need to know that vitamin C supplements might be associated with an increased risk of age related cataracts in women.

[Matthew LaPlante]

You take extra vitamin C. I take

[Dr. David Sinclair]

a middle of the road dose. So a regular dose is what, about 75 milligrams?

[Matthew LaPlante]

Yeah.

[Dr. David Sinclair]

And the upper known safe limit for vitamin C is 2 grams a day. So I'm taking 1,000 milligrams, 1 gram a day roughly. But I'm taking it for other reasons, not just to protect my eyes. In my lab we've got some published results now that ascorbic acid, vitamin C is helpful for slowing down epigenetic aging as well. And that's a whole separate topic. But yeah, vitamin C now is a staple. I've added that to my daily regimen.

[Matthew LaPlante]

So in addition to vitamin C supplementation, we're talking about fruits, oranges, watermelon.

[Podcast Host / Narrator]

Yeah.

[Dr. David Sinclair]

Sources of vitamin C, good ones are berries, dark berries. I eat blueberries with a small amount of yogurt in the morning. That's a good source.

[Matthew LaPlante]

There's another vitamin that everybody or many people associate with better vision. That's Related to an old thing that we've all heard that beta carotene, which we get from carrots, is good for eyesight. Turns out carrots are good for eyesight because beta carotene converts into vitamin A. And vitamin A is. It's good for our eyes.

[Dr. David Sinclair]

Yeah, yeah. So we can put retinol on our skin for wrinkles. Retinol is also important because it gets converted to retinal al, not oil. And that little chemical is used by the opsins, these proteins in the rods and cones.

[Matthew LaPlante]

Those are the light detecting proteins.

[Podcast Host / Narrator]

Yeah.

[Dr. David Sinclair]

So retinal is a chemical that has this strange property that when it gets hit by a photon, it'll go from a CIS to a trans, closed to an open flat structure. And that triggers what's called a G protein coupled cascade that allows the cells to now signal to the, the optic nerve, the retinal ganglion cells, that there's a signal. But those cells, they die pretty quickly because they're really going hard at it. There's a lot of oxidative stress and they need to be recycled. And so you need vitamin A to rebuild that.

[Matthew LaPlante]

You got to keep feeding them. Essentially you do.

[Dr. David Sinclair]

And those RPE cells that are defective in macular degeneration, they actually sit next to the rods and cones to gobble up the membranes that are now defective because of all of this activity. And in some forms of macular degeneration, it's this RPE65 protein that recycles the retinal back to its closed detection form. And you got to keep this cycle going all the time to be able to see.

[Matthew LaPlante]

Let's tick off a couple of other vitamins here.

[Dr. David Sinclair]

Vitamin E. Vitamin E is good, Another antioxidant. Remember, the eyes are constantly getting hit by oxidants and they're dying, need to be recycled. So vitamin E is good. Zinc is also very important. It interacts with taurine, which is thought to extend lifespan, which we'll cover in another episode. And it also interacts with vitamin A. It helps with the plasma membranes, helps with this reaction of the rhodopsins, and it also helps the neurons signal. So it's all good. So keep the zinc levels up, not too high, but just at the right levels.

[Matthew LaPlante]

And then vitamin B1. Thiamine.

[Dr. David Sinclair]

Yeah, vitamin B1, it decreases inflammation. Healthy nerves require vitamin B1, so that a B vitamin blend is what I take, which includes B1, B6, B9, B12. These are all good, especially for people like me who don't eat much meat. So B1 for eyes. What else, Matt?

[Matthew LaPlante]

Omega 3s.

[Podcast Host / Narrator]

So Omega 3s are good for all inflammation in the body. I take mine mainly to stop cardiovascular disease, but they're also good for the eyes.

[Dr. David Sinclair]

They promote the development of retinal function.

[Podcast Host / Narrator]

And it's been shown in a study that high intraocular pressure that gives rise

[Dr. David Sinclair]

to glaucoma is improved if you take Omega 3 supplements.

[Matthew LaPlante]

Finally, in this list, although this is a big list, this is non exhaustive and we should also say if you're having trouble keeping track of all of these, show notes. Show notes. Show notes. Right, yeah.

