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While none of us can change the number of times we’ve gone around the sun, we can affect the rate of aging in our body. This is what’s known as healthy aging. Thorne HealthTech’s Chief Science Officer Dr. Nathan Price sits down to share the groundbreaking science behind healthy aging, longevity, and extending our health span.
During this episode you’ll learn about:
Resources to topics mentioned in this episode:
During this episode you’ll learn about:
Resources to topics mentioned in this episode:
Dr. Robert Rountree:
This is The Thorne Podcast, the show that navigates the complex world of wellness and explores the latest science behind diet, supplements and lifestyle approaches to good health. I'm Dr. Robert Rountree, Chief Medical Adviser at Thorne and functional medicine doctor. As a reminder, the recommendations made in this podcast are the recommendations of the individuals who express them and not the recommendations of Thorne. Statements in this podcast have not been evaluated by the Food and Drug Administration. Any products mentioned are not intended to diagnose, treat, cure or prevent any disease.
Dr. Robert Rountree:
Hi, everyone, and welcome back to The Thorne Podcast. Joining me this week is Dr. Nathan Price, the Chief Scientific Officer at Thorne HealthTech, the CEO of Onegevity prior to its merger with Thorne, more on that later, and a researcher who is named one of the top 10 emerging leaders in health and medicine by the National Academy of Medicine. How're you doing, Nathan?
Dr. Nathan Price:
I'm doing great. Wonderful to be with you, Bob. I appreciate it.
Dr. Robert Rountree:
Yeah. I'm really looking forward to actually having a little time to chat. I'm wondering if you can tell people who the heck you are. I know we could talk about your resume for a couple of hours. But maybe you could just give people a little bit of an overview and then tell us kind of how you got involved with Thorne.
Dr. Nathan Price:
Yeah, happy to. So I'm a scientist and I try to be an entrepreneurial scientist. I'm very interested at the interface of what can we learn and how do we translate it to society. And that's a long time interest of mine. In fact, the quote of mine in my high school yearbook is, "What I want to do in the future is invent something and start a company." I've always been interested in science and business for a long time. And so it's kind of interesting from that perspective. So in terms of my background, I have a PhD in bioengineering, which I did on building what are called genome-scale metabolic models, big computer models of how do you take nutrients that you take into your body and how to do all those biochemical processes work to create you. So that's been a long term interest of mine.
Dr. Nathan Price:
I was Professor and Associate Director of the Institute for Systems Biology for about a decade. In the last few years, I was there, I had a really interesting opportunity. Lee hood, who had been my mentor as a postdoc, and then I had gone back to ISP after a stint, as an assistant professor at the University of Illinois in Urbana, basically, came to with the proposition of merging our lab groups together. We had become both very interested in this area that we call scientific wellness or you could call it precision health. We'll talk a lot more about that. And so we ran a joint lab, The Hood-Price Lab for Systems Biomedicine there. Started a company at that time. We co-founded a company called Arivale together.
Dr. Nathan Price:
And through those efforts, we analyzed huge datasets on about 5,000 people where we had genomes and microbiomes, and metabolomes, and proteomes, and information about what people were doing in their health, working with health coaches up to on a weekly basis, at least monthly. And so we had this wealth of data, and I got really interested in not just what do you do after disease, we had a whole bunch of papers, 100 papers may be in systems medicine. But got much more interested in how do we stop disease before it starts? And what signals are there in the body that tell us that something is going to happen? How far can we push that? And so I became very interested in that as a topic.
Dr. Nathan Price:
About a year and a half ago, I got a call from Paul Jacobson, who's the CEO of Thorne with an interesting proposition, which was to come on, become ultimately the CEO of Onegevity. But really, to fold all of this together, and I still remember what he said to me. He just said when he reached out ... I'll just share this because I was planning to say no to him. I was very happy. I had this great job. We were doing this. I was very excited about what Thorne was doing. We had done a little bit in terms of a joint venture, but I had a million things to go. I was going about to say we're doing all these studies, we've got in the process of starting three different companies, and we're going to do 12 clinical trials. I just had this whole litany of things that I was going to go through.
Dr. Nathan Price:
Paul kind of short-circuited me right off the bat and said, he said, "You know what the problem with all you academics," says, "you want to have your hands in a million different things and you can't see the one huge opportunity that is staring you in the face." And he said, "If you really want to take all these things you're doing in scientists wellness, all this science that you're doing, and you want to make it really have impact in the world," says, "you've got to tie this all up into one thing." He says, "You come," he says, "I'll run business and you do science, and we'll build the greatest healthy aging company in the history of the world." I walked away from the call and I thought, I should probably listen to this and think about it. So that's how I got involved with Thorne.
Dr. Robert Rountree:
Well, fortunate for us. It seems like the whole team that Paul Jacobson has put together is pretty amazing. I think you'd agree with that.
Dr. Nathan Price:
Absolutely. So many great people that have been engaged. I feel like I'm still meeting amazing people across all the different buckets that go into Thorne HealthTech, which I guess we'll talk about a little bit more.
Dr. Robert Rountree:
Sure.
Dr. Nathan Price:
Yeah. It's an incredible team across many, many different areas, for sure.
Dr. Robert Rountree:
So it seems like this interest in preventive medicine, and really, it's advanced preventive medicine. In the mainstream when they talk about preventive medicine, they're basically talking about mammograms and colonoscopies and things like that, which is not really what you're getting at. You're getting at being able to pick up on early signs that something is wrong.
Dr. Nathan Price:
Right.
Dr. Robert Rountree:
Correct with that?
Dr. Nathan Price:
Yes. Exactly. And it's really about having a different focus. Because if we think about health care in the world ... A lot of people say this, so this has become kind of a common phrase, but it's true, which is that healthcare today is really disease care. Most of medicine today is wait until you have a significant problem, and then diagnose a drug and give it. In fact, I don't need to belabor this point, we all have ourselves or friends or so forth, who have literally gone into the doctor, explain what they're starting to have an issue with, and been told come back when the symptoms are really serious so I can prescribe the drug. So the whole notion of ... Lee Hood and I are actually writing a book on this. It will come out next year. Actually, it's written, it's just in review now.
Dr. Robert Rountree:
Great.
Dr. Nathan Price:
But essentially, is about how do we have a wellness-centric view where our whole mindset is not I'm going to wait till I have some serious problem and where I can justify the side effects of the drug, but rather, how do I improve, enhance, extend health span? How do I stay healthy for longer? Vibrant and energetic and all those kinds of things. And how do we do that in a sense that we have a focus on health that is proactive at looking at initially small deviations that can probably be corrected easily, rather than waiting until we have significant deficiencies that are very hard, if not impossible to put back together.
Dr. Robert Rountree:
You mentioned a word that I want to key in on for our listeners, which was health span. I'm wondering, since we want to focus during this particular segment on healthy aging, maybe you can distinguish health span versus lifespan and why researchers, scientists think that that's an important distinction.
Dr. Nathan Price:
So lifespan is pretty obvious, right? How long do you stay alive? There's a lot of debate in the scientific community about whether or not lifespan can be pushed out a lot?
Dr. Robert Rountree:
Can we be 150, live to be 150?
Dr. Nathan Price:
Can we be 150? Can we be 300? Those kind of things. And we all laugh because no one has made it that far, so far, as far as we know.
Dr. Robert Rountree:
Unless you're a turtle or certain sharks, I guess.
Dr. Nathan Price:
Yeah. But turtle ... And so they're all these tantalizing examples where we can extend lifespan in animal models, and sometimes pretty significantly. So there's all kinds of ... Anyway, without getting all into that there are questions about that. But what's ultimately what you could do in lifespan? Now, the flip side is if you talk to someone about even extending lifespan, a lot of people will say, I don't want that.
Dr. Robert Rountree:
Exactly.
