The SECRET To Longevity & Never Getting Old IS COMING... | Peter Diamandis & Mark Hyman

We're going to start to have new tools to slow stop and reverse aging.

I think, you know, muscle is the currency of aging. The idea that we have the software that kind of gets gummed up as we get older, but there are ways to sort of reset it through various strategies around longevity is really intriguing to me because, you know, when I look at the common age related diseases, they're all have common mechanisms, right? Inflammation, oxidative stress, changes in the microbiome that all impact that, hormonal dysregulation, mitochondrial dysfunction, and you sort of start to look at the root causes of all this, toxin overload and accumulation of all that. Those just seem to me to be the sort of low hanging fruit to kind of work on to affect the ravages of aging. And, a lot of the things that influence those are what we call the exposome, which is what are your genes exposed to? You're talking about how do we modify gene expression, epigenetics, you know, your exposome includes everything from the air you breathe, the water you drink, the thoughts you have, the altitude you're at, the microbiome is in your gut, to the food you're eating, the amount of exercise, the way you, whether you are loved or not loved. I mean, they're all things that are affecting these things in real time. So the question is in your research on longevity and in life force, what did you come up with that were the sort of the key anchors that people need to focus on to improve the quality of their health, to add more life to their years and more years to their life.

Well, because at the end of the.

Day, people listening like, what's in it for me? Like, how do I, you know?

So listen, no surprise, Mark, it's everything you've been teaching and talking about and writing about for quite some time. And you are definitely the guiding light.

I'm the loudest voice maybe, the most annoying voice.

So, you know, listen, I think it's very clear that First of all, people should have hope that there are incredible technologies in development right now and incredible therapeutics. I'm involved with a number of companies I've co-founded that are doing things we can talk about those. And your job is to live long enough to intercept all these technologies. And there are things you can do right now. And I think about them as the fundamentals. Number one, sleep eight hours. if the body could have evolved to do as well in less than eight hours, it would have. While we're sleeping, we are sitting ducks. And so, a species of hominids that could sleep for six hours and do as well would have out-competed everybody else who slept eight hours. So, for me, that's obvious. Number two, it's what you eat. Eliminate sugar. is first, you know, first second and third in the list and then a whole. Yes. You know, whole plants. It's the work that you and Dean Ornish talk about. So it's, I just try and do my best. I'm not a saint, but I just try and remove all sugar. The way I do it, I don't buy it at the supermarket. I just, if it's not in the house, I can't eat it. You know, when your willpower is a week, don't have it there.

That's what I always say. If there's chunky monkey in the freezer, I'm done. Like, I, if I have a bad day and there's a pint of chunky monkey, there's no holding me back. But if it's there. I'll just, I'll look, I'll feel depressed for a minute and then I'll go back to my room and read a book.

Exactly. 100%. You know, it's drinking two, three or more liters of water per day. It is exercise, you know, and you and I both are, you know, I try and get my 10,000 steps in every day and I try and do at least a light weight workout. I'm not going to to benching you record, but I'm using free weights to keep muscle tone. Muscle is one of the highest correlations with longevity.

Unbelievably great that you said that because I think muscle is the currency of aging. And as we age, we lose muscle. And muscle is where our metabolism is. When it's lost, we replace it with fat, which generates inflammation and oxidative stress. And tanks are good hormones. like testosterone and growth hormone and raises our bad hormones like cortisol, all of which accelerate aging. So, most people don't think about muscle as an organ. They don't think about how to preserve muscle, create muscle, create better efficient muscle, more highly functional muscle, more mitochondrial intelligence and function. Those are really to me some of the most important things with aging. And so, you know, there's really two aspects that I hear you talking about. One is sort of the basic foundational things we know about how to actually upgrade your life. and upgrade your biological software through lifestyle. And then there's all these really extraordinary techniques, which are gene editing techniques, which are using various sort of innovative compounds to affect some of these gene expression patterns to things that I don't even probably know about that you've uncovered that are being explored, whether it's things like NAD or whether it's things like, you know, things that help regulate the economic factors, whatever those are. There's a lot of that going on. So I think the basic stuff people have a pretty good handle on is sort of the obvious stuff.

Yeah, I mean, there's a couple of other things I just want to hit on. Mindset and attitude is probably one of the most important things. You know, it's, if you think you're gonna die, you can will yourself to death. Who do you hang out with, right? Are you hanging out with people at the very end of their life? Are you hanging out with people who are youthful? your mindset is so fundamentally important. And do you have a vision, is the vision for the years ahead of you bigger than the vision for the years behind you? You know, I mean, that's fundamental. Fundamental, right? I'm more excited to be alive now than I ever have. And the projects I have are going to keep me going for the next few hundred years. So I'm super pumped about that.

Yeah, no, you're right. You know, it's really true when you look at, meaning and purpose. It actually directly correlates with longevity. And optimists live longer, even if they're wrong. And I, I actually spent a lot of time this last week with a 99 year old man who is brilliant, still working. I said, so what are, what are you, what are your interests? He says, well, I'm interested in longevity. And he was 99 years old. He's telling about the projects he's working on, the movies, the film he's making, the I mean, it's just, it's really stunning to me to see someone that age be so engaged in life and joyful and committed to his friends and his community and his family active. I mean, I was like, wow, that is just really remarkable. You know, you probably know him, Norman Lear. He's just an amazing guy.

