← The Human Upgrade: Biohacking for Longevity & Performance
The Human Upgrade: Biohacking for Longevity & Performance
The Biblical Anti-Aging Fruit That Scientists Are Obsessed With : 1470
00:53:06
Loading summary
Transcript133 lines
- [00:00]
A
This is one of the problems with aging that you have a decrease in the number of lymphocytes. The other thing that we saw was a decrease in inflammation.
- [00:07]
B
People 50 to 70, they took timeline for a month and they saw improvements in their immune system.
- [00:14]
A
After eight weeks, we see a statistically significant improvement in reduction in fine lines and wrinkles.
- [00:20]
B
You could contrast that with one of the things that I've done in my $2.5 million of longevity stuff over the last 20 years.
- [00:26]
A
We see an improvement in mitochondrial function by looking at the increase in gene expression of mitochondrial genes. And this is after a month of taking.
- [00:38]
B
You're listening to the human upgrade with Dave Asprey.
- [00:46]
C
If your light environment isn't dialed in, your biology isn't either. And if you're not using light as a performance tool, you're leaving results on the table every single day. The right light wavelengths unlock recovery energy and clarity in ways most people never tap into. EMR tech's Krypton UV line puts that power in your hands. With red near infrared, UVA and UVB all in one system, they have something for everyone from the compact Krypton Micro and mini to the modular 606 watt and 1612 watt. Each device lets you choose your wavelengths, your timers, and how deep you want to go with your setup. I personally use the Ultron. It's a beast. Full body coverage, built in timers, and high output light from premium components. Whether you're syncing your circadian rhythm or designing a pro level light environment, EMR tech lets you scale it your way with precise control. Go to emr-tek.com Dave and use code Dave for 40% off.
- [01:51]
B
Have you ever finished some kind of weird juice detox and ask yourself, why did I just do that to myself? Well, it's a good question because a lot of those things just don't work and some of them are just not even good for you.
- [02:01]
A
It's.
- [02:02]
B
It turns out your body has detox systems and sometimes you just need to turn them on and give your body
- [02:07]
C
a little boost with binding.
- [02:09]
B
Toxins and the right nutrients can do that. That's why I've been using recovery bits from energy bits. It is an actual food, not a supplement. And it's got just a single ingredient
- [02:19]
C
that I've written about for 20 years.
- [02:21]
B
It's called chlorella, which is a unique form of algae. And when you process it properly, just
- [02:27]
C
like energy bits does, it binds and
- [02:29]
B
removes toxins like heavy metals. So you don't need juices that don't work anyway. And you don't need weird synthetic powders. You can just go for concentrated real food. So if you want a smarter way to hack the heavy metals that are present in all of us because of our environment, this is an easy way to do it. You will not find me eating sushi without my energy bits. So head over to energybits.com, use code ASPREY for 20% off your order. If you've been listening for a while, you know that biohacking, it's about how you control your state. And you can say, I want to be, you know, a balloon animal or you can say, I want to live a very long time. So longevity is central to this. And if you're going to live a long time, you might want to have a working brain and learn how to be happy. So that's why biohacking is so important. And breakthroughs in longevity are something that has fascinated me for 25 years because I used to weigh 300 pounds and had all of the old people diseases when I wasn't even 30 yet. Things like arthritis and prediabetes and the brain fog and just list goes on. I wanted to bring someone who's spent decades working on this problem and actually making it happen. A PhD cell biologist who happens to have been behind some of the biggest research, something that beats NAD and rapamycin and some of the other longevity molecules and something I've used every single day since I first heard about it years ago. And you've heard from others from the company, but never from a co founder of the company. And I'm talking about none other than Timeline. His name is Chris Wrench and he spent decades working on this and done a lot of other work in the life sciences field. So we're going to learn about how you discover something that no one else knows about and what it takes and how long it takes to do that. So Chris, thanks for coming out to Austin.
- [04:26]
A
Thanks for having me here, Dave.
- [04:27]
B
So who are you? How did you get here?
- [04:29]
A
Well, Dave, we started timeline 18 years ago and yeah, a long time. And the goal from the very beginning was to focus and bring the best in class science to nutrition and really focus on the problem of aging and hit it right where it starts. And that's with the mitochondria function.
- [04:52]
B
Eighteen years ago, it wasn't cool to talk about longevity. You could say I want to have new wrinkles on my skin, but you couldn't say I'm working on the core problems of aging. In fact, it Was relatively risky academically to do that, because aging is not a disease. It's inevitable. It all happens. So you are very, very early in the field to do this with academic rigor. What made you care about it so much?
- [05:18]
A
When we started timeline, before I was investing in venture capital in a number of nutrition products, number of nutrition companies, and what we tended to see as investors Were a lot of marketing stories without the deep science behind it. And I thought, there has to be a better way for us to develop products that are clinically validated to actually improve people's health and prevent some of the root causes of aging.
- [05:49]
B
Okay, so you just had this intuition, then. There had to be a better way to do this, and you wanted real evidence. We didn't have aging clocks. We didn't even know how to measure whether things were really working for longevity and for aging. So how did you pick a target?
- [06:05]
A
In the very beginning, we were thinking about what are the cellular mechanisms and processes behind aging. And one of the key ones, and one could argue it's the most important one, Is the decline in mitochondrial function.
- [06:20]
B
So you were very early on that. That was my hypothesis, Given that I had chronic fatigue syndrome at the time, which is I don't have enough energy. So I thought, let's go to the power plants and ramp those up. But the link between mitochondria and aging Wasn't well described back then. So you just had a thought, okay, let's go to mitochondria. And this is because you studied cell biology. Maybe it was obvious for you then.