Dr. Nathan Price:
Why? It's because you have this model in your head, I'm going to get old and frail, my mind's going to go. I don't want to drag out for years. And actually, I'm very much in that camp. Who would want? And we could get into all that, right?
Dr. Robert Rountree:
Yeah.
Dr. Nathan Price:
But healthspan is something that is, I think, hard to be controversial. It is what is the length of time that you have a healthy, enjoyable, vibrant life. And we know for a fact that you can extend healthspan significantly, and you can do so through very simple things. Exercise, extend your health span massively, good diet extends it. There are different compounds, which I'm sure we'll talk about, that have been shown to extend healthspan and animal models and so forth. And so it's really about just how do you take that health that is the cornerstone for a good life, and how do you make that last as long as you can?
Dr. Robert Rountree:
So this kind of brings up the million dollar question which is, is healthspan mainly a result of what we do, or is there an underlying program in our cells that affects aging that's more important? Or are we kind of stuck with our genes? Or what about lifestyle? What does nature and nurture have to do with the whole process?
Dr. Nathan Price:
Yeah. It's definitely a combination of both. But healthspan for most people is very modifiable. And so for the majority of us lifestyle is going to be the bigger component. But they do have interesting interplay. For example, a study that we did a few years ago, we published this in Scientific Reports in 2019, showed that we were looking at people who were going through a wellness program, so trying to get better, was the one we used to run. And as they were doing that, we actually looked at genetic signatures, in this case for whether or not a person was likely to have high LDL cholesterol, the so-called bad cholesterol, or HDL cholesterol, so-called good cholesterol.
Dr. Nathan Price:
And it turned out that if we monitored people going through a lifestyle program, and whether or not they were able to lower LDL cholesterol, the genetic signature predicted who would succeed at that and who would not. And the top 40% of people, so a big number, were not able or did not in our studies show a statistically significant ability to lower LDL cholesterol, where the bottom 40% did vary significantly. By top and bottom, what I'm talking about is you can actually build a prediction model off of the genome for the level of a biomarker associated with health. And then you can take the difference or the delta, I'm an engineer, so we call these deltas. But if you take this delta, it turns out that the difference between your actual measure and the genomic predictor is a big sign of whether that biomarker is easily movable or not.
Dr. Nathan Price:
And so what you can do, in fact, is build a plan or a guidepost for people that says, what are all the biomarkers associated with health, where you deviate the most from your genetic prediction. It tells you where you're having a big impact from lifestyle, and these are the things you're most likely to be able to change via lifestyle. And so there is this really interesting interplay. I actually think that the delta between your genomic prediction and your actual value is a whole new category that needs to be implemented across medicine, because right now, we take the measurements of somebody on all these standard clinical labs, in the absence of the genome. So we do not know, today, in 99% of practices, what if that high value is driven by the genome or by lifestyle? And it's hugely important in terms of how modifiable it is. Anyway, there's a lot around that, that's super fascinating.
Dr. Robert Rountree:
What about something like blood sugar? I bring that up, because some people will assert that the genes that are involved in insulin signaling and how your body handles blood sugar are the most important ones to consider when it comes to aging. Alzheimer's is diabetes of the brain, that kind of thing. And animals or even worms that have genes that allow them to handle glucose better, live longer. So would what you saying apply to that?
Dr. Nathan Price:
Yeah. I'll give you two pieces of evidence sort of on each side because, again, it comes down to the kind of the fraction of impact. So your genes definitely do matter and they'll matter a lot, certainly, for certain biomarkers you might find. So if you look at something like hemoglobin A1C, which is a, for our listeners, is a marker that's commonly used for diabetes. It looks at the glycation or the small sugar that get put on the outside of the protein.
Dr. Robert Rountree:
It's your average blood sugar over time.
Dr. Nathan Price:
Your average blood sugar over time, basically. But there are genetics that are associated with residence time of red blood cells. So how long in your body? So some people they're going to last about 120 days, some people that might be longer, 130, 140. And so the longer that they have residence time, the more time they have to accumulate like oscillations. We're actually in a clinical trial on this. So the way you interpret that measure is, again, influenced by something in the genetics, which again, is not done today. So there are all kinds of things that you can look at that way. Now, the counter argument to genetics being the primary driver of sugar issues is that we are experiencing a epidemic of things like diabetes and obesity, and the human populations genome didn't radically change over the [inaudible 00:15:03].
Dr. Robert Rountree:
We don't have new genes.
Dr. Nathan Price:
We don't have new genes. We have new environment and the environment has caused an epidemic. So the argument against genes being the whole story is pretty strong. So it's not the whole story. It plays a role. There's no doubt about that. But it's really the gene by environment interaction that is kind always the answer. It sits somewhere in there. It's just a fraction which one is stronger?
Dr. Robert Rountree:
Well, you and I have already talked about this offline. But there's a lot of excitement these days about these epigenetic clocks that tell you, supposedly, what your real age is, as opposed to the age that you might determine by measuring your blood sugar or your weight or your blood pressure, or things like that. And it seems like the problem that you and I were talking about with these epigenetic clocks is they don't necessarily reflect how you're living. They seem to be a whole independent phenomenon.
Dr. Nathan Price:
Yeah, it's really fascinating. So the epigenetic clocks, a lot of people are interested in them. They were discovered initially and a lot of work has been led by Steve Horvath, a terrific scientist down at UCLA who I've known for a while. So these epigenetic clocks are fascinating. And so I'm a big fan of them from the standpoint of what we might be able to learn as we go down that route. We do have a biological age test at Thorne, as you know, and we don't base it on epigenetics, we base it on a set of clinical markers. The reason we do that, and there's actually papers published, including by Steve Horvath and another just very top aging researcher, Morgan Levine at Yale, know that go into this and do a comparison.
Dr. Nathan Price:
The biological age from clinical labs today is more associated with health outcomes, with incidence of disease, and so forth, then our biological age is based on epigenetics. So we use those because they're more predictive of health outcome today. Because they've been studied for so long, every one of them gives us very specific actionable items of something we can do that we don't yet have around epigenetics. So I love epigenetics from a science point of view. I think it's fascinating. People want to do a test on it, go for it, I think, great. But we like primarily the clinical lab test just because it's more health actionable, more predictive of health today.
Dr. Robert Rountree:
I just want to point something out about the biological age test that Thorne offers, which is the first time I looked at it, I thought, well, this is what I'm already measuring in clinical practice, a chemistry profile, blood sugar, things like that, that seem fairly basic. And then I talked to you about how you arrived at that, and it turns out, you arrived at that from computing huge amounts of data. So it wasn't like you just said, hey, I think a chemistry profile would be a good thing. This was what you came up with after looking at thousands of patients.
Dr. Nathan Price:
Yeah. We initially did this study on about 3,500 individuals, and we measured 1,200 different analytes out of the out of the blood. And you can derive biological age on a wide variety of different sources. And you do get a bit of a different answer, depending on the one that you do. And you're getting different information. So we looked at metabolites, we looked at proteins, we looked at clinical labs, the ones we ended up going with. And so we did go in there and we were able to show that even when we reduced down to this set, I think, ultimately of 36 different markers, that we could keep 90, 95% of the information that we got from the 1,200 in terms of being able to predict health outcomes, which is what we really cared about in terms of its relationship to disease, and also whether or not if you were taking action that would improve your health, you would see it go down.
Dr. Nathan Price:
When we did that initial study, what we saw was that over the course of the years we ran that study, and we ran it ... People came in and out at different times. So it was a total of four years, but each individual length was different into there. But what we saw was that we saw an improvement in biological age of 1.16 years per year in the program. By improvement, I mean, the difference between the biological age and the chronologic age. The way we develop the test, this is also important, it uses something called the Chimera de ball algorithm. And I won't go into the details of that, but it has one important property, which is that it forces the algorithm to learn a biological age such that the expectation is that on average people will go up by one year per year. And so reason that that is really important is that it gives you a measure that you can look at longitudinally. You can monitor year over year.