Oh, I love Norman Lear.

I'm just like, to be able to be that up close and personal with him and hear him talk about his life and his stories, but also talking about what he's dreaming about for the future. he's dreaming about the future. And that's pretty exciting to me.

There's another category of what you can do right now that's important. And I jokingly call it not dying from something stupid.

There you go.

But it's really important.

I call it how to die young as late as possible.

Okay. So here's the realization. All of us are optimists about our life, about what's going on inside our body. We think we're fine, we're great, moving along, we're rushing to work and to vacation and spending time with our families, and that's all awesome. But we actually have no idea what's going on inside our bodies until you end up with a pain in your side in the hospital and the doctor says, listen, I hate to tell you this, but whatever it is. And so this is the work that I had done early on in human longevity, and really we've taken it the next level with a platform called Fountain Life. We talk about Fountain Life in the book. But it's the notion that every year I go for a digital upload. I go to HLI, Human Longevity Inc, or Fountain Life, and I do a full body MRI. head to toe, brain, brain vasculature, a clearly coronary CTA that uses AI to look for soft plaque versus calcified plaque. Calcified plaque is safe. It's the soft plaque that can rupture that you have to worry about.

Yes, yes.

Dexa scan, my genome, my microbiome, my omics and so forth. And my goal is two things. Has anything changed in the last year I need to know about? And is there anything so first of all, it's given me a baseline of this is where my body is. Originally when I first did it, I saw I had a large aortic root where the aorta enters the heart. And it was like, is that dangerous? Should I be concerned? But then after doing it four or five times, it didn't change. That's just me. That's just normal for me. But, we have found in like 14, 15% of people who've come through it, and these are all relatively wealthy who can get any health care they want, who are typically in their 50s, 60s, 70s, two and a half percent have an aneurysm they didn't know about. Yeah. Two percent of cancer they didn't know about. And all in all, I think the number was like 14 or 15% have something that they need to know about that's going to impact their health. And so, that's my, you know, wear your seatbelt, get yourself uploaded every year. And if you find something, take action. People say, I don't want to know. And I call bullshit. Of course you want to know because you can do a lot about things right now.

Absolutely. I think what you're talking about is really important, Peter, because what you're talking about is a host of diagnostics that often are not something we would get in traditional doctors. Hopefully the prices are gonna come down so we can get them. But, you know, there's a lot of imaging, a lot of diagnostics that are great, but then there's a whole layer of things that doctors aren't looking at. And I see this all the time, you know, with people who are coming to see me for a functional medicine. There's subclinical changes that happen and you can detect changes in your biology and physiology decades before you ever get a symptom or before you get diagnosed with the disease, whether it's insulin resistance that you can see early on by raising, looking at insulin levels after a meal or fasting insulin, which is the first thing you go up way before your blood sugar goes up, or whether there's low-grade autoimmune disease, or whether your microbiome's off, or you have nutritional deficiencies or mitochondria aren't functioning. Exactly. We can start to see these things and it's really just like a tune up. They're not quite diseases yet. And then traditional medicine just hasn't had a way of thinking about this because it's really complex. And what's, I think emerging and what you're finding, Peter, is that there's this emerging field of omics revolution, which is, you know, when you think about the number of data points that we get when you go to the doctor, you get like 20, 30, 40, 50 lab tests maybe. there's literally tens of thousands, hundreds of thousands of things you can measure, most of which we're ignoring. You know, like, like David Fuhrman at Stanford has looked at the throughput analysis of literally thousands and thousands of molecules around inflammation, which are those ones that relate to aging and chronic disease. And they're things you've never heard of before. They're things your doctor never tests for, that aren't a lab requisition, but are the most important things that we can be measuring to look at long-term inflammation and aging. So I think there's a whole host of things that we can start to look at and from a functional medicine perspective, that's what excites me because I see these things and I can then see the changes that happen. I can see the changes in biology that happen. And, I've noticed in myself, I've literally kind of changed my biology and how I posted a picture recently of when I was 40 and when I was 60 in my body and it's totally different. I was sort of like skinny fat back then. I was eating more carbohydrates. I wasn't overweight, but I didn't really have much muscle. And, you know, look at me now, I look like 20 years younger, but I was 20 years younger than that picture than I am now. So it's like really quite, it's quite staggering what you can do when you begin to understand these things.

Yeah, and there are two reasons we haven't done this in the past, maybe three. One, we couldn't before. We couldn't measure it. We didn't even know it was there or measurable, but we now do. And second, it's getting cheaper and cheaper all the time. But the third is that no human physician could ever deal with the amount of data we're talking about. It's a massive amount of data. No. And it's really the use of machine learning algorithms that are helping us understand the patterns, understand what it means. I think it's going to become in the next five years malpractice not to do a diagnosis without AI in the loop just because.

Absolutely. No, I mean, it's like I've seen literally millions and millions of data points on tens of thousands of patients, but I'm one guy and I've seen patterns and correlations on things that no one has described before. And yet, I know are true because I see them over and over again, but nobody's really kind of described in the literature. And, I think that's just sort of the tip of the iceberg of what's really going on when we begin to look at these things. So, that's what's sort of exciting was we can look at the longevity perspective. We get to look at how do we start to do diagnostics differently, not looking for disease per se, but looking.

