← Tom Bilyeu's Impact Theory
Tom Bilyeu's Impact Theory
Civilization Is About To Change Forever: Truth About Immortality, Rich Vs Poor, AI & Ending Disease | Dr. Khan PT 1
01:09:42
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- [00:01]
Dr. Mahmoud Khan
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Podcast Host
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Podcast Introduction Narrator
that humans are born to die and that even if we could extend human life, we shouldn't. I hate that idea and believe that thanks to AI we are on the brink of a biotech revolution that will radically extend human life. To help us explore this frontier, I bring you today's guest, a scientist and entrepreneur who believes that at a minimum, AI is going to dramatically alter health span and that will have thrilling consequences as long as we don't mess it up. In mind, I bring you Dr. Mahmoud Khan.
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Podcast Host
Given the fact that most men lead lives of quiet desperation, why should anybody care about extending their life?
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Dr. Mahmoud Khan
Well, let's think about it from a society point of view and an individual point of view. From a society perspective, if we can keep the majority of people functional and health, I'm going to distinguish between what we think about as healthy versus independently functional, active contributors to society and their family and their loved ones. If we can do that, society should care. The GDP impact as calculated by Andrew Scott, professor at London Business School and Oxford University in England, and others who have verified this data have shown that the impact in the US in terms of GDP is around 1 to 4 trillion dollars of GDP impact just for a 12 month extension of healthy life, not maximal life, but just keeping us healthy. So society absolutely should care. Medicare, uk, nhs, any of these organizations cannot currently afford the healthcare costs of just providing healthcare to people as they age. It's not possible today. We haven't figured out the solution. Well, the alternative is just keep people healthy. They have not only less need for chronic care, but they continue to contribute. Now, at an individual level, most people I talk to and there's been lots of surveys done, people want to remain independent, active and health not defined by a 20 year old. If you ask somebody 20, what is healthy and you ask somebody who's 40 or 60 what they mean by healthy, most 60 year olds will say hey, can I continue to be active? Can I have the mental capacity, physical capacity to be independent and can I contribute professionally or personally in a meaningful way? That's one aspect of what is being, quote, a healthy lifestyle, right? Most people care, that's what they Want. People don't want to live longer if you ask them the question, do you want to live as long as possible? And in their mind that's 30 years spent in a nursing home. Nobody that I know wants that. Very important distinction.
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Podcast Host
No doubt. Now I look at the moment that we're in right now as an incredibly disruptive moment there. Certainly as somebody that lives in the US you can feel the tension ratcheting up, you can feel the sense of divide and when you look at what things exacerbate, that anything that is going to negatively impact the economy is just going to put you in a really precarious position. When we look at what's going on in terms of government spending and the pyramid that's about to flip upside down, where we go from most people are young to most people are old and there are fewer young people that take care of them. When I look at the problem currently of an aging population where health span is not taken into consideration and it's just lifespan and now we're spending just gobs of money on supporting people. From a healthcare perspective, are we doomed if we don't rectify this situation and get those health care costs under control?