Dr. Nathan Price:
So when we did that, we saw that women did particularly well. They were getting better at a rate of one and a half years per year during the years on that program. Men were getting better at 0.8 years per year, meaning they were aging 0.2 years per year by the biological age. Women were actually doing better. They were getting a little bit biologically younger, according to the clock. And so when we look at those kind of things, that gave us some confidence in the test, because we saw that positive delta ages, so your biological age being higher than your chronological age was associated with diseases, higher incidence of disease, and people going through trying to improve their health were able to improve this score.
Dr. Nathan Price:
Now, you can't improve it forever, and the lower your biological age is compared to your chronologic age, the harder it is to keep pushing it down. You can't push it down forever. But you can have a positive impact on it and you can watch it. And so even though we now use the pretty standard clinical labs with a couple of extra things in there like DHEA, which gives us a view into hormone health, those are run through a very different kind of algorithm. So it focuses more on where are you were at compared to where you might want to be for your age and your sex and those kind of things.
Dr. Robert Rountree:
I think this is a fabulous information. Just to point the obvious, we know that if you get a roomful of people who are all the exact same chronological age, you see huge differences, right? Some people look like they're 60, some people look like they're 50, some people look like they're 70. So there's clearly huge differences from person to person in terms of what's really going on. And that's what we call biological age, which is What's the age of your body, your organs, your tissues, as opposed to your date of birth?
Dr. Nathan Price:
Exactly.
Dr. Robert Rountree:
And I think what you're saying, from being able to look at the simple markers, instead of 1,200, you used 30 ... Did you say 35, 36 markers? And then you can tell people to do these basic things, to exercise more, lower their blood sugar, take care of their liver, really basic things, and that changes their biological age. So we can't change their chronological age, but we can decrease, at least, the rate at which they're aging biologically. And that's profound.
Dr. Nathan Price:
Absolutely.
Dr. Robert Rountree:
That's profound.
Dr. Nathan Price:
And one of the things I love about biological age is that it is an example of what we call a metric for wellness. So we would like to have tests that aren't just do I have this disease? Do I not have this disease? Want our tests where you can focus on getting a better score, an improvement in health. And so this is a kind of a first version of that. But I love the notion of having a sense in your body, are you clearing senescence cell well? [inaudible 00:23:00] the big hallmarks of aging? Are you dealing well with oxidative stress, which is another big element? Is your immune system on high alert all the time or do you have chronic inflammation? Et cetera, et cetera. And so having just insight on all those different processes and what you can do, either through lifestyle recommendations, or when appropriate, targeted interventions of the kind that we might do from Thorne. And so there's a whole host of steps that you can take to just look at where you're at, what's going right, and where could you use some benefit.
Dr. Robert Rountree:
Wonderful. Well, let's take a short break. When we come back, we'll answer some questions that have come in from the community. So I think we can get a little bit more specific about where we go with all this information. Although getting older is inevitable, you can control how well you age and Thorne offers a variety of solutions to help you do just that. Thorne's biological age test utilizes a blood panel that analyzes the rate of aging for your entire body and its various organs and provides specific recommendations to help you slow or improve the aging process.
Dr. Robert Rountree:
Thorne also offers several science-backed formulas that promote healthy aging from nutrient-rich NAD+ Boosters to collagen powders, so you can age better inside and out. Find the right formula for you by taking Thorne's healthy aging quiz and get real recommendation from Thorne's medical team. Learn more by visiting thorne.com/healthyaging. That's T-H-O-R-N-E.com/healthyaging. And we're back. So now it's time to answer questions that have come in from our community. The first question that has come in is from a listener who asked, Why did Onegevity merge with Thorne? So Nathan, I'll turn that over to you. Why two companies becoming one?
Dr. Nathan Price:
Yeah. So it really came down to what our goals are with Thorne HealthTech. What we're trying to do is to build a integrated deep solution for healthy aging. And so Onegevity as an AI platform, and the knowledge that we were building there just made a lot more sense when you put all the pieces together. So as we're working at Thorne HealthTech, trying to have this big integrated solution, we have 300 different products. But it's not just about what they are, it's about what is the health intelligence that's necessary to deploy them in the right way, the right person at the right time? And that's where Onegevity fits in. We also have another company that we bought into this called Drawbridge, which will deliver at home, blood measurement devices, and so forth. So there's all these pieces that we're putting together to form this cohesive, unified approach to trying to give people the best possible data, information and solutions and healthy aging and those things needed to be rolled together.
Dr. Robert Rountree:
In other words, it's not just about supplements anymore. It's the whole deal.
Dr. Nathan Price:
That's right. And that was really what Thorne HealthTech was about, which is Thorne is, obviously, an amazing brand, probably the highest quality supplement maker in the country. But that's not the ultimate goal of what we're doing. The goal is to extend healthspan and to do that in deep ways, and that's what the mergers are all about.
Dr. Robert Rountree:
So back to the aging topic, who are the oldest people, the centenarians and above? And is there anything that they do that they have in common? I always hear these jokes about the woman who gets up and has a cigar and whiskey for breakfast every day and live to be 115.
Dr. Nathan Price:
Absolutely exist.
Dr. Robert Rountree:
It totally exists. But are there their habits that they found in the research that are going to help you live that long?
Dr. Nathan Price:
There are. And if you're going to be one of those really oldest people, you probably have to both win the genetic lottery and the lifestyle-
Dr. Robert Rountree:
And the lifestyle thing.
Dr. Nathan Price:
But there are commonalities. The biggest factor that influences longevity, and it's quite interesting, but it's been reproduced in a number of different studies is social connection. People are connected into a community, that is the number one factor. The second biggest factor is probably diet, calorie restriction. Not overeating is associated with longer lives pretty much across the board. They also did a study on-
Dr. Robert Rountree:
And that's eating less, that's not starving yourself.
Dr. Nathan Price:
Yeah. Well, it's calorie restriction.
Dr. Robert Rountree:
Yeah. But doesn't have to be extreme.
Dr. Nathan Price:
Yeah. Exactly.
Dr. Robert Rountree:
Like Roy Walford.
Dr. Nathan Price:
Well, the quip on that, obviously, is if you do calorie restriction, either you'll live a lot longer or it will feel like it. So there's definitely trade-offs. Longevity is not the end all be all. But Calorie restriction is associated with it. The other elements, though, that come into play, when you study centenarians, two big factors that come up, which are not so obvious connected to lifestyle, are one, they have stem cells that appear to be younger. So they have more regenerative capability. And there's a lot of interest in that. Altos Labs was the biggest startup in history. They're starting with $3 billion. The best funded startup in history, which is about cellular regeneration, which is really fascinating.
Dr. Nathan Price:
And then the other element was that they have long telomeres. There's a lot of debate about how much you can do about those or if they're modifiable or how predictive they are. But in the really long live, they do tend to have these longer telomeres, which are the ends of your DNA. It's kind of junk at the end of your DNA so that they can ... As it gets broken down, you're not hitting anything essential. So it gives you a little more buffer, but those are all things that are associated with the longest lived people.
Dr. Robert Rountree:
So that kind of segues into a question that comes up all the time. What about dietary supplements? The person asked this, what supplements can I take to live forever?
Dr. Nathan Price:
Yeah. I love this question-
Dr. Robert Rountree:
If you want to
Dr. Nathan Price:
And the optimism behind it. One, I will just do a slight aside on live forever, just because it is a little bit of a hobby topic for me. We are very interested, obviously, focus on biological age of how do you reduce aging? But I want to be very specific about what that means. So if you graph the likelihood in any given year that you will die or you will contract or die of some serious disease, as you get older, it just goes up. Every year, it's more and more likely. That's essentially what we mean by aging.