[Dr. David Sinclair]

Oh, there's one thing before you go there. Show notes are good. And Andrew, who's here with us, I'm calling him the boy wonder these days. He will make sure that all these references there. But I want to talk about something you reminded me on. Omega 3 fatty acids in the eye. A lot of people, even when they're young, have dry eye. You know, you blink, it hurts, it's scratchy. Particularly when it's winter, the air is dry. One of the ways to treat that is taking this fish oil supplement. And another way is to take an NAD booster. It's been shown in a Japanese study. NMN can actually help dry eye. And there's a third thing that's interesting. There's a drug on the market, it's low dose rapamycin. Now, those who've listened to this podcast before know that rapamycin is a longevity drug in animals and probably in people as well. It was designed to suppress the immune system, but it also, in low doses in eye drops, can prevent dry eye.

[Matthew LaPlante]

Wow. All of these things come back around.

[Dr. David Sinclair]

Yeah.

[Podcast Host / Narrator]

What's actually happening, I think, is that

[Dr. David Sinclair]

these longevity genes, they protect the body. And just like they're protecting the liver and the kidney, they also can protect and rejuvenate the eye.

[Matthew LaPlante]

Before we get away from nutrient and we start talking about other things that we can do to protect our eyes from aging. There was one more that I wanted to mention, which is lutein.

[Dr. David Sinclair]

There's a few. There's one called lutein. There's one called lycopene. Lutein I actually take every day. It's a little red capsule. Lutein is one of those antioxidants that's been shown in clinical trials to slow down eye aging, particularly as it relates to macular degeneration. This is one that I put my father on or it suggested to him, and he started taking it, let's put it that way. So, yeah, lutein is great. Take that every day. Lycopene, I don't take, but I eat enough of these reddish vegetables and fruits. So tomatoes have a lot of lycopene in them. And so that's if you eat for amount of tomato products, tomato paste, for example, loads of lycopene. I actually have the numbers here that in one large raw Tomato, you've got 5 milligrams, which is a big, big serving. But if you eat a quarter of a cup of tomato paste, maybe put it on a pizza, 19 milligrams. So this is all good. But I did find a paper that said that lycopene, when fed at high doses during pregnancy to women, children that were born, had low birth weight. So if you're pregnant, don't take high doses of lycopene, don't eat tons of

[Matthew LaPlante]

tomatoes, but if you're an adult, it's good for your eyesight.

[Dr. David Sinclair]

Yeah, that's.

[Matthew LaPlante]

Plus tomatoes are high in vitamin C, right?

[Dr. David Sinclair]

That's true. There's another one called astaxanthine, A S T, A X, a N T H I N. And it's a carotenoid. You can find it also in trout, algae, yeast, shrimp, and it actually gives fish like trout the pink color. And that's also been found to protect the eye from oxidative stress and macular degeneration and aging itself.

[Matthew LaPlante]

Okay. A lot of people might say, oh, my God, that's a lot. Right? That's a lot of supplements which remind people the best way to get nutrients is through food, if they possibly can. A lot of times we can't get probably the doses that you're talking about through food, but that's sort of the first and primary way to bring these nutrients into your body. There are several diet types that have been shown to be holistically good for eyesight and general ocular health. And these aren't going to come as any surprise to anybody who's listening to the show either. Fruits and vegetables, but go for the colored vegetables.

[Dr. David Sinclair]

So my partner Serena says, eat the rainbow, you. And I call it xenohormesis. What doesn't kill you makes you stronger. These are plants that have been stressed and produce these chemicals, and they're full of color. Anything that's colorful, so dark green, bright orange, red, these are all good for you. And in general, they're good for the eye as well. Again, I recommended to my father to go into these kind of foods, and he also went on the lutein. He's on metformin, which has also been shown to slow down Macular degeneration.

[Podcast Host / Narrator]

And he was starting to get macular

[Dr. David Sinclair]

degeneration, AMD, as it's called. And it's now completely stopped in its tracks. It's not getting any worse. It may even be better. And he doesn't even need glasses to drive at night.

[Matthew LaPlante]

Also good diet. Keto has been shown to increase optic nerve mitochondrial biogenesis, which is important because our mitochondrial mitochondria deplenish with aging. But that apparently helps with cell survival in glaucoma in mice.

[Podcast Host / Narrator]

Yeah, it does.