- [06:44]
A
So 18 years ago, people did appreciate that the mitochondria was very important in the aging process, and it had been seen as one of the key factors and decline of brain aging, also in muscle aging. But over those years, more and more understanding of the mitochondria and the aging process kind of came to light.
- [07:07]
B
We call them stovepipes in the business world. But basically, these separate domains where people are looking at, oh, well, it's really about the liver, or we're looking at a cosmetic thing, or it's something in the blood or it's toxins. And kind of all these different theories in terms of all of them are true to some degree or another. And maybe there's some BS in there, but, you know, is it nutrient insufficiency? And so it's almost like an impossible to solve puzzle, because there could be a thousand ingredients in. Involved in aging. In fact, I In my longevity book, I'm like, look, aging is death from a thousand cuts. I just Take fewer cuts and make them less deep and you'll probably age a lot better. But you ended up just zooming in on something that was pretty shockingly effective. So how do you go from a PhD to pomegranates?
- [07:54]
A
If we go back to the early days when we started the company, the vision was to take this pharmaceutical quality of science and apply it towards natural products to identify specific molecules that are acting on specific pathways. And particular the pathway of aging and the mitochondria was that key target that we were interested in. And so we kept this in mind and we were looking at a number of natural products and one of those was the pomegranate. If you think about the pomegranate, this is. This has been known for thousands of years to be a fruit linked to longevity and healthy life, even fertility. Yeah, yes. And so we thought, well, is there something really to it? There had been a couple of publications talking about giving pomegranate juice to animals and seeing something. And we said, well, let's take a deeper look to see if there's really anything behind it. This led me on a journey and the company on a journey where we went down and I went down, for example, to the south of Spain around the Alicante area, where they actually have a lot of pomegranate orchards over there. And we started looking at pomegranates, we started bringing them up to Switzerland and we started studying them and doing a deep dive into the science of the pomegranate, trying to find exactly which compounds are there and what they're doing. And so we did this whole bioguided fractionation and this led us to the discovery of some really interesting biological effects of the ellagitannins, which is one of the class, the dominant classes of compounds in the pomegranate, the biggest one being a molecule called punicalagen. And we started asking ourselves, well, can these actually work on specific pathways? We looked at punicalagen and we started asking ourselves about its metabolism, even. And. And there had been some studies at the time where they had fed animals and also even humans with pomegranate juice and looked at the various metabolites, the various things are. That are excreted from the body in the urine. And they found a molecule called urolithins or urolithin A in particular as the dominant one. So this is sort of perceived as a molecule that is body's way of cleansing it from the ellagitannins and punicalagen
- [10:28]
B
that it was taking for listeners. If you've read any of the books. These polyphenols, these colored compounds that are in a lot of fruits and vegetables and herbs and spices and other related compounds to polyphenols, they get metabolized in the gut and they turn into things. And that's one of the reasons that coffee is good for you, is the polyphenols in the coffee get used as fuel to transform what's happening in the gut and things like turmeric and blueberries and all these things. It isn't the compound, it's the compound after it gets metabolized, including the microbes in the gut. But it feels like we didn't know nearly as much about those processes 18 years ago because I was interviewing people in the longevity field and we would meet every month in Palo Alto at a non profit that I ended up running and we had a guy come in and talk about the benefits of pomegranates. And I happen to have a tree in my backyard. So I would eat all the pomegranates and then get sore joints because it turns out pomegranate seeds have a lot of oxalates in them, but. And also there's a lot of sugar in them.
- [11:34]
A
A lot of sugar, but it tasted good.
- [11:37]
B
And he was talking about something called palm one, which is a detoxing enzyme that's apparently in pomegranates. Are you familiar with that on pon or palm one way back in the day?
- [11:45]
A
No, I'm not familiar with that.
- [11:46]
B
It's. Who knows, maybe, maybe it wasn't real. I mean, this is a long time ago. So it was a theory and I didn't get great results from it, probably because now, based on the research you've done over the last 18 years, I'm like, oh, I probably didn't have the right bacteria in my gut. So somehow you went through all the possible things that could be in it and you came up with these compounds and you found urolithin A in urine. And how did that lead to timeline?
- [12:13]
A
So we arrived at urolithin A, Dave, because as we were studying the ellagitannins, we asked ourselves, you know, is there something more than the ellagitannins? Is, could that be. Is, is that what's having the deep effect? Or could there be something even more? And so what we did is we took a closer look at the whole metabolic pathway. And as you were mentioning earlier, there's bacteria in our gut that transforms these ellagitannins into urolithin A. And so that makes urolithin A postbiotic. And we said, well, maybe urolithin A isn't just the body's way of eliminating ellagitannin, but maybe urolithin A is something that's very important. It's a molecule that's going to be biologically active in the body. And in fact, it's the bacteria in our gut that's unlocking the biological effects of the pomegranate. And so we took that leap of faith to start exploring urolithin A. And at that time, what we did is we've been working with one of the professors over at the epfl, which is like the MIT of Switzerland. This professor is Professor Johan Oerks, and he happens to be one of the world's leading researchers in mitochondrial biology. And we provided him urolithin A at the time. And we said, well, we think that there's something to this. Let's try it. And he tested it in these worm models that he has. And you may be familiar with these worm models. It's a way of studying aging biology. And basically, worms live to be one or two weeks long. And so they're very sensitive. If you have an impact on key aging pathways, you'll see an extension of their life. And so we provided to them. He said, well, let me try it on our worm models. And so we went away and we were working on other things. And then he called me up one day and said, chris, there's something really interesting here. And basically what they showed was that they were able to improve the lifespan of worms by 45%.