Dr. Nathan Price:
Now, I'll go back to my undergrad really quick, which was in engineering, and I remember I was fascinated by this, because in one of the early lectures, we were getting taught that light bulbs don't age, light bulbs have no aging. These are the old incandescent light bulbs. What's meant by that is that a light bulb is just as likely to burn out on the first day you put it in as it is on the thousand day. Because it's actually related to the surge of electrical power that has nothing to do with the filament wearing out from the electric flow. So that's stuck with me. So that's what it means to be no aging.
Dr. Nathan Price:
So one of the things I want to point out is that even if we were able to eliminate aging, which would have probably a bigger effect on human health than anything, it would be radically bigger than things like curing cancer, which would affect about two years of lifespan, if you did it. But the thing I do want to point out is that even if you eliminate aging, and you make that curve flat, you're still infinity away from being immortal or living forever. You hear a few of the aging researchers throwing out terms like that. That's a whole different thing. But basically, reducing that curve is something you can do. So what supplements are actually involved there?
Dr. Nathan Price:
So the other preamble I'll give to this is, there's basically a level of evidence that you can have around supplements and a level of evidence that you can't for a while. And that is for most of these supplements or all the supplements, we can't say today that they have an impact on human lifespan or health span, because it will take a long time to see that because we live a long-
Dr. Robert Rountree:
It'd 20-year study.
Dr. Nathan Price:
We'll know it in 20 years and we don't have that. So when we say there's evidence behind these, what's meant by that? And there's some interesting papers, basically, arguing exactly this point in the scientific literature. So what you can have is, one, that you know that they increase health span and/or lifespan across multiple animal systems. So we know that they do it in other systems. And then two, we have a mechanism of action. And you can do human trials that show that that same mechanism of action happens in humans. And three, you have safety trials, so you know that they're safe, that they are doing the same function that we see in the animals, and that we know that increase healthspan and lifespan in the animals. That's what you can have today. And that's basically the level of evidence that's possible. So I'll go through the things, but that's what they have.
Dr. Nathan Price:
So people should understand, if you're looking at these things, you're basically saying, is that enough evidence for you or not? I take a bunch of these, but I understand that that's the evidence. That's where it is. That's what you have today. So let's go through a few of those. So one major one is that you lose NAD+ as you get older. NAD+ can be boosted through supplementation, and we'll talk about those in just a minute. Boosting NAD+ has been shown to increase lifespan or health span across a number of different animal systems. It has been shown that it's safe. And so while the primary compound that's been used so far is nicotinamide riboside.
Dr. Nathan Price:
So nicotinamide riboside is a precursor, and it's a small molecule, and it can cross the membrane of the cell and come in. And it's been shown that if you take nicotinamide riboside you will increase NAD levels in your cell. So we know that it's past safety trials in humans, we know that it has the effects on healthspan and lifespan in animal models, so it hits all those buttons. There's also a lot of interest in NMN. NMN is not as extensively studied in humans. So it's a little bit behind on that standpoint. NMN is an interesting compound, certainly, and you can get a lot of the same benefits from NMN. And there is a whole debate around NR and NMN. In the cell, NMN is closer to NAD. So NR becomes NMN, becomes NAD. And if that were the end of the story, then you would think maybe NMN. But the flip side, though, is that NMN does not cross the cell membrane.
Dr. Robert Rountree:
To get it inside the cell.
Dr. Nathan Price:
It doesn't get inside the cell. So outside of the cell, NMN essentially has to be converted to NR to then go into the cell to then be converted back into NMN and so forth. But those are both in the same kind of family. The reason I gave is the reason that we've focused on NR. If data switches and whatever we think is the best, that's the one we'll do. But that's where it's at today. So other important supplements. So another one is Quercetin. Quercetin is really interesting because it has been shown in a number of papers to be an anti-senolytic. So senolytic is probably a term that a lot of people won't be familiar with. But what it means is as you get older, you accumulate the kind of zombie like quasi dead cells throughout your body. And you need to clear them. And Quercetin has been shown, especially when it's in combination with a drug called Dasatinib.
Dr. Nathan Price:
But basically, you can use Quercetin as a means for accelerating the clearance of senescence cells, and that's been shown in a number of studies. So Quercetin is another one of the big ones. Another compound that's really useful is called Berberine. So there's a lot of interest in a drug called Metformin, and Metformin and Berberine are analogs. They're very similar to each other. Metformin, it's actually fascinating because diabetics who take Metformin get cancer at lower rates than people who don't have diabetes. And that opened up the eyes of a lot of us, okay, what's going on there?
Dr. Robert Rountree:
If you got diabetes, you probably have a higher risk of cancer.
Dr. Nathan Price:
Yeah, exactly. Exactly.
Dr. Robert Rountree:
You take Metformin for your diabetes, and it goes lower than average.
Dr. Nathan Price:
It goes lower than average. Exactly. So there's a lot of people that think, well, maybe everyone should be doing this or a lot of ... And there is a really well-known researcher in the field, Nir Barzilai here in New York, who's running a trial on this called TAME. Now Berberine has essentially the same effect on metabolic markers that Metformin does. And it actually has a better effect on lipid markers than does Metformin. So Berberine is a natural product analog for Metformin, very similar, and by the same kind of reasoning is believed could have a major impact on healthspan and/or lifespan.
Dr. Nathan Price:
In our biological age studies, I'll just say that controlling glucose, which Berberine is really useful for was the number one effect on biological age. Diabetes increased by six years, that's the most of any of those. Those are all things that have ... Anyway, we could go on about a bunch of others. But those are all areas that could make or different supplements that could make a difference.
Dr. Robert Rountree:
I wish we could get some of the top anti-aging researchers like Nir Barzilai to take supplements a little bit more seriously, because I think the literature is there really deserves more study.
Dr. Nathan Price:
Yeah. and one thing I will say, I was a researcher in aging funded by the NIH, I was in this thing called the Longevity Consortium, it was the largest NIH investment in aging, I believe. What I'll say is a lot of leading researchers are, especially in aging, are quite open to supplements. I wondered that as I was first getting into this space, because I didn't come from a background in studying supplements. As I got into this space, and we've had some really good conversations with a lot of the leading researchers, and there is, there's a lot of interest in nicotinamide riboside, there's a lot of interest in Quercetin, there's a lot of interest in Berberine, and there are actually quite a lot of studies.
Dr. Nathan Price:
There does tend to be a default on long-term clinical trials a little bit towards drugs. Your win at the end is bigger, because they're ... If it's a proprietary drug, they're radically more expensive, which we could do a whole other topic, which maybe we'll get into at some point. [crosstalk 00:38:47] that could be another episode.
Dr. Robert Rountree:
Yeah. If you have a drug like rapamycin, then you can make a patented variant on it. I think there is one, Everolimus or something that is quite expensive.
Dr. Nathan Price:
Yeah. Absolutely.
Dr. Robert Rountree:
Well, I think that's all we have time for this week, Dr. Price. But thank you so much for coming on the podcast. If people want to know what you're up to, how do they find out about your work? How do they follow you? Do you have a website or a specific place they can go to know what your latest publications are?
Dr. Nathan Price:
Sure. So if you want, you can follow me on Twitter. It's @ISBNathanPrice on Twitter or on LinkedIn, I post quite a lot on LinkedIn, you can find me there. Or if there are other reasons to reach out directly, you can do so for that if it's relevant. But those are the channels that are probably the easiest for people to see.
Dr. Robert Rountree:
Terrific. Well, folks that was Dr. Nathan Price, the Chief Scientific Officer at Thorne HealthTech talking about the hallmarks of aging and what you can do about it. As always, thank you everyone for listening and please tune in again. Thanks for listening to The Thorne Podcast. Make sure to never miss an episode by subscribing to the show on your podcast app of choice. If you've got a health or wellness question you'd like answered, simply follow our Instagram and shoot a message to @ThorneHealth. You can also learn more about the topics we discussed by visiting thorne.com and checking out the latest news, videos and stories on Thorne's Take 5 Daily blog. Once again, thanks for tuning in, and don't forget to join us next time for another episode of The Thorne Podcast.