[Dr. David Sinclair]

Calorie restriction has been good. And plant based diets, Mediterranean diets, are all good for slowing down the aging of the eye. There was a study I want to point out in 2012 that showed that eating a lot of greens, kale, carrots, peaches, I don't like collard greens, but they were in the study. People that ate that kind of food had much lower glaucoma risk in women, probably because they have a lot of vitamin A and vitamin C and these other xeno hermetic compounds that we talk about a lot that activate these defenses against aging.

[Matthew LaPlante]

You just brushed over caloric restriction there. But there's a lot of evidence that caloric restriction, for instance, decreases retinal ganglion cell death in mice. It delays age related cataracts and rodents. It attenuates inherent age related loss of our GCs and is neuroprotective against ischemia. There's a lot of data that suggests that caloric restriction is good for eye health. What do you think is going on there in the context of the survival circuit, the information theory of aging?

[Dr. David Sinclair]

Well, if you've listened to this podcast before or read our book, you'll know that coloric restriction slows aging across the entire body. So the eyes, of course, are no exception. And what we believe is happening is that colic restriction is turning on the cell's defense against the aging process. And a major cause of aging, we believe, is the loss of epigenetic information, the ability of cells to read the right genes at the right time and maintain their function and their identity. So what we've seen and published is that during aging, cells such as the nerve cells in the eye, they lose their ability to read the right genes to maintain their nerveness, and that that leads to dysfunction and these diseases or even just bad eyesight as we get older. What do we need to do about that? We need to put the body in a state of hormesis, tricking them into thinking that times are tough and they respond in defensive ways, turning on the sirtuin genes, we've shown that happens with caloric restriction. And now these sirtuins, they go on to the DNA, they help wrap it up and maintain that epigenetic information for much longer. And so what we're trying to do is to find ways to slow that progress down, reset the system, even though we're not there yet in humans, to reset the system. There are ways, as we're talking about now, through diet, even exercise, certain foods that you can eat, supplements that activate these defenses and slow that process.

[Matthew LaPlante]

And caloric restriction is one of those ways. But what I hear you saying is that this has a whole body effect. Our eyes are part of our body. It's sort of part and parcel.

[Dr. David Sinclair]

Yeah. Protects our brain, protects our eyes, liver, kidneys. But I want to make one thing clear. It doesn't mean you have to be hungry all the time.

[Matthew LaPlante]

Right? We've never said starve yourself.

[Dr. David Sinclair]

No, but skip breakfast or have a late lunch or even have dinner and have it early and don't eat till maybe 11 o' clock the next day. These are ways to put your body in a state of perceived adversity at least part of the day. And that has huge benefits long term.

[Matthew LaPlante]

Yeah. Feeling a little bit hungry is not a bad thing. Right.

[Dr. David Sinclair]

And actually your body gets used to it when you start out first. I will admit, if you're used to eating three meals a day, you'll feel starving. You won't be able to think it's happened to me. But what happens after a couple of weeks of this lifestyle? Your body gets used to it. So I don't get hungry in the morning now and I've skipped breakfast for many years.

[Matthew LaPlante]

We've spent a lot of time so far talking about diets and nutrients that we need in order to allow our eyes to do what our eyes are designed to do. There's something else that we need, and this comes out of the work of one of your friends, Dr. Zubata. Violet light, not to be confused with ultraviolet light, which we'll get into in a moment here, but can we talk about violet light and how important it is for our eyes?

[Dr. David Sinclair]

Yeah. So Kazuo is a friend of mine in Japan and he's made some really great discoveries. One of the best ones, probably the most important one, was just a few years ago he discovered that violet light, now this is not ultraviolet light. This is, we can actually see very dark purple light. That is essential for maintaining the shape and the activity of the eye and that without it, you get shortsightedness. Or myopia. And he thinks, and I do too, that that's responsible for this sevenfold increase in the amount of short sightedness across the planet. Because we don't go out into sunlight and LED screens like our computers don't produce enough violet light for our eyes to respond to.

[Matthew LaPlante]

So the kind of light that we're getting doesn't include this part of the spectrum. And ergo, the opsons that are evolved to receive this light and to incorporate it into our biochemistry aren't getting it.

[Podcast Host / Narrator]

That's exactly right.