- [14:27]
B
That's a big deal.
- [14:28]
A
It's a huge deal because when you think of it, sort of the gold standard is caloric restriction. And caloric restriction extends the life of worms about 47%. So it's about on the same magnitude.
- [14:40]
B
But the worms are a lot less happy when they have no food, and so are people. So there's that. And how does that compare to things like NAD or rapamycin with worms?
- [14:51]
A
Well, rapamycin is. Is just a little bit less. It's around 40, but it's in the same. It's in the same ballpark. But then that's a. A pharmaceutical.
- [14:59]
B
Yeah, it's a pharmaceutical that in the world of longevity, ten years ago, a lot of people were taking it. And then over time, I tried it for a year or something, but it. It's immunosuppressive and it has side effects, and I don't think it's worth it. And now the science shows it probably doesn't work.
- [15:14]
A
Yeah.
- [15:15]
B
And it and for listeners are like worms. Well, we start with worms because they're easy. And then we move into fruit flies, and then we move into mice, and then we move into humans. And use aging clocks is kind of how we test these things. This is like an early signal that you had something that was really big. In fact, bigger than some of the rock stars in the longevity movement right now.
- [15:35]
C
What if you could make your brain Sharper in just 10 to 15 minutes a day? Focus comes down to how well your mitochondria are working, because that's how your brain makes energy. When your mitochondria slow down, you get brain fog, fatigue, and low motivation. Light changes how that system behaves. Scientists have been studying near infrared light for years because of how it interacts with mitochondria and supports energy production in your brain. And that's why I've been using neuronic. It's a wearable light therapy device for your head that uses near infrared light to support clarity, focus, and overall brain performance. Performance at home. Without adding another complicated routine, it is simple to use, easy to stick with, and fits into your day in just a few minutes. If you're ready to ditch brain fog or you just want better mental performance, this is a straightforward tool to add. Go to neuronic online and use code Dave for $100 off.
- [16:31]
D
So you're running out of closet space. The good news? You don't need to stop shopping. You just need to start selling with The RealReal. The RealReal is the world's largest and most trusted resource for authenticated luxury resale. Whether it's that mini bag that can't even fit your phone or those boots you never fully broke in, the RealReal handles everything from photography and copywriting to shipping and pricing. So you can just sit back, get paid, and make room for things that actually feel like you. And with 10,000 plus new arrivals every single day from top designers like Prada, Celine, Louis Vuitton, and Louisville offer up to 90% off retail, you're bound to find something perfectly on brand to fill that extra closet space with. Plus, this may only you can get an extra $200 to shop when you sell for the first time. Make room for what feels like you. Go to therealrail.com to start selling and get your extra $200 to keep shopping@therealrail.com that's therealrail.com terms apply.
- [17:31]
A
Yeah, for sure. I mean, this is something that really causes us to all of a sudden pause and say this is something really important. We have to take a deeper look at it. And it caused us to then shift and then look in mice to see what the impact was in mice. And looking at a number of mouse models at the time, and what was just really fascinating is when we gave it to mice that were older mice that essentially those mice consuming urolithin A had 40% more running endurance by just, by taking it. And so. Wow. And at the same time we were, you know, we were trying to understand the mechanism of it. So we understood at the same, around the same time of, of doing the worm studies, we, we saw that there was an effect on mitochondria, but we really didn't understand what that effect was.
- [18:24]
B
How did you figure out what urolithin A did to mitochondria directly?
- [18:27]
A
When we were looking at urolithin A and the biology on mitochondria function, the next question was to try and understand what it does. This is a much bigger question because it involves lots of potential different pathways. And it was by going through a number of tests, probably over a year's period of time, that we were able to discover, and this was in the lab of Professor Oerx, that it was acting on a really important longevity pathway linked to mitochondria. And that's called mitophagy.
- [19:04]
B
All right, guys, if you read Superhuman or you've been listening for over the last 12 years of the show, mitophagy is actually one of my fetishes. It's incredibly important because we have autophagy, which is clearing out the cells in your body as they get old and need replacing. But mitophagy is replacing mitochondria that are not pulling their weight. Basically, you figured out that this triggers mitophagy, so that we're getting rid of the dim bulbs, right? And then you tested this on longevity and, and we mentioned the worms. Are there studies on mice, on humans? Like, what's the latest data on what urolithin A can do?
- [19:41]
A
I think it's interesting just to talk about also mitochondria in itself. I mean, I don't know how, how much of your listeners may appreciate the background of mitochondria. We think of mitochondria as a, as just this sort of abstract word, and we don't know how to sort of put it into context if you're, if you're not a biologist. But it's actually, if you think of it, 2 billion years ago, a cell swallowed a bacteria, and that bacteria then became mitochondria and that's really what keeps ourselves alive by producing energy. And it's fascinating. In our bodies, we have about 37 trillion cells. And about 7 of those 7 trillion cells actually contain mitochondria. And the rest are red blood cells. It's really quite amazing when you think about that, because you have these 7 trillion cells and they contain different quantities of mitochondria. So the ones, for example, the heart, your cardiac cells, they need about 5,000 mitochondria, in that order. And then your brain cells somewhere in the 1000-2000, your liver cells as well, and then your muscle is about 1,000. And so if you look at the average, you have somewhere between 1,000 to 2,000 mitochondria per cell. It's a huge number of cells here. You're talking about 7 to 14 quadrillion mitochondria in the body.