Dr. Robert Rountree:
This is The Thorne Podcast, the show that navigates the complex world of wellness and explores the latest science behind diet, supplements and lifestyle approaches to good health. I'm Dr. Robert Rountree, Chief Medical Adviser at Thorne and functional medicine doctor. As a reminder, the recommendations made in this podcast are the recommendations of the individuals who express them and not the recommendations of Thorne. Statements in this podcast have not been evaluated by the Food and Drug Administration. Any products mentioned are not intended to diagnose, treat, cure or prevent any disease.
Dr. Robert Rountree:
Hi, everyone, and welcome back to The Thorne Podcast. Joining me this week is Dr. Nathan Price, the Chief Scientific Officer at Thorne HealthTech, the CEO of Onegevity prior to its merger with Thorne, more on that later, and a researcher who is named one of the top 10 emerging leaders in health and medicine by the National Academy of Medicine. How're you doing, Nathan?
Dr. Nathan Price:
I'm doing great. Wonderful to be with you, Bob. I appreciate it.
Dr. Robert Rountree:
Yeah. I'm really looking forward to actually having a little time to chat. I'm wondering if you can tell people who the heck you are. I know we could talk about your resume for a couple of hours. But maybe you could just give people a little bit of an overview and then tell us kind of how you got involved with Thorne.
Dr. Nathan Price:
Yeah, happy to. So I'm a scientist and I try to be an entrepreneurial scientist. I'm very interested at the interface of what can we learn and how do we translate it to society. And that's a long time interest of mine. In fact, the quote of mine in my high school yearbook is, "What I want to do in the future is invent something and start a company." I've always been interested in science and business for a long time. And so it's kind of interesting from that perspective. So in terms of my background, I have a PhD in bioengineering, which I did on building what are called genome-scale metabolic models, big computer models of how do you take nutrients that you take into your body and how to do all those biochemical processes work to create you. So that's been a long term interest of mine.
Dr. Nathan Price:
I was Professor and Associate Director of the Institute for Systems Biology for about a decade. In the last few years, I was there, I had a really interesting opportunity. Lee hood, who had been my mentor as a postdoc, and then I had gone back to ISP after a stint, as an assistant professor at the University of Illinois in Urbana, basically, came to with the proposition of merging our lab groups together. We had become both very interested in this area that we call scientific wellness or you could call it precision health. We'll talk a lot more about that. And so we ran a joint lab, The Hood-Price Lab for Systems Biomedicine there. Started a company at that time. We co-founded a company called Arivale together.
Dr. Nathan Price:
And through those efforts, we analyzed huge datasets on about 5,000 people where we had genomes and microbiomes, and metabolomes, and proteomes, and information about what people were doing in their health, working with health coaches up to on a weekly basis, at least monthly. And so we had this wealth of data, and I got really interested in not just what do you do after disease, we had a whole bunch of papers, 100 papers may be in systems medicine. But got much more interested in how do we stop disease before it starts? And what signals are there in the body that tell us that something is going to happen? How far can we push that? And so I became very interested in that as a topic.
Dr. Nathan Price:
About a year and a half ago, I got a call from Paul Jacobson, who's the CEO of Thorne with an interesting proposition, which was to come on, become ultimately the CEO of Onegevity. But really, to fold all of this together, and I still remember what he said to me. He just said when he reached out ... I'll just share this because I was planning to say no to him. I was very happy. I had this great job. We were doing this. I was very excited about what Thorne was doing. We had done a little bit in terms of a joint venture, but I had a million things to go. I was going about to say we're doing all these studies, we've got in the process of starting three different companies, and we're going to do 12 clinical trials. I just had this whole litany of things that I was going to go through.
Dr. Nathan Price:
Paul kind of short-circuited me right off the bat and said, he said, "You know what the problem with all you academics," says, "you want to have your hands in a million different things and you can't see the one huge opportunity that is staring you in the face." And he said, "If you really want to take all these things you're doing in scientists wellness, all this science that you're doing, and you want to make it really have impact in the world," says, "you've got to tie this all up into one thing." He says, "You come," he says, "I'll run business and you do science, and we'll build the greatest healthy aging company in the history of the world." I walked away from the call and I thought, I should probably listen to this and think about it. So that's how I got involved with Thorne.
Dr. Robert Rountree:
Well, fortunate for us. It seems like the whole team that Paul Jacobson has put together is pretty amazing. I think you'd agree with that.
Dr. Nathan Price:
Absolutely. So many great people that have been engaged. I feel like I'm still meeting amazing people across all the different buckets that go into Thorne HealthTech, which I guess we'll talk about a little bit more.
Dr. Robert Rountree:
Sure.
Dr. Nathan Price:
Yeah. It's an incredible team across many, many different areas, for sure.
Dr. Robert Rountree:
So it seems like this interest in preventive medicine, and really, it's advanced preventive medicine. In the mainstream when they talk about preventive medicine, they're basically talking about mammograms and colonoscopies and things like that, which is not really what you're getting at. You're getting at being able to pick up on early signs that something is wrong.
Dr. Nathan Price:
Right.
Dr. Robert Rountree:
Correct with that?
Dr. Nathan Price:
Yes. Exactly. And it's really about having a different focus. Because if we think about health care in the world ... A lot of people say this, so this has become kind of a common phrase, but it's true, which is that healthcare today is really disease care. Most of medicine today is wait until you have a significant problem, and then diagnose a drug and give it. In fact, I don't need to belabor this point, we all have ourselves or friends or so forth, who have literally gone into the doctor, explain what they're starting to have an issue with, and been told come back when the symptoms are really serious so I can prescribe the drug. So the whole notion of ... Lee Hood and I are actually writing a book on this. It will come out next year. Actually, it's written, it's just in review now.
Dr. Robert Rountree:
Great.
Dr. Nathan Price:
But essentially, is about how do we have a wellness-centric view where our whole mindset is not I'm going to wait till I have some serious problem and where I can justify the side effects of the drug, but rather, how do I improve, enhance, extend health span? How do I stay healthy for longer? Vibrant and energetic and all those kinds of things. And how do we do that in a sense that we have a focus on health that is proactive at looking at initially small deviations that can probably be corrected easily, rather than waiting until we have significant deficiencies that are very hard, if not impossible to put back together.
Dr. Robert Rountree:
You mentioned a word that I want to key in on for our listeners, which was health span. I'm wondering, since we want to focus during this particular segment on healthy aging, maybe you can distinguish health span versus lifespan and why researchers, scientists think that that's an important distinction.
Dr. Nathan Price:
So lifespan is pretty obvious, right? How long do you stay alive? There's a lot of debate in the scientific community about whether or not lifespan can be pushed out a lot?
Dr. Robert Rountree:
Can we be 150, live to be 150?
Dr. Nathan Price:
Can we be 150? Can we be 300? Those kind of things. And we all laugh because no one has made it that far, so far, as far as we know.
Dr. Robert Rountree:
Unless you're a turtle or certain sharks, I guess.
Dr. Nathan Price:
Yeah. But turtle ... And so they're all these tantalizing examples where we can extend lifespan in animal models, and sometimes pretty significantly. So there's all kinds of ... Anyway, without getting all into that there are questions about that. But what's ultimately what you could do in lifespan? Now, the flip side is if you talk to someone about even extending lifespan, a lot of people will say, I don't want that.
Dr. Robert Rountree:
Exactly.
Dr. Nathan Price:
Why? It's because you have this model in your head, I'm going to get old and frail, my mind's going to go. I don't want to drag out for years. And actually, I'm very much in that camp. Who would want? And we could get into all that, right?
Dr. Robert Rountree:
Yeah.