For sort of variations from optimal function and health. So, that's what we've done at Fountain Life. We have, you know, by the end of 2022, We'll have a dozen centers set up in Dubai, in India, in the UK, in Toronto, and about 10 in the US. We're doubling in the 2022 timeframe. And we basically digitize you and upload you into the system where we can understand what changes have occurred since last time. And that's part of what Fountain Life does. The other part is performance and recovery. It's how do we use, how do we actually, what are your goals? Is it muscle? Is it obesity? Is it, you know, energy levels? And we help direct you in our programs that way. But then there's a regenerative medicine side that is important because the regenerative medicine arena is growing tremendously. But we've built something called Fountain OS, which is an app that allows you to upload the data into your app, but it allows you to provision these things wherever you are. So if you don't live in the city where there's a fountain center, we have identified the imaging centers and facilities in Schenectady or in Des Moines, where you can get all of the tests put together and uploaded to the system. independent of where you live. And then the fun part is we have something called Fountain Health, which is life insurance, I'm sorry, health insurance business.

So.

You know, health insurance, it pays you after you have disease and after you get treatment. But what if instead health insurance was the opposite, which is we're going to provide you all of the imaging that Fountain Life does for free every year to catch disease at the very beginning and prevent it in the first place. So, it's insurance that's going to be for self-insured companies initially, but it's about giving all of your employees all of this extensive testing as part of the insurance package for free to prevent the disease in the long run. So, Fountain Life is doing great and super pumped about it.

So, it's basically these clinics where you can go and get a range of different assessments and therapies that assess where you are now, where you are in the deviations in your sort of longevity track, and how to actually change those back to a younger biological age using a combination of lifestyle, supportive therapies, functional medicine, regenerative therapies that are all out there now and be able to incorporate as in real time as new therapies come online. when we hit longevity escape velocity, we'll be able to actually all get to take advantage of that, which is pretty exciting.

Yeah, it is. We also have a very limited, we call our Edge program. So, as you all know, there's a lot of open investigational new drugs out there on the cutting edge, like rapamycin, like total plasma exchange, and so forth. So, we give a a small number of our Fountain Life members, the ability to participate in these research protocols.

We're seeing life expectancy go down, particularly in this last year of COVID where we saw it go down for the average person, probably one plus years. And if you're African-American, Hispanic is up to three years of decrease in life expectancy. And at the same time, we're seeing an explosion of longevity science that's helping us understand the causes of aging, how to extend life, how to improve quality of life, how to stop the ravages of aging. And we're learning all kinds of new tools, techniques, and technologies, but there's a big mismatch there. So can you talk about, you know, one, why we're seeing this increase.

In.

Earlier and earlier deaths or a decrease in life expectancy, and why at the same time we're so optimistic and hopeful about the future of longevity science?

Absolutely. And I think there's nothing that's more valuable to all of us and our families than healthy years. And let's define longevity in the first place. The average age of hominids back 100,000 years ago was probably in their late 20s. And then it expanded during the Middle Ages into the early 30s. And then 100 years ago, it was in your 40s. Today, it's in their late 70s. And I like to think about the fact that I don't believe humans were on the whole designed to live past age 30. We would have a baby by age 13 before there was birth control. I mean, seriously, you go in puberty and you have a baby. And by the time you were 27 or 28, your baby was having a baby. And before McDonald's and Whole Foods, before food was abundant, the worst thing you wanted to do to perpetuate the species was take food out of your grandchildren's mouths. And so that was very much reality for it's the what we evolved during. And then all the diseases of older age, cancer, heart disease, dementia, even when aneurysms take people, the wear and tear of the body, all of those diseases were never selected against if you didn't get it past age 30. So, we're in optimal health in our 20s and 30s. And then we start the ravages of old age. And what's interesting, and I think you know this as much or more than I, that the conversation around longevity and I'm going to define it more as age reversal, like how do we slow aging, stop aging, even reverse aging, which would have been a really crazy conversation to have had even five years ago, is now become the conversation du jour in the medical community and in the venture community. And there's more people thinking about and working on it. And so I think I personally believe, and hopefully at the end of this conversation, you'll believe or others will that we're about to go into a renaissance of health. We're about to massively disrupt the health industry, reinvent it, and start to add. Amen to that, right? Of course, you and I are both on carrying the signs around, you know, Vive la Revolution, let's reinvent this crazy insane system, which is so moribund. Anyway, but I think this decade we're going to start to have new tools to slow stop and reverse aging. And I'm convinced myself from the people I've spoken to, I don't know, when I was in medical school, I didn't get a chance to watch much TV, but I remember watching, I would watch Star Trek once in a while. That was sort of like my, if I had a little bit of time, I'd watch a Star Trek episode and that was like, The way the world should be.

-With the spy quarter, right?

-Yes, exactly. But I remember watching one television show on long-lived sea life, that species of bowhead whales could live 200 plus years, and the Greenland shark could live four or 500 years, and sea turtles could live equal. And I was like, if they can live that long, why can't we? I mean, I was really, I was kind of pissed and perplexed at the same time. And I made the decision it was either a hardware problem or a software problem. And that we were gonna start to understand, how do we change our software or how do we change our hardware? So that's the frame that I have. Yes, we've had some recent decreases and a lot of the increase, as you well know, in average, and the word average here is the key part, average life expectancy has been the massive reduction in childhood mortality. and the ability to deal with diseases early.

Clean water.

Clean water. Oh my God.