- [21:14]
B
So way more of those than cells in your body. Way more mitochondria than even bacteria in the gut. My very latest book, I. I truly believe that mitochondria are the seat of consciousness, where they are making decisions and filtering reality long before our brains do it, because they are the things that sense the environment way before your brain can, just by definition. So there's a lot of interesting implications for the way the ego works, for instance, that come down to bacterial imperatives for survival. And Martin Paul has written some beautiful papers about how mitochondria are a community and how they vote and how they move around and how they have transport things and they're inside our bodies and we can't see them unless you have microscopes. But they are kind of where it's at. If you want to have more energy, well, maybe you should have better power plants. It kind of seems obvious, but it's only really recently in medical history that we even knew what these things were. Right?
- [22:15]
A
Yeah.
- [22:17]
B
So you figured out that you could make them better with your lithium. A. You've mentioned that you have mice. You can run 40% longer. Have you measured ATP production?
- [22:27]
A
We haven't directly measured ATP production in animals or in humans. This is a little bit more complex because there's the fluctuations that happen. It's not just an on and off switch, if you will, but if we think about improvement of mitochondrial function. One of our first clinical studies that we looked at muscle biopsies and what we see when we take these muscle biopsies as we see an improvement in mitochondrial function by looking at the increase in the gene expression of mitochondrial genes. And this is after a month of Taking mitopure at either 500 milligrams in a gram. And that was our first study. And that's where we set up to and identified the right dose to take further into study and additional clinical studies.
- [23:22]
B
So I've. I've tried 500. I certainly prefer a gram a day, which I. That's four pills or two pills?
- [23:28]
A
Four pills.
- [23:29]
B
Four pills, right. And sometimes I take more. But when I was testing out the new Timeline gummies.
- [23:36]
A
Yeah.
- [23:36]
B
I did this on a show and I ate 25 of them or something. I could feel the difference in my mitochondrial function and. And you guys, do you feel your mitochondria? You actually do. There's like a sparkly, vibrant energy when your mitochondria really running. And it's like someone turned up the resolution on reality. You feel more, you think more, and there's just a flow. And I was like, wow, this is kind of cool. It feels almost like a nootropic. Right? And again, this is way more than you guys recommend. I'm not recommending anyone do that, but, hey, I'm the guinea pig. So I feel like there might be some mitochondrial enhancement that's also in there with the mitophagy effects. But whatever it is, I look at all the papers you guys have published, which is way in excess of what most supplement companies would ever do, and I compared that to nad, by the way, I also take NAD precursors and all that. Huge fan of that stuff. Different pathway. But if I could only pick, say, timeline versus an NAD stack based on the numbers, I would pick timeline. But I'm not dumb, so I'm going to do both. Right. You've got this kind of magic compound, but a listener could easily go out there and search for pomegranate extract, and you'll spend 9 to $14 for a bottle of cheap pomegranate extract. Does that do the same thing?
- [24:59]
A
That's a great question, Dave, because it really doesn't. We spent all this time doing all these clinical studies, one, to identify the molecule that is actually giving you the benefits, and that's urolithin A, we call mitopure. And we also found the right dose, and we ran a number of clinical studies, and we don't stop running these clinical studies. And when you take just a pomegranate, a glass of pomegranate juice, for example, you have to recognize that only about 30 to 40% of the people out there have the right gut microbiota to actually transform these ellagitannins in the juice or in the extract into urolithin A. It really wouldn't make sense to take that because you don't know what you would be exposing yourself to, and it would be probably a waste of your money and time.
- [25:55]
B
It's also funny if you can't break down Elijah tannins or other tannins, they're actually plant toxins. And you might find you have to pee a lot if you take one of those because the tannins irritate the lining of your urethra. I have seen some studies saying that pomegranate extract independent of urolithin A could have some benefits from polyphenols in it. I'm not opposed to taking that. I only do 150 pills a day. But urolithin A guarantees that you're getting the result. And we don't have evidence that if you take a pomegranate extract, most of the ones I've seen don't have a specified amount of ellagitannins in them, and they have some other stuff in them. So you could take it, but you have a 40% chance that you can convert it at best, but you're not going to convert it into enough urolithinate to get the results that you've. You've come from because you're talking about a gram of urolithin A. And to make that, you'd have to have an awful lot of ellagitannin. Right, Right.
- [26:54]
A
I mean, I think it all comes down to, you know, what I said in the very beginning, you know, being all about science and taking the scientific perspective in identifying the right compounds and consuming them at the right quantities to trigger these activities at the cellular level at the. With regards to mitochondria and triggering the mitophagy know, you really want something that, you know, works as opposed to, you know, not.
- [27:24]
B
About four years ago, Timeline reached out, and I'm a supporter of this because it. It's fundamental to longevity. And you said, hey, Dave, we've got some skincare stuff now. I'm planning to live to 180 or maybe even longer, and I'd like to have my face that's generally not falling off by that time. So I care about skincare, but I also get sent a lot of stuff that doesn't have a lot of evidence behind it. And I did find myself saying, well, maybe timeline is just trying to extend their product line and, you know, putting urolithin A in skincare stuff and, you know, who knows? But as always, well, here's Our evidence, because you run clinical trials as if you were a pharmaceutical company, which is something I really appreciate. And so you sent it to me and I looked at the research and said, all right, I'm going to try this stuff. And I actually put it on this morning. And, and I, you know, full disclosure, it's not the only thing I put on my face this morning because I have 18 products. And I put. I'm kidding, I don't. But you know, I, I also added some Clotho to it.
- [28:26]
A
Yeah, right.
- [28:26]
B
Which is, is totally fine. And if you're a guy, you're probably going to put one thing on your face if you're lucky, and if you're a woman, you're probably going to put those 18 things on your face. And there's like an upper eyelash serum. I don't even know. It's too complex. But I did put a timeline pretty much all over my face. And I've been doing it for a while and I think it works. But what does your research say about that?