[Dr. David Sinclair]

And there was a, that. First of all, he did it in mice and he could show that mice responded well to this violet light. But he also looked at children who had glasses that either blocked or let this violet light through. There was a much greater incidence in shortsightedness in the kids that didn't let violet light in. And Kazuo did a very kind thing. He sent me a little USB stick that shines violet light into the kitchen wherever you plug it in. And so these days, especially during winter when I'm not outside a lot, and let's face it, I'm barely outside ever, ever, I use this violet light in the hopes that it's going to slow down my short decidedness. And I still don't need glasses. So so far so good.

[Matthew LaPlante]

But the easy answer there is go outside and get some violet light. Right. Because that's part of the spectrum that we get from the sun.

[Dr. David Sinclair]

Yeah, just a little bit. UV is still very damaging to the skin and the eyes in high doses. But a little bit goes a long way.

[Matthew LaPlante]

Yeah, yeah. So let's talk about that now. Let's talk about the things that can damage our eyes. UV is the obvious one. This doesn't just mean don't stare at the sun, that should be obvious. But we also want to avoid UV rays, which can modify our lens proteins and cause cataracts and blurry and hazy vision. And also UV rays increase the incidence of eyelid cancers.

[Dr. David Sinclair]

Yeah, in fact, UV can cause a lot of cancers, of course, on the skin being the most prevalent one. And what's happening is that the UV radiation will actually go into the cell and damage the DNA. You know how there's four bases of DNA which we call A, C, T and G. The T's actually with some UV will link together. So two T's together in a string will become a dimer, chemically linked together. And now you're screwed because now the cell can't read the DNA and there are special enzymes that remove Those. But if they don't work well, then you can actually have a mutation. And that is really the reason that UV causes cancer.

[Matthew LaPlante]

Well, so like, UV melts the teeth together.

[Dr. David Sinclair]

Basically fuses them together. Yeah.

[Matthew LaPlante]

Wow.

[Dr. David Sinclair]

Yeah, it's pretty horrible. And I remember that when I go out and spend too long. So when you're getting sunburned, that's what's happening, is your cells detect that your DNA has been damaged and they have an inflammatory response. So your cells are trying to protect the cells, but also kill off those cells that have been damaged so much that they might cause cancer.

[Matthew LaPlante]

Okay. So that sunlight, it bears mentioning because it is in the research. Don't look at lasers. Lasers are bad for your eyesight.

[Dr. David Sinclair]

They are. It's particularly dangerous if you have pet sharks with laser beams attached. So don't get those as pets like Dr.

[Matthew LaPlante]

Evil.

[Dr. David Sinclair]

Dr. Evil. Yeah. For the young people that haven't seen Austin Powers movies.

[Matthew LaPlante]

God, there are people out there who haven't seen Austin Powers.

[Dr. David Sinclair]

No. Now we're old, dude. Oh, man.

[Podcast Host / Narrator]

One thing I've learned after decades of studying aging is, is that you simply can't consistently improve anything that you don't measure. Speaking of which, a few months ago, after a lot of travel and speaking engagements and probably too many dinners out, I realized I'd put on a few extra pounds, and I could see the graph on my Withing scale, and I needed to shed a few. My goal, however, was not to simply lose weight. I wanted to get back to my usual body composition. Had I lost muscle, was my visceral fat creeping up? What did I need to focus on? That's why I like the Withings body scan scale. It tells me much more than my weight. It measures body fat, muscle mass, visceral fat, and even includes an FDA cleared ecg. As I made a few changes to my diet and got back into my normal routine, I could actually watch my body fat come down while preserving my muscle. And that's far more useful than watching a single number on a scale. I've actually been using Withings products for well over 10 years, and lately I've become a big fan of their watches as well. They continuously track heart rate, sleep activity, temperature trends, and even blood oxygen. I wear the Withings silver scan watch Nova, which looks a lot like an expensive diving watch. And my partner, Serena wears one of the slim gold models. She loves that it looks like an elegant watch first and a health tracker second. Withings also makes one of my favorite blood pressure monitors for home use. Also a sleep analyzer. That can help identify sleep issues. And they have a smart thermometer as well. To me, that's what longevity is all about. Measuring what matters, making small improvements and letting those improvements compound over the years. Withings makes it easy to build your own health home lab. So whether you're tracking your body composition, blood pressure, sleep, heart health, or activity, you'll have the data you need to understand whether the choices you're making are actually improving your health or even harming them. If you'd like to build your own health home lab like I have, visit withings.com lifespan and use the code lifespan to receive 10% off.