Sanitation.

Half the disease burden of the planet is due to unclean drinking water. It's crazy. Knock that domino over. So, I don't think the recent gains in longevity are really the kinds of gains in longevity that I'm It was.

The first hurdle we had to overcome, which was deal with the bad water and infectious disease. And, we did a good job at that. And now we're looking at the aging process. And, you know, as I began to look at it over the decades, it's really clear to me that what we most of us see as aging in this country is abnormal aging. It's biological processes that have gone awry that are really dysfunctional states of biology. And then if we learn how to work with biology to optimize those states, whether it's inflammation or oxidative stress or changes to the microbiome or hormones or brain chemistry or your structural system tissues, you can really stop and even reverse the phenomena that we see as aging in this country.

For sure. But even doing that, the question becomes, can we all get to 100 healthy? Can we get to 120 healthy? and what's beyond that, right? Yeah. And I'm working on both sides of the equation, a number of the companies I have and the work that I'm doing, this book that Tony and I have worked three years on, Life Force, is really around increasing your vitality, your energy, avoiding the ravages of obesity and diabetes and heart disease and so forth. And there's incredible new technologies on the horizon. We looked at all of the stuff in phase one, phase two, phase three clinical trials. And then there's the basics, diet, sleeping and exercise, which we so don't want to spend our time doing. But we must. So how do we take this a piece at a time? There's an interesting Let me start with a big exclamation point on something that was a big insight in writing this book. Yeah.

And the book is called Life Force. It's out now. You can get it anywhere you get books. It's a very thick tome, like War and Peace, but it's your life. If you want to put more life in your years and more years in your life, this is the book you should get.

Thank you. And it's written in a way that read section one and then and then you can cherry pick if you're focused on heart disease or dementia or, you know, inflammation or, you know, cancer. The go read the chapter on that. It's a look at all of the, everything that's been approved or what's in phase two, phase three clinical research that will be approved in the next few years. It's all really hard science in a very understandable fashion. The goal of this book is to give you hope for the future, to give you a roadmap of what you should be doing now and what you should be looking for, right? It's a roadmap for a longer, healthier life. I mean, I'm looking for myself, you know, and people may think it's insane, a multi-hundred year lifespan. But, you know, if I shoot for that and I get 120 or 150.

Well, I think you're going for the multi-hundreds. I was just going for 120. I feel like I'm kind of falling behind here, you know, kind of get with the program. Multi-hundreds, I didn't even think of that.

Listen, there's a couple of things to think about. First of all, there's a concept called longevity escape velocity, which you're familiar with Aubrey de Grey, Ray Kurzweil has spoken about this. And that the notion is that as science is beginning to understand why we age and why we don't have to, and as science is making more and more breakthroughs in underlying diseases. There is a moment in time where for every year that you're alive, science is extending your life for more than a year. And that moment in time is called longevity escape velocity. When I ask Ray Kurzweil, Ray is brilliant. He's passionate about this area. He's my co-founder at Singularity University. He wrote the Singularity is Near and and has written extensively about longevity. I said, so Ray, when do you expect we're going to hit longevity escape velocity? His answer was in the next 12 to 14 years.

Basically what you're saying is if you can survive 12 years, you can live forever? Is that the idea? That's a comment.

I'm not going to back that up. But then I went and spoke to George Church, and I said to George, and George is professor of genomics at Harvard Medical School. He's brilliant. one of the early people across gene therapy, CRISPR, he's created 24 companies in 24 months. We never bet against George. And I said, When do you expect we'll see longevity escape velocity? And he gave me the same answer. He said, Next 12 to 15 years. But that's crazy, right? So we'll come back to that in a moment. What are the implications?

So you think we can make it to our early 70s, Peter? You and I will be in our early 70s then.

I'm sure we'll be all right. I'm definitely shooting for it. Here's the realization that we have just in the last 10 years, and you know this so well, the unveiling of CRISPR and all the different modalities of CRISPR and of gene therapy and of.

Reading- Explain for people what CRISPR is, because I don't think people understand what that is.

So, you can think of our, we have 3.2 billion letters in our genome. it comes from our mother and 3.2 billion letters that comes from our father. And over the last 25 years from the Human Genome Program and Celera, we've developed the technology to read that genome, to actually read out what are the 3.2 billion letters that shape you. It's your genome. And reading your genome is useful. But what we've now done, and the technology called CRISPR, I won't accurately, it's an acronym for clustered repeats is the CR in here, but it's a technology derived from bacteria that were using this technology to protect themselves against bacteriophage, viruses infecting the bacteria. Long story short, it's a tool for being able to accurately edit your genome. So in the same way that word allows you to read a document of all of the letters and words, 3.2 billion letters in the book of your life, CRISPR is the way that you can actually edit it accurately. And so the ability to read your genome and edit your genome and write your genome, and then a new technology called gene therapy comes along, which is the ability to actually use a virus as a robot to inject into the cells you want a specific gene. So it's like being able to inject into the book of your life a paragraph where you want it to say something. Anyway, these are incredible tools that are giving us the ability to not accept what we're born with.

But to begin- if you have a single gene mutation like, let's say Huntington's chorea.

Or thalassemia, sickle cell anemia, right? Right.

You can actually edit those genes to actually change the proteins that are produced that change the course of that person's life.