- [28:52]
A
Yeah, well, as you're saying, about four years ago, four plus years ago, we started asking ourselves, and I was asking myself, well, maybe we should be taking a look beyond just oral nutrition and thinking about topical. You know, the skin is our, is basically the largest organ of our body. We have that ability to apply creams directly and act as directly to the skin. So we know we can control the actual dose that is delivered. And so we started exploring that and looking at the effects on skin cells. And then we created a formulation that allowed us to do some clinical studies. And so we started looking at, at the impact on the skin. And we did this by doing all sort of the traditional studies where we did, you know, it's a randomized placebo controlled study where we looked at the effects on wrinkles and. But beyond that, because it's not, I don't find it as a wrinkle cream. You're really sort of trying to go to the, you know, to the origins of skin health, which is your mitochondria. We, we did biopsies in the arm where we applied the skin cream and what we saw was a really interesting effect actually on the gene expression around collagen. And this was very interesting to see that we were able to improve collagen gene expression. We also ran other studies where we looked at inflammation post exposure to uv and we did this on the backs of people. After exposing participants to, to UV light, we applied urolithin A. And what we saw was a control and A reduction in the inflammation by a little bit over 10%. And so very, very interesting to have that type of a benefit, applying it to UV protection after UV exposure. But I think, you know, what's important is the, is the science, the quality of the science. You know, we were doing all the science and we created and we launched this line of topical skin creams. And as they got out there, we started, they started, you know, being noticed by, by other companies and in particular it was noticed by l'. Oreal. And, and so they looked at the science and we were speaking to them and, and, and we were looking at it and they said, well, this is pretty amazing science because we, we don't have ingredients today that you apply to the skin that are acting at the level of the mitochondria and improving their effects. And they got so excited that they became an investor in our company and. Yeah, and that was a couple of years ago. And not only did they become an investor, they decided they wanted to do some joint research together. And so we've been doing joint research together now for over two years. And that's given them that possibility to really take the deep dive among their team. So they have thousands of scientists, but they have a core group there in Paris that we've been working on it and we do sort of hand in hand research together and just some really top quality science coming out of there. We do in vitro work on cells. We do basically a reconstructed skin that we do in vitro. And we look at the effect of mitopure when we put it on these different models. We see improvement in mitochondrial function, we see upregulation of various collagen. And this has got them so excited that they've decided that they want to put it into their products. And I announced that a couple of weeks ago. And there's more on that at the end of this week at the American Academy of Dermatology in Denver, Colorado.
- [32:46]
B
That's incredible. So it's taken about 18 years to come up with a new compound that works better than things we have today. And then to get it from a petri dish essentially, or whatever you were looking at it, and all the way into one of the largest skincare companies on earth, which is remarkable. So congratulations on making a foundational discovery like that. And you mentioned something about UVB or ultraviolet B light. And the sunscreen industry has kind of convinced us that it's bad for you. Except exposure to normal amounts of UVB reduces nearsightedness and it reduces wrinkles. So burning yourself is not Good. But having it as a mild stimulant of your skin is important, which is why I recommend 20 minutes in the sun without sunscreen, without sunglasses. But if you're doing this along with mito pure. Right. Then your mitochondria are getting the stress signal from UVB that causes thicker collagen to form. And they're having the energy because they work better. So from the way I see all this, light's a nutrient. And if you're making the body better able to respond to that form of stimulation, you're going to get better results. So you could put mitopuron and stay in the dark, or you could put it on and get a healthy, normal amount of sunlight and get even better results without needing sunscreen. And if you're going to get more than that, then you can put on a mineral sunscreen, which is what you want to do instead of poisoning your mitochondria with some of the ingredients that are in sunscreen. Does that line up with your PhD level understanding?
- [34:25]
A
There's a lot there to unpack. I think what's, what's really exciting when we think about topical and the use of topical is you were mentioning it earlier. When you consume mitopure, it's improving the mitochondria inside of our body. We can't see that. We can't see that we're improving your heart muscle. Maybe, as you mentioned, you can feel it. You were taking larger doses than you were able to feel it. And depending upon what you do, you can feel it. But what's so exciting about the skin? It's almost a readout for your mitochondria function because you look at your skin and the quality of your skin is really a direct reflection of the mitochondria and their functioning.
- [35:06]
B
It definitely is. And it also, for people, especially if you're 25, gravity affects your skin. And you grow a little bit more skin every year, even if you have very young skin. So you can measure the suppleness, you can measure very fine wrinkles and things like that. But the better your mitochondria, the less of those you get. And at least as far as I've seen, I don't know anyone who's been able to stop gravity over, say, 60. Right. You're going to get some of it. But you can see the difference between someone whose hormones are well regulated.
- [35:40]
A
Yes.
- [35:41]
B
Whose mitochondria, at full power, they look 10 or 20 years younger. Right. And until now, there weren't a lot of ways to get stuff in that were going to affect the mitochondria directly. And so when people use. I guess you had four years of. Of research. Now, do you have quantifiable reductions in fine lines or wrinkles or age spots or anything like that?
- [36:02]
A
Yeah, I think. You know what, we started with just looking at mitopure to understand that. And then we started making formulations and proprietary formulations of mito pure with other. With other compounds. And we've been able to see some very interesting effects on. On the fine lines and wrinkles. After we start to see it as early, just with mitopure alone, we start to see it as early as two weeks.
- [36:27]
B
Is oral or topical?
- [36:28]
A
Topical. Okay, topical. And. And after eight weeks, we see a statistically significant improvement in reduction in fine lines and wrinkles.