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Dr. Mahmoud Khan
Well, I wouldn't use the word doomed. However, I would ask ourselves what are the options we have? Those are challenging. If we do, you know, no action is a decision and if we don't take any action in business as usual, we've seen what's happened the last 20, 30 years exactly as your point. There are economic challenges now, there's labor shortages on top of that, and developed countries where the birth rate has dramatically fallen, the life expectancy over the last 60, 70 years has been extended by at least 30 years. Let's say 20 years of that is requiring significant resources from a healthcare system. Given that burden, societies are asking ourselves what can we do? And you know, it is itself divisive because if you're a young person in a pay forward society and developed countries are a pay forward society, by the way, so are developing countries. Just it's not structured. And so in a pay forward society, I'm a young person working today. I'm supposed to be paying taxes so I can take care of the last generation. Well, if there's a few of those, as you point out in that pyramid, that's okay, that's part of being. But so all of a sudden if you're in China and you're one grandchild with four grandparents, how am I supposed to contribute to that economic model, let alone personally having to take Care. That's divisive, right? How am I supposed to do that? So what are the alternatives? It's going to have to be innovation. Innovation across the spectrum, which means everything from policies of how we think about our taking care of society down to technological breakthroughs. And I don't mean just biology. The whole spectrum of technology to allow leverage of the fewer and fewer young people we have, as well as the ability to use fewer people to generate more and more activity, both financially, but also services. Right? That's true leverage. And industrialization over the last hundred years has allowed humans to create huge leverage in every aspect of our lives. What we have to ask ourselves now is what is that next s curve of that leverage? Right. How can technology help us? What are the policies that will enable that? What's the financial policies that will do that? What are societal norms? How do we enable all of this? And there's multiple aspects of this, not just biology, and which means something that you do for a living. We need to start talking to people in the terms that they understand. And one of the biggest gaps, and I've been in science 40 years, is scientists can't be on their own telling this story. Scientists are not good at telling this story. And what we learned in Covid is what was being said as an expert was not what was being heard. In some cases, it divided us. So I would say part of the challenge is that we have to overcome is we gotta figure out how to get people on the same page to understand what the challenge is. But importantly, also based on clear evidence, point out the opportunity. And the opportunity is huge. Everybody benefits. One other thing about divisive, what we have to think about is the haves and the have nots, not just within a society, but across the world. Every human being is ageic. But imagine a world where you have technological breakthrough which allows a population and individuals to remain healthy longer, more productive, more able to contribute to their society. All great. But if the only civilians and society that can do that are rich countries, then the economic divide between the rich and the poor countries will continue to widen. If that happens, we're going to increase this challenge of haves and have nots. So it's very important that we ask ourselves another question on the assumption that we can have technological progress, and I'm pretty confident that will happen. How do we democratize it? How do we make sure that the masses are impacted in a way that whether you are less well off within the United States, are financially more capable, you have access to this. The only way to do that is democratization of technology. We used to think that some ubiquitous dream, but cell phones told us and showed us that very expensive technology can become ubiquitous. It required not just technological breakthrough, but innovation in business models. And it was innovation in business models that democratized cell phone technology. The poor rickshaw driver in a Asian country has a cell phone. We would not have imagined that possible even 20 years ago.
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Podcast Host
So you talk about the opportunity being massive. What is the opportunity exactly? Just extending the healthy life expectancy.
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Dr. Mahmoud Khan
So let's take a look at. We define retirement age. Let's say 60 or 65. You know, this was defined as I'm sure you know, after around World War II by European countries. And the number was picked because most people didn't live past 60. So it was a great model. Right. Well, I'm going to guarantee you a government pension if you live past 60. Well, if 90% of the population didn't do that, I didn't have to take on responsibility. So guess what? 70 years later, our definition of retirement age in most countries is still 60 or 65. We're assuming that after that age, you're no longer contributing in a meaningful way and you become a net recipient. Well, the first thing that that raises is as soon as you turn 65. Are you now no longer contributing? I would say people are. Churches, charities. If you look at informal contribution to the GDP in the United States, in Europe and the UK and many Asian countries, older people continue to serve next generations in countries with more formal employment. Why should there be in particular when knowledge workers are actually in high demand? Because there's fewer of them. So these are the sort of links that we have to think about and say, what is it we're extending? Right? We're extending health throughout your life, allowing you to contribute through all stages of your life. Then it comes down to choices. I'm not saying everybody should be working till they're 80 because they don't have a choice. But we can choose to contribute. And everybody has a chance to contribute in different ways, whether it's taking care of your grandparents, sorry, grandchildren, providing support to your local church, your local charity, volunteering at the local hospital, or continuing to work as an executive. New careers. You and I have had more than one career. Why should it be one career or two careers or three careers? Why can't it be four careers Now? Is society set up for that? Are we as employers set up for that? I'm going to be provocative. What's the mission of an educational institute if it only serves you? And your Life until you're 22. Is that the only mission of an educational institute? Maybe we have to ask us university presidents that their role in a society is far more than taking teenagers and giving them college degrees.
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Podcast Host
Give me an example. What would you want them to do?
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Dr. Mahmoud Khan
Why couldn't an engineer who was trained in the 70s and 80s be now retrained as a data scientist and an AI?