And what's incredible is it's not a treatment for these genetic diseases, it is a cure. It is like one and done, you're cured. And so, Editas, a company started by George Church out of Boston, has a CRISPR treatment to cure a form of genetic blindness. And so, a person's born with this particular genetic mutation, they're blind, an injection in the back of the eye, and they can see again. They're cured. I mean, it's biblical in nature. It's incredible stuff. But it's interesting. So now the question is, if you have these 3.2 billion letters when you're born and when you have it when you're the same 3.2 billion letters at age 25, when you got all your musculature on the beach or you're in a bikini, you look great, you feel great, and then you have the same 3.2 billion letters when you're 80. Why don't you look the same?

That's a great question.

What is it? Why aren't you, I mean, I've got the same, I'm running the same computer code, why am I looking at this?

Why is the software output different?

Yeah, and so this is fascinating. This is the work that was best explained so far by Dr. David Sinclair also at a Harvard Medical School who wrote a book called Lifespan, which is amazing. I think Lifespan and Life Force are two books that will go hand in hand.

He must have something about aging because he's like 50 something and he looks like 12.

I tell you, I'm- I don't know.

What'S up with that. I love David.

He's my poster child. I'm running, he's the, you know when you're in a marathon and there's somebody that you're pacing yourself against, he's the guy that I'm like, I've gotta pace myself against David. He does, he looks like he's 30. And his, you know, you write in the book, in the chapter, we have all these heroes in the book, David Sinclair, we say, you know, David's got two numbers, he's 53 in chronological age, But his biological age by aging clocks is like 35 or something like that.

And he looks amazing. Well, I did mine. I did mine. I'm 62 and if you did a few years ago, but it was 39.

Amazing.

It's possible.

It is possible. Yeah, I'm tracking, I'm 60 and I'm tracking in my mid-late 40s. My goal is to get down to a David Sinclair level of my mid-30s. And then I feel like I'm 28, but I have the emotional maturity of a nine-year-old, but that's a different story.

I think you're good. You're curious, you're in wonder all the time, in awe, which is actually a trait you should never give up. I don't ever want to hear about you most, Peter.

Let's go back to the question of you have your same genome at birth at 25 and 80. What's going on? And so, it's a concept called the epigenome. Epi, meaning above in Greek, and it is, in fact, the way that your genome is controlled. What's going on at birth at age 25 and 80 plus, as you know, is not all your genes are turned on or all your genes are turned off. Your epigenome controls which genes are on and which genes are off. In your youth, you've got many more genes turned on to create the proteins in your skin. And as you get older, some of those genes turn off and they should be on, genes that are on that should be off, and genes that are off that should be on. And that is what's thought to account for the aging process. And so let's double click on that, 'cause there's a very interesting construct and rationale of why that occurs. and I find it one of the most, when I'm on the stage talking about aging, I want to convey this because it helps people understand what's going on. So it turns out that we have a set of seven genes, which are our sirtuin genes that generate the sirtuin proteins, and these sirtuins control which genes are on and which genes are off. It controls the epigenome, but these sirtuins also are responsible for DNA repair. And I want you to imagine that your 3.2 billion letters are the piano keys on the piano. And you're playing the piano. You're the sirtuins that are determining which keys should be played and which keys should not be played. and early in your life, you've got this thing on the side of you, like this clock you have to repair. And early in your life, the clock is doing fine and you're not distracted by repairing it. But as you get, as you're, as the Pianist, as you're, as you're continuing in life, you're playing the right keys, you're, you're pushing the right ones and not pushing the wrong ones. But as things go on, you have to repair this, this. clock more and more and you're being distracted. So you're trying to keep the clock repaired at the same time you're trying to play the right keys and it becomes more and more difficult. But then there's another part of this, which is that these sirtuin proteins are powered by NAD in your cells. And as you get older, your NAD levels, sort of a energy currency, if you would, in the cells, your energy levels drop by half. So, all of a sudden, as the pianist, you're spending more and more of your time repairing, doing repairs, and having less and less energy to do the whole thing and you become distracted and the epigenome regulation of your body falls apart. So, what David believes he has been able to demonstrate, and we talk about this in the chapter on on David Sinclair and another chapter I wrote on longevity, that he has discovered that using three out of the four Yamanaka factors allows him to reset the epigenome in the living cell.

It's a big mouthful. What's the Yamanaka factor?

Yeah, what's the Yamanaka factor? It's interesting. Can I get one on the kitchen counter?

Yeah.

So, a guy I, Dr. Yamanaka Nobel Laureate, discovered that you can take a differentiated cell, a skin cell, a nerve cell, a heart cell, a liver cell, whatever it is, and return it back to its pluripotent state. What does that mean? When we're born, we have like one cell, you know, like the fertilized egg, and that grows and grows and grows and eventually differentiates into all these different kinds of cells in your body, your skin cell, your bone, your muscle, your heart, your nerve, your liver, your kidney. And all those cells have the same genome, but again, it's which of those genes are turned on and which of those genes are turned off determine what kind of a cell it is, what its function is. And we've heard of stem cells and those stem cells have the ability to differentiate into any one of these specialized cells. Well, Yamanaka determined that these four factors, these four genes, proteins, if you utilize them, you can turn a differentiated cell back into a pluripotent stem cell that could then, you could take it from a skin cell to a pluripotent stem cell and then make it a heart cell or make it a nerve cell.