[Dr. David Sinclair]

The other thing that you want to make sure is that if you get that damage, you want to take out some nad released an NAD booster because it was shown by Raj Abdur, who's one of the leading surgeons in the eye, he's at Wash U Washington University in St. Louis, that if you get damaged to the retina either by lasers or by other other stresses on the eye, raising your NAD levels really does protect the eye. And that was of a lot of interest to pilots, especially military pilots who can have lasers shone straight in their eyes by the by the enemy.

[Matthew LaPlante]

So they're like carrying around some like NAD in their pocket just in case they take the laser in the eye. They can shove that down.

[Podcast Host / Narrator]

They might be.

[Dr. David Sinclair]

If they've been reading papers, they probably do.

[Matthew LaPlante]

There's two more big ones that I want to talk about. Again, these should at this point I feel like sort of be in the category of no duh information. Smoking damages retinal cells. It increases the risk of AMD and drinking. We know that alcohol consumption increases the risk of age related macular degeneration as well.

[Dr. David Sinclair]

Yeah, smoking and drinking, especially smoking, that's the fastest way to get older and you'll look older as well. But drinking, that's also very common. I used to drink probably one or two glasses a day. I now don't drink, barely ever a few times a year. One of the reasons is that it damages tissues, including the eye and particularly the brain, which of course we now know is an extension of your eye. And so for instance, total alcohol consumption does accelerate aging. You can look at the blood, you can look at the eye, and even one episode of binge drinking, which is more than five or more drinks on the same occasion, was associated with a month and a half acceleration of biological aging. I wish I knew that in my 20s.

[Matthew LaPlante]

I was just thinking about a visit I had to the University of Illinois, which is this enormous campus of 40,000 students. And I arrived there on the last weekend of finals week. And the binge drinking that was happening before my eyes was horrific.

[Dr. David Sinclair]

Well, we think that when we're young, we're immune to everything. And it is true that if you drink a lot of alcohol when you're younger, it's less damaging than when you're older, but it's still damaging. We're always aging, even from conception. And drinking when you're young will accelerate the biological clock. So try not to binge drink. If you're going to drink, drink in moderation. And try to drink, you know, not every day, because it is known that it does damage your body, and even your brain will be smaller at the end of the day.

[Matthew LaPlante]

So two other things to talk about here. Vegetable oils and animal fats. Animal fats that contain omega 6 fatty acids, red and processed meat. Do it in moderation. But it's bad for your eyes. Right. Like, over time, that's going to contribute to age related vision loss.

[Podcast Host / Narrator]

Right.

[Dr. David Sinclair]

And so, you know, there are some people that eat a lot of meat. They love meat, and it will make you feel better. Initially, you'll get fair amount of muscle. You may even lose a lot of weight being in ketosis. Long term, though, there's no evidence that that's a healthy diet when it comes to overall health, including your eyes.

[Matthew LaPlante]

One more thing that comes up a lot, particularly in relationship to glaucoma, is ocular pressure. And there are some age related findings about this as well.

[Dr. David Sinclair]

Well, there are. I mean, glaucoma is a disease. We also know that you can change the pressure of your eye in many ways. If you go bungee jumping, even if you sleep on the pillow with face down, it can change the pressure.

[Matthew LaPlante]

Okay, so bungee jumping, because you're suddenly going from, like, really high to really low, or because when you get to the end of the bungee cord, like, your eyes pop out of your head like a cartoon.

[Dr. David Sinclair]

Yeah, the second one.

[Matthew LaPlante]

Okay.

[Dr. David Sinclair]

Yeah. And so what we want to do is reduce the amount of pressure in the eye. Sometimes it occurs naturally. This is glaucoma. But the way we live can also affect it. And there was one study out of South Korea I was looking at. It was only, admittedly only 20 people in the study, but they found that people who slept face down and on certain side could increase the pressure of the eye, which has been shown in rodents. When you increase the pressure, it actually ages the nerve cells in your eye, Consistent with the information theory of aging. And that's going to lead to eventual loss of vision. So I sleep face down. And I never thought that that might be hurting my eye, but maybe it does. So there are lots of things we can do to try to avoid getting older eyes as we get older, and things you can take, things you can do, even the way you sleep.