Dr. Nathan Price:
But healthspan is something that is, I think, hard to be controversial. It is what is the length of time that you have a healthy, enjoyable, vibrant life. And we know for a fact that you can extend healthspan significantly, and you can do so through very simple things. Exercise, extend your health span massively, good diet extends it. There are different compounds, which I'm sure we'll talk about, that have been shown to extend healthspan and animal models and so forth. And so it's really about just how do you take that health that is the cornerstone for a good life, and how do you make that last as long as you can?
Dr. Robert Rountree:
So this kind of brings up the million dollar question which is, is healthspan mainly a result of what we do, or is there an underlying program in our cells that affects aging that's more important? Or are we kind of stuck with our genes? Or what about lifestyle? What does nature and nurture have to do with the whole process?
Dr. Nathan Price:
Yeah. It's definitely a combination of both. But healthspan for most people is very modifiable. And so for the majority of us lifestyle is going to be the bigger component. But they do have interesting interplay. For example, a study that we did a few years ago, we published this in Scientific Reports in 2019, showed that we were looking at people who were going through a wellness program, so trying to get better, was the one we used to run. And as they were doing that, we actually looked at genetic signatures, in this case for whether or not a person was likely to have high LDL cholesterol, the so-called bad cholesterol, or HDL cholesterol, so-called good cholesterol.
Dr. Nathan Price:
And it turned out that if we monitored people going through a lifestyle program, and whether or not they were able to lower LDL cholesterol, the genetic signature predicted who would succeed at that and who would not. And the top 40% of people, so a big number, were not able or did not in our studies show a statistically significant ability to lower LDL cholesterol, where the bottom 40% did vary significantly. By top and bottom, what I'm talking about is you can actually build a prediction model off of the genome for the level of a biomarker associated with health. And then you can take the difference or the delta, I'm an engineer, so we call these deltas. But if you take this delta, it turns out that the difference between your actual measure and the genomic predictor is a big sign of whether that biomarker is easily movable or not.
Dr. Nathan Price:
And so what you can do, in fact, is build a plan or a guidepost for people that says, what are all the biomarkers associated with health, where you deviate the most from your genetic prediction. It tells you where you're having a big impact from lifestyle, and these are the things you're most likely to be able to change via lifestyle. And so there is this really interesting interplay. I actually think that the delta between your genomic prediction and your actual value is a whole new category that needs to be implemented across medicine, because right now, we take the measurements of somebody on all these standard clinical labs, in the absence of the genome. So we do not know, today, in 99% of practices, what if that high value is driven by the genome or by lifestyle? And it's hugely important in terms of how modifiable it is. Anyway, there's a lot around that, that's super fascinating.
Dr. Robert Rountree:
What about something like blood sugar? I bring that up, because some people will assert that the genes that are involved in insulin signaling and how your body handles blood sugar are the most important ones to consider when it comes to aging. Alzheimer's is diabetes of the brain, that kind of thing. And animals or even worms that have genes that allow them to handle glucose better, live longer. So would what you saying apply to that?
Dr. Nathan Price:
Yeah. I'll give you two pieces of evidence sort of on each side because, again, it comes down to the kind of the fraction of impact. So your genes definitely do matter and they'll matter a lot, certainly, for certain biomarkers you might find. So if you look at something like hemoglobin A1C, which is a, for our listeners, is a marker that's commonly used for diabetes. It looks at the glycation or the small sugar that get put on the outside of the protein.
Dr. Robert Rountree:
It's your average blood sugar over time.
Dr. Nathan Price:
Your average blood sugar over time, basically. But there are genetics that are associated with residence time of red blood cells. So how long in your body? So some people they're going to last about 120 days, some people that might be longer, 130, 140. And so the longer that they have residence time, the more time they have to accumulate like oscillations. We're actually in a clinical trial on this. So the way you interpret that measure is, again, influenced by something in the genetics, which again, is not done today. So there are all kinds of things that you can look at that way. Now, the counter argument to genetics being the primary driver of sugar issues is that we are experiencing a epidemic of things like diabetes and obesity, and the human populations genome didn't radically change over the [inaudible 00:15:03].
Dr. Robert Rountree:
We don't have new genes.
Dr. Nathan Price:
We don't have new genes. We have new environment and the environment has caused an epidemic. So the argument against genes being the whole story is pretty strong. So it's not the whole story. It plays a role. There's no doubt about that. But it's really the gene by environment interaction that is kind always the answer. It sits somewhere in there. It's just a fraction which one is stronger?
Dr. Robert Rountree:
Well, you and I have already talked about this offline. But there's a lot of excitement these days about these epigenetic clocks that tell you, supposedly, what your real age is, as opposed to the age that you might determine by measuring your blood sugar or your weight or your blood pressure, or things like that. And it seems like the problem that you and I were talking about with these epigenetic clocks is they don't necessarily reflect how you're living. They seem to be a whole independent phenomenon.
Dr. Nathan Price:
Yeah, it's really fascinating. So the epigenetic clocks, a lot of people are interested in them. They were discovered initially and a lot of work has been led by Steve Horvath, a terrific scientist down at UCLA who I've known for a while. So these epigenetic clocks are fascinating. And so I'm a big fan of them from the standpoint of what we might be able to learn as we go down that route. We do have a biological age test at Thorne, as you know, and we don't base it on epigenetics, we base it on a set of clinical markers. The reason we do that, and there's actually papers published, including by Steve Horvath and another just very top aging researcher, Morgan Levine at Yale, know that go into this and do a comparison.
Dr. Nathan Price:
The biological age from clinical labs today is more associated with health outcomes, with incidence of disease, and so forth, then our biological age is based on epigenetics. So we use those because they're more predictive of health outcome today. Because they've been studied for so long, every one of them gives us very specific actionable items of something we can do that we don't yet have around epigenetics. So I love epigenetics from a science point of view. I think it's fascinating. People want to do a test on it, go for it, I think, great. But we like primarily the clinical lab test just because it's more health actionable, more predictive of health today.
Dr. Robert Rountree:
I just want to point something out about the biological age test that Thorne offers, which is the first time I looked at it, I thought, well, this is what I'm already measuring in clinical practice, a chemistry profile, blood sugar, things like that, that seem fairly basic. And then I talked to you about how you arrived at that, and it turns out, you arrived at that from computing huge amounts of data. So it wasn't like you just said, hey, I think a chemistry profile would be a good thing. This was what you came up with after looking at thousands of patients.
Dr. Nathan Price:
Yeah. We initially did this study on about 3,500 individuals, and we measured 1,200 different analytes out of the out of the blood. And you can derive biological age on a wide variety of different sources. And you do get a bit of a different answer, depending on the one that you do. And you're getting different information. So we looked at metabolites, we looked at proteins, we looked at clinical labs, the ones we ended up going with. And so we did go in there and we were able to show that even when we reduced down to this set, I think, ultimately of 36 different markers, that we could keep 90, 95% of the information that we got from the 1,200 in terms of being able to predict health outcomes, which is what we really cared about in terms of its relationship to disease, and also whether or not if you were taking action that would improve your health, you would see it go down.
Dr. Nathan Price:
When we did that initial study, what we saw was that over the course of the years we ran that study, and we ran it ... People came in and out at different times. So it was a total of four years, but each individual length was different into there. But what we saw was that we saw an improvement in biological age of 1.16 years per year in the program. By improvement, I mean, the difference between the biological age and the chronologic age. The way we develop the test, this is also important, it uses something called the Chimera de ball algorithm. And I won't go into the details of that, but it has one important property, which is that it forces the algorithm to learn a biological age such that the expectation is that on average people will go up by one year per year. And so reason that that is really important is that it gives you a measure that you can look at longitudinally. You can monitor year over year.