Wow. So you can reverse the process of the evolution of the cell into its final form into its pre-existing state.

Exactly. And we'll come back to this in a little bit on the work of Dean Kamen, who's manufacturing or backup set of organs for all of us, which is insane. Hold on for that one. So long story short, David Sinclair, working with three out of the four Yamanaka factors, was able to reverse the age and publish this in December of 2020 on the COVID of Nature, reverse the age of the vision system of long-lived mice. So these mice who had gone blind with a whole set of of age-related decapitation of their vision system, their optic nerve, he was able to bring them back to an earlier state where they were fully functional. It's since been done with the heart of mice. And so, the question is, can you reverse, can you get your body to go back to a state of, hey, this is what your body should look like. These are the genes that should be on and off when you're, you know, instead of 60 when you're at 40 or at 30. And it's, the concept is age reversal, which is extraordinary. You know, I'm working on Mark right now. And when we did our walk, if we talked about this, I'm working on a 100 million dollar age reversal X Prize. And- that's pretty exciting. Yeah, I've raised about three quarters of the capital for it. We launched $100 million gigaton carbon removal prize at Elon Funded. And this is the next big one I want to do. We get teams around the world working on how do you reverse aging. In this case, we'll ask them to do 20%, I mean 25%, 20 years in humans with a therapeutic that lasts less than a year. but there's serious conversations about this now. One of the things that are on the horizon from that sort of other.

Than the foundational lifestyle stuff, which is really all the stuff, you know, we've been talking about forever, but it actually really matters, you know, whether it's, you know, relationships and community and meaning and purpose and eating whole foods and extras, all those things obviously are important. And then, you know, there may be some new things around various kinds of supplements or NAD and things that are coming out, but there's a whole range of other things that people are exploring, whether it's, you know, massive stem cell injections, 200 million stem cells, IV, they're doing exosomes, ozone, hyperbaric oxygen, they're even doing blood exchange. I mean, there's studies in animals where you can basically hook up a young rat to an old rat and the old rat becomes a young rat. So, there's all kinds of crazy stuff going on. What did you find within Life Force that was the most promising among all those different types of treatments? What should people think about?

Yeah, I'll share a few. And, these are the ones that I know personally because I'm involved. So, one of the companies that Bob Hariri, who's also a co-author and I started, Bob as the chairman and CEO, and I serve as co-founder and vice chairman called Cellularity. We built the largest cellular manufacturing facility out there. It's based out of New Jersey. The company, if anybody is pregnant listening to this, you know that you can store your cord blood, but what cellularity does also is store the child's placenta. We receive the placenta in the facility, we take the cord blood, but then we decellularize the placenta and pull out of it the placental T-cells, natural killer cells, and stem cells. And that's a, you know, incredible treasure chest of valuable cellular medicines and capability. So, you know, I think of this, the placenta as the 3D printer that manufactures the baby. Every cell that becomes the baby has come from the placenta. And, and the placenta, you know, we, we actually pay to throw it away afterwards, but. I want you to imagine that when we mine the placenta for these cells, we have a Bob Hurley says, listen, if your baby came with an extra spare set of organs, would you throw them away? Right. And that's what I think about this. So we're a cellularity is producing large supplies of very high quality stem cells and then exosomes. Again, the placenta is also very rich in exosomes. In exosomes are these small vesicles of growth factors that are pumped out by the stem cells. But then the other cells, natural killer cells, for example, and this is what the company's current business that we went public on back in summer of 21. It turns out that the placenta is an incredibly protective organ for a fetus. If the mother has a viral infection, the placenta and the natural killer cells in the placenta protect the baby. If the mother has cancer, it's very, very rare that you ever get a metastasis to the fetus. It turns out that natural killer cells are the cells that protect you today as you're sitting there against cancer and viral infection. So what we've been able to do is take these most powerful natural killer cells from the placenta and then develop them and use them as drugs and infuse them into the body to augment your immunity. And we have incredible science data, some of which we release, some of which will be released. And so then same thing for T cells and CAR T cells, which you're familiar with. But then the ability to use stem cells. So one of the hallmarks of aging is that the stem cells in your body and these cells are resonant throughout your body, in your fat, in your muscle, other tissues, and these cells that are sitting there latent, ready to differentiate into muscle, liver, lung, kidney, whatever it might be, but your stem cell populations in your body can go down by a hundred or a thousand fold. So, it's this. this ability to repair your body. You know, the analogy that I love, I don't know if it was Aubrey de Grey who first came up with this, he said, imagine you build a brand new mansion. And this mansion is amazing. It's beautiful. It's got, you know, 30 rooms in it, and it's so much work to keep up. But you have a, you have a army of maintenance and repair people in the, in the mansion. But as the mansion goes on, these repair people start to die and they start to go senile, and eventually the mansion goes into disrepair. And this is like the human body where the stem cells are the regenerative agents. They're the repair agents that start to reduce in number 100-fold, 1,000-fold, and as they age, they become less capable. But what if you could augment the stem cells in your body from this really incredibly, you know, this will date us in terms of our computer background, like the boot disk, you know, the earliest software. Yeah. So that's fun. That's a super cool tech.

So basically the idea is preserve your placenta when you're born and then keep it as a storage house for all these amazing healing cells that you can access it anytime when you get sick when you're older. Is that the idea?