[Matthew LaPlante]

Okay. And then some things that we can't do. But I still think in the realm of interesting things. For instance, this is my favorite one. Mice in space flight decelerated the retinal epigenetic clock.

[Dr. David Sinclair]

Really?

[Matthew LaPlante]

Yeah. This is like they put these mice up in the International Space Station. They leave them up there for a while, they bring them down, they check the retinal epigenetic clock, and lo and behold, their eyes are younger.

[Dr. David Sinclair]

Well, that's interesting. Maybe. Do they look at the methylation clock?

[Matthew LaPlante]

Yeah. According to the study, the mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing. There's less methylation.

[Dr. David Sinclair]

I wonder why that would be.

[Matthew LaPlante]

Okay. This is not necessarily news we can use. Very few of us will ever go to space, probably. And even fewer of us will stay up there for a long enough time to like a long time period of less pressure on our eyeballs. But if you're friends with Jeff Bezos, maybe.

[Podcast Host / Narrator]

Yeah.

[Dr. David Sinclair]

But it does bring up a theme, which is protect your eyes from radiation, pressure, chemicals. The more damage you do to your eyes, the faster they will age. Even goggles, like swimming goggles.

[Matthew LaPlante]

Swimming goggles, yeah.

[Podcast Host / Narrator]

Yeah.

[Dr. David Sinclair]

That's been shown to increase the risk of glaucoma. So you want to wear the ocular pressure.

[Matthew LaPlante]

Yeah, yeah.

[Dr. David Sinclair]

It's similar to the ears. And we should do an episode on ear aging Because a lot of people have loss of hearing as they get older. It's rarely appreciated how bad it is. And one of the things that accelerates hearing loss is damage to the ears. Like a rock concert. And we think, go to rock concert, my ears will ring a bit next day, I'll be fine. Not true. Your ears will be older because of that damage. Same for the eye.

[Matthew LaPlante]

So you think we should do a show on ears as well? I'm listening.

[Dr. David Sinclair]

We're going to do one. But your jokes have to be better next time.

[Matthew LaPlante]

All of this is really important for everyone. I want to. I just really want to emphasize this. This is not just information for people who are genetically predisposed to diseases of the eyes. If you are susceptible, though, these principles are doubly important. So as we also often say on this program, it really is important to Understand your genome, get sequenced, and then consider testing for the early signs of these conditions, because if you are susceptible to them, it's even more important to do all of these things to be protective and not to do things that are damaging your eyes.

[Dr. David Sinclair]

Yeah. We live in an age where you can get your genome analyzed either for a few hundred bucks or a few thousand. You can do it at shallow or deep sequencing, and it can tell you if you have susceptibility to retinal damage, or you might get amd, macular degeneration or even retinitis pigmentosa. The good news about those diseases now, particularly retinitis pigmentosa, is that you can get a drug that cures your genetic defect. In the case of the RPE65 mutation that runs in families, Luxturna is a drug. It's actually gene therapy from Spark Therapeutics. Jean Bennett and her colleagues, I think it was just a few years ago, got permission to sell a drug that cures that genetic disease.

[Matthew LaPlante]

That's Luxturna in 2017.

[Dr. David Sinclair]

Yep. And it's the same technology, actually. We're working with Gene's advice.

[Matthew LaPlante]

With the aav.

[Dr. David Sinclair]

With the AAV to deliver the Yamanaka factors.

[Matthew LaPlante]

This is the domesticated virus, right? Yeah.

[Dr. David Sinclair]

So you inject it into the eye just once, and we've engineered our virus to turn on and off with an antibiotic doxycycline.

[Matthew LaPlante]

Well, let's explain the LXTERNA thing, because they're not delivering the OSK genes. They're delivering basically the healthy variant of the gene that people with this disease do not have.

[Dr. David Sinclair]

Right. So that's stage one gene therapy.

[Podcast Host / Narrator]

Right.

[Dr. David Sinclair]

Replace what's missing. The next stage is to knock out or change the composition of genes. Treatment for sickle cell anemia was approved by the FDA using CRISPR technology, the technology that allows us to go in and change individual bases and chemical letters on the DNA. That's stage two. Stage three will be what we're doing, which is going in and changing, actually, the behavior of the cells. And that seems to be very effective, not just in one particular disease, but across many.