Dr. Nathan Price:
So when we did that, we saw that women did particularly well. They were getting better at a rate of one and a half years per year during the years on that program. Men were getting better at 0.8 years per year, meaning they were aging 0.2 years per year by the biological age. Women were actually doing better. They were getting a little bit biologically younger, according to the clock. And so when we look at those kind of things, that gave us some confidence in the test, because we saw that positive delta ages, so your biological age being higher than your chronological age was associated with diseases, higher incidence of disease, and people going through trying to improve their health were able to improve this score.
Dr. Nathan Price:
Now, you can't improve it forever, and the lower your biological age is compared to your chronologic age, the harder it is to keep pushing it down. You can't push it down forever. But you can have a positive impact on it and you can watch it. And so even though we now use the pretty standard clinical labs with a couple of extra things in there like DHEA, which gives us a view into hormone health, those are run through a very different kind of algorithm. So it focuses more on where are you were at compared to where you might want to be for your age and your sex and those kind of things.
Dr. Robert Rountree:
I think this is a fabulous information. Just to point the obvious, we know that if you get a roomful of people who are all the exact same chronological age, you see huge differences, right? Some people look like they're 60, some people look like they're 50, some people look like they're 70. So there's clearly huge differences from person to person in terms of what's really going on. And that's what we call biological age, which is What's the age of your body, your organs, your tissues, as opposed to your date of birth?
Dr. Nathan Price:
Exactly.
Dr. Robert Rountree:
And I think what you're saying, from being able to look at the simple markers, instead of 1,200, you used 30 ... Did you say 35, 36 markers? And then you can tell people to do these basic things, to exercise more, lower their blood sugar, take care of their liver, really basic things, and that changes their biological age. So we can't change their chronological age, but we can decrease, at least, the rate at which they're aging biologically. And that's profound.
Dr. Nathan Price:
Absolutely.
Dr. Robert Rountree:
That's profound.
Dr. Nathan Price:
And one of the things I love about biological age is that it is an example of what we call a metric for wellness. So we would like to have tests that aren't just do I have this disease? Do I not have this disease? Want our tests where you can focus on getting a better score, an improvement in health. And so this is a kind of a first version of that. But I love the notion of having a sense in your body, are you clearing senescence cell well? [inaudible 00:23:00] the big hallmarks of aging? Are you dealing well with oxidative stress, which is another big element? Is your immune system on high alert all the time or do you have chronic inflammation? Et cetera, et cetera. And so having just insight on all those different processes and what you can do, either through lifestyle recommendations, or when appropriate, targeted interventions of the kind that we might do from Thorne. And so there's a whole host of steps that you can take to just look at where you're at, what's going right, and where could you use some benefit.
Dr. Robert Rountree:
Wonderful. Well, let's take a short break. When we come back, we'll answer some questions that have come in from the community. So I think we can get a little bit more specific about where we go with all this information. Although getting older is inevitable, you can control how well you age and Thorne offers a variety of solutions to help you do just that. Thorne's biological age test utilizes a blood panel that analyzes the rate of aging for your entire body and its various organs and provides specific recommendations to help you slow or improve the aging process.
Dr. Robert Rountree:
Thorne also offers several science-backed formulas that promote healthy aging from nutrient-rich NAD+ Boosters to collagen powders, so you can age better inside and out. Find the right formula for you by taking Thorne's healthy aging quiz and get real recommendation from Thorne's medical team. Learn more by visiting thorne.com/healthyaging. That's T-H-O-R-N-E.com/healthyaging. And we're back. So now it's time to answer questions that have come in from our community. The first question that has come in is from a listener who asked, Why did Onegevity merge with Thorne? So Nathan, I'll turn that over to you. Why two companies becoming one?
Dr. Nathan Price:
Yeah. So it really came down to what our goals are with Thorne HealthTech. What we're trying to do is to build a integrated deep solution for healthy aging. And so Onegevity as an AI platform, and the knowledge that we were building there just made a lot more sense when you put all the pieces together. So as we're working at Thorne HealthTech, trying to have this big integrated solution, we have 300 different products. But it's not just about what they are, it's about what is the health intelligence that's necessary to deploy them in the right way, the right person at the right time? And that's where Onegevity fits in. We also have another company that we bought into this called Drawbridge, which will deliver at home, blood measurement devices, and so forth. So there's all these pieces that we're putting together to form this cohesive, unified approach to trying to give people the best possible data, information and solutions and healthy aging and those things needed to be rolled together.
Dr. Robert Rountree:
In other words, it's not just about supplements anymore. It's the whole deal.
Dr. Nathan Price:
That's right. And that was really what Thorne HealthTech was about, which is Thorne is, obviously, an amazing brand, probably the highest quality supplement maker in the country. But that's not the ultimate goal of what we're doing. The goal is to extend healthspan and to do that in deep ways, and that's what the mergers are all about.
Dr. Robert Rountree:
So back to the aging topic, who are the oldest people, the centenarians and above? And is there anything that they do that they have in common? I always hear these jokes about the woman who gets up and has a cigar and whiskey for breakfast every day and live to be 115.
Dr. Nathan Price:
Absolutely exist.
Dr. Robert Rountree:
It totally exists. But are there their habits that they found in the research that are going to help you live that long?
Dr. Nathan Price:
There are. And if you're going to be one of those really oldest people, you probably have to both win the genetic lottery and the lifestyle-
Dr. Robert Rountree:
And the lifestyle thing.
Dr. Nathan Price:
But there are commonalities. The biggest factor that influences longevity, and it's quite interesting, but it's been reproduced in a number of different studies is social connection. People are connected into a community, that is the number one factor. The second biggest factor is probably diet, calorie restriction. Not overeating is associated with longer lives pretty much across the board. They also did a study on-
Dr. Robert Rountree:
And that's eating less, that's not starving yourself.
Dr. Nathan Price:
Yeah. Well, it's calorie restriction.
Dr. Robert Rountree:
Yeah. But doesn't have to be extreme.
Dr. Nathan Price:
Yeah. Exactly.
Dr. Robert Rountree:
Like Roy Walford.
Dr. Nathan Price:
Well, the quip on that, obviously, is if you do calorie restriction, either you'll live a lot longer or it will feel like it. So there's definitely trade-offs. Longevity is not the end all be all. But Calorie restriction is associated with it. The other elements, though, that come into play, when you study centenarians, two big factors that come up, which are not so obvious connected to lifestyle, are one, they have stem cells that appear to be younger. So they have more regenerative capability. And there's a lot of interest in that. Altos Labs was the biggest startup in history. They're starting with $3 billion. The best funded startup in history, which is about cellular regeneration, which is really fascinating.
Dr. Nathan Price:
And then the other element was that they have long telomeres. There's a lot of debate about how much you can do about those or if they're modifiable or how predictive they are. But in the really long live, they do tend to have these longer telomeres, which are the ends of your DNA. It's kind of junk at the end of your DNA so that they can ... As it gets broken down, you're not hitting anything essential. So it gives you a little more buffer, but those are all things that are associated with the longest lived people.
Dr. Robert Rountree:
So that kind of segues into a question that comes up all the time. What about dietary supplements? The person asked this, what supplements can I take to live forever?
Dr. Nathan Price:
Yeah. I love this question-
Dr. Robert Rountree:
If you want to
Dr. Nathan Price:
And the optimism behind it. One, I will just do a slight aside on live forever, just because it is a little bit of a hobby topic for me. We are very interested, obviously, focus on biological age of how do you reduce aging? But I want to be very specific about what that means. So if you graph the likelihood in any given year that you will die or you will contract or die of some serious disease, as you get older, it just goes up. Every year, it's more and more likely. That's essentially what we mean by aging.
Dr. Nathan Price:
Now, I'll go back to my undergrad really quick, which was in engineering, and I remember I was fascinated by this, because in one of the early lectures, we were getting taught that light bulbs don't age, light bulbs have no aging. These are the old incandescent light bulbs. What's meant by that is that a light bulb is just as likely to burn out on the first day you put it in as it is on the thousand day. Because it's actually related to the surge of electrical power that has nothing to do with the filament wearing out from the electric flow. So that's stuck with me. So that's what it means to be no aging.