Well, yes. And, It turns out that the placenta, it becomes a universal donor. Placental cells are universal donor because they haven't been thymonized yet. If you imagine a surrogate mother who's not related to the child in any way.

Yeah, right.

But she doesn't reject the child and the child reject her. And so the placenta's cells are, are a universal donor and recipient. So, yeah.

People are using like exosomes from placenta and those things, right?

Yeah, 100%. And, and cellularity is developing those products and going into IND, investigational new drugs, idea of, of cells as drugs. Very powerful. Another company, vaccinity, which I'm very proud of, again, serving as co-founder and vice chairman. It's a company that realized, so there's $160 billion biologics market out there. And it's the idea of using antibodies that you inject into your body and those antibodies can go find a specific protein and knock it out. So I have high cholesterol. It's familial, it's genetic, high LDL, low-density lipoprotein, and I don't like taking statins. It's my personal opinion. But it turns out that there's this monoclonal antibody called Repatha against an enzyme in my liver called PCSK9. And PCSK9 in the liver is the enzyme that generates the LDL. I think it's Regeneron makes this monoclonal antibody. They make it in a giant vat in New York and every two weeks I get this little self-injector, five mLs injected in my belly fat and it's about $6700 per injection. It's not cheap.

It's a lot.

And for that reason, it's the last line of defense. But those antibodies I'm injecting into my body go to my liver and they shut down the PCSK9 enzyme and my LDL level falls beautifully in line and it's kept me, you know, really feeling healthy and safe. But it's expensive to have those antibodies created outside the body and so forth. But so what vaccinity, it's V-A-X-X-I-N-I-T-Y is the name of it. What we've done at Vaccinity is been able to design a vaccine that you inject once a year, maybe twice a year, and that vaccine turns your immune system into the producer of those monoclonal antibodies. And so you vaccinate yourself against this endogenous protein, this protein in your body against PCSK9. And so we're in phase one there and phase one on same typical target for migraines, a phase two for Parkinson's and a phase three for Alzheimer's. So it's the idea of imagine being able to give yourself an injection once a year and protect yourself from ever coming down with Alzheimer's.

That would be amazing. You wanna know my secret for living a long and happy and healthy life? well, all I have to do is check out my weekly newsletter, Mark's Picks, where I share my favorite tips for health, longevity, wellbeing, and lots more. Check it out and the link below. So there's gonna be kind of cool little hacks that we can use to somehow stave off some of the age-related diseases. But what you're doing a lot with this work on life force and longevity.

Is actually going upstream to get to the root causes years before you'll ever get the problem. Yes. So I'm one of the, remember we talked earlier about the sirtuins? that are doing this dance between DNA repair and DNA regulation, and they're powered by NAD that's dropping in the cells as we age. And so, one of the things you can do is supplement the precursors of NAD. And this is a lot of the work that's done by David Sinclair as well. And so, I take NMN nicotinamide mononucleotide, that is converted to NAD intracellularly. And that helps to, at least in theory, I've not been measuring my NAD levels, but upright increase the amount of NAD in my cells to keep those sirtuins bouncing back and forth and keeping my epigenome properly regulated. So there are things like that. I take metformin, to reduce my blood glucose levels. And, you know, there's a whole slew of things. There's a number of trials going on, and I'm tracking all of these, you know, age reversal therapeutics and companies out there.

You know, it's interesting when you look at the metformin, for example, I remember the diabetes prevention trial, and it showed that, you know, giving metformin helped to reduce the progression to type 2 diabetes. from pre-diabetics by a relatively good amount. But, the lifestyle and diet were far exceeded the benefit of Metformin. So, is it incremental only in terms of its benefit or, I mean, you think it has some other benefit? Because to me it seems like if we just reverse insulin resistance doing the things that we know work, which is diet lifestyle, that actually you won't need Metformin.

Yeah. So, for me, it's built-in suspenders. I'm really focused in on my diet and my sleep and my exercise. and my mindset and, you know, I'm doing everything I can to maximize my opportunities to intercept the technologies that are coming our way. And it's, you know, it's a choice. I mean, chunky monkey and sitting on the couch watching Netflix for five hours a day is a choice.

Yes, for sure. Yeah, no, that's right. I think, you know, it's interesting to try to sort through all these different technologies, whether it's lifestyle things, supplements like NMN or NAD, and what is the 80/20 on it? What is the 80/20? And I think that, you know, by that I mean, you know, what are the most leverage interventions that we can focus on now given what we know for people listening? Could you help us sort of come down with what are the 80/20 on, on this? What are the 20% of things that are going to make 80% of the difference? and if we focus on those, we're going to be good. And then we can kind of micro tune the other things as the research comes on. We hit this longevity escape velocity.

You know, there is so much data coming out and so this massive increase in information and stories and journal articles and such. I'll just share with you something that I'm pumped about. I built over the last couple of years a platform called Future Loop, and it creates a newsletter for me called Longevity Insider. You go to longevityinsider.org, and it's free. We scan 250,000 to half a million journals, newspapers, magazines, tweets every day. looking for valid future positive semantic breakthroughs on converging technologies impacting health and longevity. So it is a, I get the top 15 articles every day on breakthroughs regarding health and longevity and age reversal. and we have built an AI on it that summarizes the article really well about what it is and why it's important. And for me, it's about how do you keep, part of the mindset part is realizing, holy shit, that's happening and that's happening and that's happening. It's a realization that this area is massively exploding in a very positive sense. so, you know, longevityinsider.org is, you can go and, and, and get on, you know, instead of all of the dystopian news you get all the, every day from everything else you read.