- [36:37]
B
Wow.
- [36:39]
D
So here's how you can save up to 70% on your favorite brands from rebel.com has everything for your home, family, and life, from strollers to skincare at unbeatable prices. Every day, Rebel drops thousands of new products for up to 70% off. It's a constant stream of endless deals from brands like Uppababy, Nuna, Baby Bjorn, Nespresso, Breville, Wilson, Dyson, Caraway, and more. Every listing is one of a kind, and the best things go first. So you have to move fast. Save big on your favorite brands. Shop now for up to 70% at from rebel.com.
- [37:10]
B
does it work better if I'm taking it from the inside and the outside at the same time?
- [37:14]
A
It's an interesting question that we've been asking ourselves and the whole concept of a holistic approach to longevity where you take an oral mitophagy activator and you also apply it topically. I think that's the ultimate approach to go.
- [37:34]
B
I want to ask some interesting questions. So we all look at our skin because we can sense our collagen, but your vascular system, your veins, your arteries, they're made out of collagen, too. And we really want a healthy vascular system. So is there an effect on blood flow or healthy cardiovascular because you're taking menopur?
- [37:57]
A
We haven't run clinical studies yet on any type of cardiovascular effects, but there have been preclinical studies that. That show an improvement in cardiovascular function. So. But this comes back to what we spoke about earlier. You know, we didn't stop at one clinical study, and in fact, we've continued to run multiple clinical studies, and we have more than now 15 randomized clinical studies, and some of them with other partners. For example, the one that we did in. That was published in Nature Aging this last year, looking at immune health. And it's this sort of trying to push that boundaries. And I think that's one of the things that's exciting to me is what is that next clinical study that we're going to run that pushes those boundaries? And for me, that one is probably going to be a study linked to the contest called the XPRIZE X Prize healthspan.
- [38:58]
B
I'd have to start one of the X prizes. Okay, you're on the Healthspan 1. Okay.
- [39:01]
A
Yeah, we're in the health Span. And so we were last year, we were among the 40 finalists. And so we are going to apply again to continue. And the goal here is, in the context of the XPRIZE Health Span, is to come up with an intervention for a period of a year that slows down your aging from your muscle, immune or brain by at least 10 years and perhaps even 20 years, which is a very ambitious goal, I have to say. But it's. It's exciting to be in, you know, participating in that. And I think that's, you know, when you think about the future is, you know, what we're trying to do is establish urolithin A as the most clinically investigated longevity nutrient that exists. And that's the pathway that we're on today.
- [39:56]
B
I think you've done a remarkable job on that. And it's funny because I learned in Silicon Valley during my career there that the best technology almost never wins. And it's. As a technologist, this actually causes me pain. I'm like, but this one is smart and this one is stupid, and everyone's buying the stupid one. And I realized it's because of the power of marketing. So if you're an inventor and you make the best thing and no one ever uses it, you're a failed inventor. And a lot of inventors, like, this is my precious. And then they never let it go, right? They never bring it to the world. And in this case, there's a lot of compounds like resveratrol. We've been using that stuff for 40 years, right. And it's kind of well known in longevity circles. And it probably has an effect, Right. And maybe stacked with other things. It does. I've been taking it for a long time or some of its cousins, but the evidence is far thinner, yet it's way more famous. And what I like with what you're doing is you have a very clinically valid methodology or just, like, measured approach in how you're bringing it out there, and you're not doing the aggressive marketing thing that happens where people create kind of a flash in a pan where you're saying, like, this is real, it has mass behind it, and so you're bringing it out into the world. It takes more time that way. But if I put on my futurist hat, you look out three years from now and you're going to see more and more people talking about timeline and mitopure as being one of the most important things you can do that's affordable. And that has really good results. And in my stack, it's right up there with NAD as having pretty good evidence behind it and maybe less complexity than nad, because there's a lot of stuff we don't have to get into on this episode. There's plenty of others about that. And David Sinclair has been on the show multiple times talking about nad. So I just feel like you're not doing the flashy marketing thing, but you're just educating. And I appreciate that because like I said, I've been using this stuff since you guys first launched it because I looked at the evidence, said that's going in my stack. And, you know, there was two of the big red pills in it this morning and there'll be two this evening. And I just do that every day.
- [42:14]
A
You really need to have great science and you need to publish it. So it needs to be peer reviewed. And, and that's the key. You need to have a certain level of transparency on the technology, especially when it comes to, you know, nutrition and health and, and even topical products. I mentioned some of the research we've been doing with l'. Oreal. In fact, right now we're in the process of taking that and submitting that for publication. So this is an important step for every scientifically based technology.
- [42:52]
B
With mitochondria, we can say, well, let's look at brain function, let's look at runtime in mice, which is a marker for cardiovascular function. Let's look at wrinkles, and let's look at aging clocks and cells and things like that. What I've learned over the years is if you want to fix anything in the body, make mitochondria work better, and you'll see a result because they power everything.
- [43:14]
A
Right?
- [43:15]
B
Right. And so I've put all of my. All of my bet is starting in the late 90s behind mitochondria. And it turns out most of the other things, even things like thyroid hormone or testosterone, estrogen, direct effects on mitochondria. So when you have a mitochondrial centric view on aging, not the only thing that ages you. It's just all the other things that age you are powered by them. So you should get those working. And that usually fixes downstream. So I would bet that the results of your study on cardiovascular stuff is going to be positive because, wait, there's more mitochondrial density in the heart. And if you look at brain aging. Oh, there's a lot of mitochondrial density in the brain. And you look at immune aging. Well, we know very well that mitochondrial function drives immune function. Right. So I'm pretty sure that timeline is going to have good effects across all sorts of systems that you may never study, including like eyelash muscles or something, I don't know. But like things that no one's going to ever study.