Dr. Nathan Price:
So one of the things I want to point out is that even if we were able to eliminate aging, which would have probably a bigger effect on human health than anything, it would be radically bigger than things like curing cancer, which would affect about two years of lifespan, if you did it. But the thing I do want to point out is that even if you eliminate aging, and you make that curve flat, you're still infinity away from being immortal or living forever. You hear a few of the aging researchers throwing out terms like that. That's a whole different thing. But basically, reducing that curve is something you can do. So what supplements are actually involved there?
Dr. Nathan Price:
So the other preamble I'll give to this is, there's basically a level of evidence that you can have around supplements and a level of evidence that you can't for a while. And that is for most of these supplements or all the supplements, we can't say today that they have an impact on human lifespan or health span, because it will take a long time to see that because we live a long-
Dr. Robert Rountree:
It'd 20-year study.
Dr. Nathan Price:
We'll know it in 20 years and we don't have that. So when we say there's evidence behind these, what's meant by that? And there's some interesting papers, basically, arguing exactly this point in the scientific literature. So what you can have is, one, that you know that they increase health span and/or lifespan across multiple animal systems. So we know that they do it in other systems. And then two, we have a mechanism of action. And you can do human trials that show that that same mechanism of action happens in humans. And three, you have safety trials, so you know that they're safe, that they are doing the same function that we see in the animals, and that we know that increase healthspan and lifespan in the animals. That's what you can have today. And that's basically the level of evidence that's possible. So I'll go through the things, but that's what they have.
Dr. Nathan Price:
So people should understand, if you're looking at these things, you're basically saying, is that enough evidence for you or not? I take a bunch of these, but I understand that that's the evidence. That's where it is. That's what you have today. So let's go through a few of those. So one major one is that you lose NAD+ as you get older. NAD+ can be boosted through supplementation, and we'll talk about those in just a minute. Boosting NAD+ has been shown to increase lifespan or health span across a number of different animal systems. It has been shown that it's safe. And so while the primary compound that's been used so far is nicotinamide riboside.
Dr. Nathan Price:
So nicotinamide riboside is a precursor, and it's a small molecule, and it can cross the membrane of the cell and come in. And it's been shown that if you take nicotinamide riboside you will increase NAD levels in your cell. So we know that it's past safety trials in humans, we know that it has the effects on healthspan and lifespan in animal models, so it hits all those buttons. There's also a lot of interest in NMN. NMN is not as extensively studied in humans. So it's a little bit behind on that standpoint. NMN is an interesting compound, certainly, and you can get a lot of the same benefits from NMN. And there is a whole debate around NR and NMN. In the cell, NMN is closer to NAD. So NR becomes NMN, becomes NAD. And if that were the end of the story, then you would think maybe NMN. But the flip side, though, is that NMN does not cross the cell membrane.
Dr. Robert Rountree:
To get it inside the cell.
Dr. Nathan Price:
It doesn't get inside the cell. So outside of the cell, NMN essentially has to be converted to NR to then go into the cell to then be converted back into NMN and so forth. But those are both in the same kind of family. The reason I gave is the reason that we've focused on NR. If data switches and whatever we think is the best, that's the one we'll do. But that's where it's at today. So other important supplements. So another one is Quercetin. Quercetin is really interesting because it has been shown in a number of papers to be an anti-senolytic. So senolytic is probably a term that a lot of people won't be familiar with. But what it means is as you get older, you accumulate the kind of zombie like quasi dead cells throughout your body. And you need to clear them. And Quercetin has been shown, especially when it's in combination with a drug called Dasatinib.
Dr. Nathan Price:
But basically, you can use Quercetin as a means for accelerating the clearance of senescence cells, and that's been shown in a number of studies. So Quercetin is another one of the big ones. Another compound that's really useful is called Berberine. So there's a lot of interest in a drug called Metformin, and Metformin and Berberine are analogs. They're very similar to each other. Metformin, it's actually fascinating because diabetics who take Metformin get cancer at lower rates than people who don't have diabetes. And that opened up the eyes of a lot of us, okay, what's going on there?
Dr. Robert Rountree:
If you got diabetes, you probably have a higher risk of cancer.
Dr. Nathan Price:
Yeah, exactly. Exactly.
Dr. Robert Rountree:
You take Metformin for your diabetes, and it goes lower than average.
Dr. Nathan Price:
It goes lower than average. Exactly. So there's a lot of people that think, well, maybe everyone should be doing this or a lot of ... And there is a really well-known researcher in the field, Nir Barzilai here in New York, who's running a trial on this called TAME. Now Berberine has essentially the same effect on metabolic markers that Metformin does. And it actually has a better effect on lipid markers than does Metformin. So Berberine is a natural product analog for Metformin, very similar, and by the same kind of reasoning is believed could have a major impact on healthspan and/or lifespan.
Dr. Nathan Price:
In our biological age studies, I'll just say that controlling glucose, which Berberine is really useful for was the number one effect on biological age. Diabetes increased by six years, that's the most of any of those. Those are all things that have ... Anyway, we could go on about a bunch of others. But those are all areas that could make or different supplements that could make a difference.
Dr. Robert Rountree:
I wish we could get some of the top anti-aging researchers like Nir Barzilai to take supplements a little bit more seriously, because I think the literature is there really deserves more study.
Dr. Nathan Price:
Yeah. and one thing I will say, I was a researcher in aging funded by the NIH, I was in this thing called the Longevity Consortium, it was the largest NIH investment in aging, I believe. What I'll say is a lot of leading researchers are, especially in aging, are quite open to supplements. I wondered that as I was first getting into this space, because I didn't come from a background in studying supplements. As I got into this space, and we've had some really good conversations with a lot of the leading researchers, and there is, there's a lot of interest in nicotinamide riboside, there's a lot of interest in Quercetin, there's a lot of interest in Berberine, and there are actually quite a lot of studies.
Dr. Nathan Price:
There does tend to be a default on long-term clinical trials a little bit towards drugs. Your win at the end is bigger, because they're ... If it's a proprietary drug, they're radically more expensive, which we could do a whole other topic, which maybe we'll get into at some point. [crosstalk 00:38:47] that could be another episode.
Dr. Robert Rountree:
Yeah. If you have a drug like rapamycin, then you can make a patented variant on it. I think there is one, Everolimus or something that is quite expensive.
Dr. Nathan Price:
Yeah. Absolutely.
Dr. Robert Rountree:
Well, I think that's all we have time for this week, Dr. Price. But thank you so much for coming on the podcast. If people want to know what you're up to, how do they find out about your work? How do they follow you? Do you have a website or a specific place they can go to know what your latest publications are?
Dr. Nathan Price:
Sure. So if you want, you can follow me on Twitter. It's @ISBNathanPrice on Twitter or on LinkedIn, I post quite a lot on LinkedIn, you can find me there. Or if there are other reasons to reach out directly, you can do so for that if it's relevant. But those are the channels that are probably the easiest for people to see.
Dr. Robert Rountree:
Terrific. Well, folks that was Dr. Nathan Price, the Chief Scientific Officer at Thorne HealthTech talking about the hallmarks of aging and what you can do about it. As always, thank you everyone for listening and please tune in again. Thanks for listening to The Thorne Podcast. Make sure to never miss an episode by subscribing to the show on your podcast app of choice. If you've got a health or wellness question you'd like answered, simply follow our Instagram and shoot a message to @ThorneHealth. You can also learn more about the topics we discussed by visiting thorne.com and checking out the latest news, videos and stories on Thorne's Take 5 Daily blog. Once again, thanks for tuning in, and don't forget to join us next time for another episode of The Thorne Podcast.
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