[Matthew LaPlante]

Yeah. And that's really the gold standard. The gold standard is ultimately going to be reprogramming.

[Podcast Host / Narrator]

Yeah.

[Dr. David Sinclair]

And what we're doing now, which we published one paper on, is chemical reprogramming. So instead of gene therapy, which is what's going to be our first clinical trial, we hope that with just a pill, take it for a month, you'll get your eyesight back.

[Matthew LaPlante]

And that's likely because of the trajectory of the research and stuff that's come out of your lab and decisions that were made by your people in your lab, it's likely that what we're going to see is reprogramming of the eye first and then ultimately the entire body. So if you're watching the trajectory of how this is going to come into human lives, Eyes probably ahead of most other things.

[Dr. David Sinclair]

Right, right. Because eyes are a very good place to start. They're a little sack of liquid. If you were to choose a place that's safe to inject something like gene therapy, a sack of liquid is pretty good. And that's what your eye is. And that's why we started with the eye. But it doesn't mean that the same therapy won't work for the brain, for the liver, the kidney, and eventually the whole body. There's a study that showed that this age reversal technology that we co developed reverses aging in the whole body of a mouse. And now those mice that were very old when they were treated 25 months, the remaining lifespan was an additional 109%. So reversal of aging isn't just for the eye. Seems to work across the entire body of animals too.

[Matthew LaPlante]

Oh, we should keep an eye out for that.

[Dr. David Sinclair]

Oh, Matt, we should look for it.

[Matthew LaPlante]

Yeah, Yeah, I guess we'll see.

[Dr. David Sinclair]

Matt, I think that's enough. You and your puns.

[Matthew LaPlante]

Good conversation today. Thank you so much. I feel like when we started talking about this subject, you and I a few weeks ago said, hey, let's do an episode on aging of the eye. And this has happened to us a few times now. We go like, ooh, is there enough to have a conversation about? And then there's almost too much to have a conversation about.

[Dr. David Sinclair]

Yeah, I thought today was really good. We got a lot of take home messages about what people can do now, even if they're young, to make sure that they are able to see later in life. And I wish I had this information when I was young because I probably have even better eyesight now. So even if you're in your 70s, maybe in 80s, you should start now. It's never too early to start protecting your eye. Turning on longevity genes, eating the right foods, and taking these supplements that we believe can protect the eye long term.

[Podcast Host / Narrator]

It's been great to have you with us. This is a show where science and evidence come first. The team works hundreds of hours to bring you only the facts. To learn more and to join our community, visit lifespan.com and you'll get early access to future episodes to the lifespan magazine and to detailed episode show notes. You also get transcripts and links to the papers we talked about today. As a member, you'll actually be helping us support medical research to extend all of our healthy lives. If you found this episode valuable, do consider subscribing and also turn on your notifications so you don't miss new episodes. It'll also help us make a better show for you. And feel free to share this episode with any family or friends who you think might enjoy it and learn from it. Finally, for the latest discoveries in longevity science, consider following us on Instagram, ifspan and on X joinlifespan from all of us at Lifespan, thank you for being

[Dr. David Sinclair]

part of this growing community.

[Podcast Host / Narrator]

And remember, life's short, so let's change that together. Lifespan is produced by Andrew the Wonder Man Ying Rajeev Geek me out. Ramesh Marissa who's on first, volgamore, Kathleen Tldr Fitzgerald and our researchers Shivani. Just one more thing. Sethi and Adeev Meet me in the year 3000 Johnson. Also, I want to mention our new recruit, Daniel Rocketman Salazar, who's our new producer, and of course Serena my Honeypoon. I also want to thank Inspiro Studio and Create Ape for making this show possible. And finally, thanks to our partners for helping us support longevity research.

[Dr. David Sinclair]

We'll see you next time.

[Podcast Host / Narrator]

This show is for informational purposes only

[Dr. David Sinclair]

and is not medical advice.

[Podcast Host / Narrator]

Please consult a qualified healthcare provider as individual results may vary. Views expressed are my own and not those of Harvard University or Harvard Medical School.

[Dr. David Sinclair]

Full disclaimer is in the show. Notes.