- [44:13]
A
But what's exciting is that the scientific and medical community are starting, and not only starting, they're getting more and more excited about urolithin A and mitopure. And what we see is a lot of principal investigators approaching us with different clinical studies that they'd like to run on mitopure. So we have a number of those that are sort of, that we're discussing with right now either in the CNS area as one example. And so we receive a lot of these requests. And in fact, we have a couple studies right now when one with the National Institute of Aging and another one with the over in Germany where we're, where we ran the previous study on immune health. You're looking at people who are post cancer and looking to see how that impacts their immune system. Yeah. And so I think this is the importance to really get people interested, get scientists interested, get clinicians interested in, to run all those studies because as a small company, we can't do everything. Of course, we continue to innovate and to conduct more studies to explore how it can benefit us. But it's having this global network effect. That's what's the most important.
- [45:33]
B
Did you ever, one night when no one was looking, purify some mitopure and maybe drip it into an IV bag in your arm?
- [45:42]
A
Interesting question. You know, there is a lot going on with IVs these days. We're not taking that route of doing the iv.
- [45:51]
B
I think that was a yes.
- [45:53]
A
No, we've not explored that. Because you haven't studied it at all. No, we haven't.
- [46:00]
B
Can I be your guinea pig? Unless it clumps up and causes blood clotting, it would probably be really potent to get it in.
- [46:07]
A
Well, I think one of the challenges with, with any of these actors are our solubility at the right doses. And I think also that once you start going iv, you start to go into the direction of more of a pharmaceutical product. And I feel like you really want to be under the care of a physician when you do the pharma.
- [46:31]
B
Yeah, of course.
- [46:33]
A
And here, the whole point of what we're trying to do is democratize this science for a wider public. And I mean, that's what's so exciting when we, you know, when we're able to get it out there by, you know, through coming on, you know, your podcast and actually working with companies like l', Oreal, who tens, maybe even hundreds of millions of customers around the world and just to help educate people more about the benefits of urolith and a. Because in the future, if we're, if we're thinking, you know, really in the future, I think everybody should be taking this, you know, as part of their morning routine.
- [47:15]
B
It's funny because, you know, IVs and subcutaneous injection are all the rage because peptides, some of the larger ones, require that. But small molecules and fat based molecules can enter the skin and go systemically. That's why a lot of the chemical sunscreens are not good for you because they're basically giving you a sunscreen iv, which is bad. So using it topically could be equally or even more effective. And there are even a few peptides out there, the very small ones, that actually enter the skin just fine. So I like the idea of put on the timeline on my face and then I take a gram a day and sometimes more if I just feel like it, and I feel like I'm probably getting enough. But if, if there was some company out there who wanted to buy a bunch of your stuff and do all the pharmaceutical side, well, then they should call you because they're. Who knows? Like, I want to see this, I want to see the science. Someone has to do it. And probably mouse IVs are hard to do.
- [48:11]
A
I'm guessing we've really focused on, on more oral interventions.
- [48:15]
B
Oh, totally.
- [48:16]
A
Yeah.
- [48:16]
B
Just looking at the future.
- [48:17]
A
But yeah, no, it's, it's interesting. Yeah, it's. You never know.
- [48:25]
B
You published something recently in Nature Aging about timeline.
- [48:29]
A
Yes.
- [48:29]
B
What did that study show?
- [48:31]
A
This was a study that was conducted over in Germany. And what they looked at was, and it's the first time we've tried this, the group looked at administering 1 gram of Urlithin A for a period of one month in a population that's around 50 to 70 years old. And what they did was they looked at from the baseline to the one month period. After a one month period, they saw an increase in the number of CD8T naive cells and also an increase in the NK cells, which is very important. I mean, when you think about just increasing your lymphocyte populations, this is one of the problems with aging that you have a decrease in the number of lymphocytes. The other thing that we saw was a decrease in inflammation. And we all know that as you get older, there's the whole story of inflammaging. So this was something that was very, very interesting. And we looked and we did a whole screening actually of the mitochondria function and the mitochondria presence inside of these cells through a fax analysis, which is this, this complicated way of looking at in a very detailed manner what's happening in all of your lymphocytes. And what we saw was an increase in the mitochondria, in gene expression related to mitochondria and an increase in the mitochondrial function. So showing that we could actually have an important impact after a one month period.
- [50:05]
B
Okay, that's huge. It's not long, it's not expensive, and you guys just cut the price, which I appreciate. And this is people 50 to 70, they took timeline for a month and they saw improvements in their immune system.
- [50:19]
A
Yes.
- [50:20]
B
That's. Yeah, that's amazing. You could contrast that with one of the things that, that I've done in my 2 1/2 million dollars of longevity stuff over the last 20 years. I did a procedure, cost about a hundred grand where we took 19 vials of blood, pulled out my natural killer cells, cultured them so we could grow a lot more of them, and then injected two point something billion of my own natural killer cells back into my body to make my immune system younger. Right. So that's a lot of bottles that might appear. So sometimes we know NK cells matter. We know these naive CD8 cells. And naive means that they aren't programmed to be inflammatory. They're like, oh, we're not worried, we're just going to chill in case there's a new threat versus threats. But we know that as you age, if you can do these things, it makes a huge difference over time. So I was willing to do odd things that biohackers do to, to show it's possible.
- [51:20]
A
Yeah.