Yeah, absolutely. So, so in terms of these, these things that you're most excited about, is it, is it these Gene editing things? Is it the, is it the stem cell work? Is it this sort exosomes, I mean, what's sort of the thing that's sort of most exciting on the horizon?

You know, I think it's all of these. I mean, we probably, we did 160 interviews in the book, and we look at, you know, I think the gene therapies to be able to, you know, we were all given a genetic lottery when we're born, depending upon our mother and our father, and there are things that you can do and lifestyle changes, which we should and must do, but the tools that are coming to attack the different hallmarks of aging from stem cells and exosomes on one end to gene therapies to, you know, just even treatments for mitochondrial dysfunction. I mean, I'm just, I'm tracking as many of them and all of them. I'm lucky Fountain Life as a platform is where I have a list of an incredible group of advisors and supporters who are the fiduciaries to help us identify and then say, this is scientifically credible. Let's watch this. Let's make this available to our members. And so, I'm constantly tracking that. I mean, there's another technology coming out of total plasma exchange, right, where you basically changing the oil in your car.

You explain that.

You take out, you know, so in our bodies, we're accumulating products of metabolism all the time, and our liver and our kidneys should clear that. But, It doesn't always. And so there is a couple of things happen. One, as you said, experiments done in what are called the parabiosis experiments, where the circulatory system of a young mouse and the circulatory system of an old mouse were connected. And the young mouse got old and the old mouse got young.

Yeah.

You know, and like the, this is like, you know, the vampire experiments. and it was like, what up? What's going on here? What's these factors in the blood that-.

The blood, you cleaned him out.

In this blood exchange. And so two things came out of that. One is out of Harvard, out of Amy Wager's lab came identification of a protein called GDF-11. And GDF-11 is a protein that goes, you produce less and less of it as you age, and there are antibodies against it as you age. And so, in mice, when you give GDF-11, and we're just in the animal phase studies, the mouse reduces inflammation, it increases its circulatory capabilities. You get a lot of revitalization from GDF-11. So, It may be that GDF-11 is the factor responsible for the rejuvenation of these older mice. So that's one thing. And so we write about GDF-11 in the book. I'm an investor in a company called Elevian that is producing GDF-11 or doing the research behind GDF-11. But then these same scientists took these older mice and basically took blood out, spun out the cells, and put the cells back in, but with albumin and dextrose and saline. Basically, albumin, as you well know, is the major protein in the bloodstream. And, your blood is a lot of albumin, a lot of salt water and sugar. And so, they took all of the plasma out and replaced the plasma with fresh constituent parts. And that revitalized the oil and ice, too. And so there is, in particular, reducing signs of dementia. And if you, so there's, there's a lot of protocols going on right now. We're tracking that inside of fountain life. It'll probably become available in our Edge program. I look forward to trying it. And it's a notion of basically, like, changing your oil.

So, so what is it? Plasma pheresis. Is that what it is?

It is basically, yes, it's basically, again, you're, you're pulling out two liters of blood, you're spinning it down, and you're replacing the, the plasma with, with albumin and, and, and dextrose and, you know, it's ringer solution.

So the series is a lot of old crud, like. kind of like space junk floating around in your blood that needs to be cleaned out that can cause aging and inflammation and oxidative stress and all these problems. And, that kind of exchanging your plasma or blood like this will actually help to improve your overall health. And, I think a lot of doctors are plasma freezers and other things for chronic illness and seeing really significant benefits.

Yeah. And, so there's just so many different and, I mean, we we could spend another three hours and maybe we'll do another session to actually dive down into another dozen targets. But it's extraordinary. I've never been more excited about disrupting the healthcare industry and extending the healthy lifespan. And there's nothing more important than that. I love the saying, the man or woman who has their health has a thousand dreams. and the man or woman who does not has but one. I think you're right, Peter.

You're in this moment where the kinds of things you're talking about are not just disrupting aging and longevity science, but they're disrupting our whole way of thinking about chronic illness and subsequently our healthcare system. Now, we need to refocus on the science of creating health because what you're talking about, a lot of the therapies you're talking about are not necessarily targeted at a specific disease. They're targeted at mechanisms that that are related to the degradation of our biology over time that are really about optimizing the inherent functions of the body. So, they're supportive and enhancing therapies. I think of the difference between antibiotics and probiotics. Antibiotics are going to kill a bug, but a probiotic will help your gut work better. And, a lot of these therapies are much like that. They're not designed to be interfering or blocking a pathway as much as actually enhancing and optimizing the functions of your biology that degrade over time as we age. as we have insults, I think a lot of the insults that we see are, you know, because of how we treat our bodies. You know, I got a body work the other day and you know, below the neck, like she said, look how your body's 30 years old. I'm like, yeah, it feels like 30 years old. I mean, I feel I'm actually more fit, more muscular, more in shape than I was when I was 30. At 62 almost. So that's possible if we understand the science of how to create health and how the body works. If you love that last video, you're going to Love the next one. Check it out here.

And the way we teach it is treat the symptom, not treat the cause.

Yeah.

Yeah.

And it's in aging, it seems like there's things that happen and I want to get into why, but we see increase in inflammation and aging. We see a decrease.