- [51:21]
B
And sort of the, the method for me is I'll go do the things the crazy billionaires are doing. Although I, I'm still aspiring to be a crazy billionaire. I just have the Crazy part. And actually I don't even care about the billionaire, just like to have enough. But the idea is let's do the extreme because that's where we're likely to see a result to go, aha, it does work. And then we back down and say, well, what makes it affordable? So if I was writing a new longevity book, I say, well, here's NK cells, what the crazy billionaires do. Here's the affordable path for NK cells. And if I could find a free thing that increased NK cells, like kind of fasting or something, I'd say, well, here's the free thing. But NK cells matter. So the fact that you just came out with this in a very affordable, in a very short period of time, this is something that in the longevity world we should be shouting this from the rooftops. So congratulations on that research.
- [52:11]
A
Thanks, Dave. Yeah, it's impressive to see the body acting and reacting so quickly and during a one month period. And so this is something. It's the first study that we've done on immune health and as I said, this was run by another group. So we were simply providing the midopur there.
- [52:29]
B
Hold on, I thought you were doing studies like Big Pharma. You're supposed to be providing it and the funding and then making sure they only say what you want. So you don't have any control of this study. I mean, come on.
- [52:40]
A
Well, Dave, we.
- [52:42]
B
So you actually really did the proper research and I do respect that.
- [52:46]
A
Yeah. So I mean, in this particular study with our German colleagues there, but we've been working with them now for a number of years. They had actually started out publishing initial studies and this was published in a journal called Immunity. And based on that science, they wanted to do another study. As I was mentioning earlier, there are a lot of principal investigators that have come to us interested to stimulate mitophagy in different type of clinical areas.
- [53:19]
B
I'm just seeing all the different organ systems benefiting from matterpeer. So this is really cool research. And because I know what it's like to spend more than a decade on an idea and just to keep pushing and pushing and do the research and congratulations. I think you've done something impressive for longevity. And you guys can get 20% off. Go to timeline.com Dave or just use code Dave. And that's something you might want to try. Get a month supply. Because you just saw that one study doesn't mean it's always going to work for every single person. No company can make that claim. But given that better mitochondria are kind of good for all of us. And I think it's something that should be in your longevity stack and now it's more affordable. So what is the ideal daily routine for using timeline?
- [54:04]
A
We've run a lot of studies and we think that that 500 milligrams is really the right dose. That's why it's the dose that we're commercializing today.
- [54:13]
B
And so only 500 or at least 500.
- [54:16]
A
At least 500. And the idea would be to take that consistently so you can take it in the morning. Most people like to take it in the morning. Most of our clinical studies are in the morning. It doesn't matter if you're taking it on fasting or fed, so both will work. My op is that you continue to take it. It's not something that you're going to feel an effect after one day. Even though I mentioned that you can take it for one month and you can and your body will feel the effects. For you to really feel the effect, it's best to take it for about two to four months and take it continually.
- [54:51]
B
I'm happy you said that if someone gains or loses a pound or two in a month, you're not going to see it.
- [54:56]
A
Right.
- [54:56]
B
You might measure on a scale, but you just won't see it because the change is gradual. And some things, like if you're taking a cognitive enhancing nootropic formula, and I've formulated a bunch of those over there, you really should feel that. Right. If it's the right one for your brain. And if you're taking something like a phenylpiracetam, like these kind of aggressive things, or modafinil, like, okay, like. Or coffee, like, if you can't feel it, it was decaf, right. Or maybe it was moldy. This is one of those things. Also like mineral supplements, unless you're really deficient, you're not going to feel them. But you know, over time your bones are going to get denser. So this idea of up to four months and of course you can do. I've been doing it for years. But up to four months, consistent use. If they skip a day every now and then, who cares? But if you just take it, oh, you know, today's a big day. I'm just going to take Mitopur. That's not how this one works.
- [55:44]
A
No, it's not a stimulant. So you really need to have a consistency over a prolonged period of time. And we have now, you know, tens of thousands of people who have been taking mitopure for many, many months. And, you know, and many people like yourself who've been taking it for years, they all love it and they come to us and tell us, you know, the benefits that they're feeling.
- [56:07]
B
So I'm. Yeah, I'm a true believer.
- [56:10]
A
Yeah, no, I think it's. We're in a really exciting time, I think, for mitochondria health. And. And as you were talking about the future, what could be the future? I think one thing that we're missing now for mitochondria health is, is to have that blood test that measures your mitochondria level. Right. You know, wouldn't it be great if we could just do a blood test? See, what if we're at, you know, 50% or 20% and then say, okay, we're just going to dial it in with mitopure, or, you know, oh, my gosh, there.
- [56:43]
B
There might be a test for you. Dr. Emil Patel from UC San Diego has been on the show. Really fascinating guy who just came out with a mitochondrial test that he launched at the biohacking conference, I think, three years ago. Have you connected with him?
- [57:00]
A
I don't think we have connected with him yet.
- [57:02]
B
So he's one of my favorite mitochondrial biologists.
- [57:04]
A
Oh, wonderful.
- [57:05]
B
And would be a good condition. I'll make that connection offline.
- [57:08]
A
Okay, great. Yeah, I mean, this is, you know, in the future, this would be very important for us to have biomarkers to monitor that. And I think it also will help people to appreciate the benefits of. Of all the interventions they do. You, you know, you talk about taking stacks of multiple products that are acting on mitochondria. If we can just follow that with time, that would be great.
- [57:31]
B
So, yeah, much a lot of respect and a lot of appreciation. So thank you.
- [57:34]
A
Thanks, man.
- [57:36]
B
See you next time on the Human Upgrade Podcast.
- [57:44]
E
The Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of. Of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media.