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Podcast Host
Because they won't want to be hearing. So this is my big concern and I'm going to pull a dark cloud over us for a second. By nature, I am optimistic, but reality is constantly trying to convince me that I should be way more pessimistic. And you said societal norms and I think that may be the thing that we most have to think about. And when, when I think about, okay, people been raised thinking that they're going to get to retire at 65, that they can then put their hand out. They have an expectation that somebody's going to look after them. That, like you said, works. When you've got a ton of people under you and most people have died by then, you're one of the lucky few that's alive. It does not work when you're super top heavy. And that is a position that we're running towards. And I feel like everybody has this sort of generic sense of either AI is going to save us, robo are going to save us magically, we'll, I mean, coming from a us perspective, we'll be able to print our way out of it and just give, print money and be able to give money away and everything's going to be great. And the reality is, I think that people are going to have to fundamentally shift their perspective. But historically, especially when debt gets involved, the only time that people shift their perspective is when there is literal bloodshed. And so I find that deeply distressing. And so when I think about how do we, how do we migrate people to the real opportunity where. So I am very hopeful that not only can we extend healthspan, but we can extend lifespan. I don't want to, I don't want to believe that we're stuck at 120. I know we don't have evidence yet, so I won't, I won't back you into the corner of telling me that it is possible. But all of that is such a radical transformation that even if we just isolate it to the pyramid is going to flip. We are demographics, they're set. There's no way to suddenly have a lot more young people. You can have a lot more infants, but you can't have a lot more 20 year olds. It takes 20 years to get there. So we, the pyramid is going to flip. And now the question is, how do we flip that pyramid? Well, and I think if we don't change societal norms and expect people to work longer and contribute more meaningfully to basically their own caretaking, their own health care, contributing to gdp, all of that, if, if we don't figure out a way to psychologically get people on board with that, we are going to have a real a, a catastrophe that I have not mapped out yet to figure out exactly what that catastrophe looks like. Because you have very angry old people. In fact, now that I say this out loud, the problem you will run into is they will continue to wield political force. And now you will get. You were referring earlier to what's known as the Gini coefficient for people that have never heard that word before, where you get a massive divide between rich and poor. I'm going to guess, though I've not heard of it, that there's an equal psychological principle that is political power. And if you have the old generation wielding all the political power, you will get an uprising of young people who just won't tolerate it. Help me see a way out of this.
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Dr. Mahmoud Khan
So most of what you said were in full alignment and agreement. It's interesting because everything you just described is not to solve a technical problem or a scientific problem, but actually a societal norm and therefore leading to, if possible, policy reform. But you won't get policy reform until you get the political clout to want to do it. To re. Emphasize what one of the things you said in terms of the challenges, one of the things that I read, and I'm sure you saw this during COVID people were starting to actually write in publications. And I remember a letter published in the London Times starting, actually stating, why don't we let old people die from COVID instead of shutting up society. That was in the London Times. So the fact that it got published is not their opinion. Right. In a free press, but it tells you if somebody's willing to write a letter in a highly visible publication. How many people were thinking that? So that's starting to be seen. If that letter is some evidence for that people were questioning in more than one country, quote, we're being shut down just to keep old people alive.
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Podcast Host
Right.
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Dr. Mahmoud Khan
That was Covid. What is it? 80% of deaths occurred in old people. And so we've already witnessed that. Now the question is, what are the learnings? I am a little bit More optimistic simply because when we look at rapid technological change and embracing technology in the past Industrial Revolution, everybody was scared. All these manual workers are not going to have any jobs. Guess what happened? GDPs grew, new professions got created. Then we saw that when we started to see agriculture start to get industrialized, agriculture was the primary employer. And guess what? In the United States, Europe, it's a minority employer now. So we've seen this when we first started to see computers come, word processing, printing, the Internet. Yeah, Lots of jobs got displaced. The newspaper industry is a relatively minor media industry today. Go back to the days of the heyday of newspapers. Very different media has become what you do. Very powerful, reaches far more people. So we've seen this. And once people start to experience the positives, they start to embrace. The question really is, how much of it was forced and how much of it was it people saw the opportunity? Yeah. If you'd asked travel agents 20 some years ago, what do you think of the Internet? You'd have got a different answer than the traveler. So I always think, how do I get the consumer to actually understand the opportunity and embrace it and then bring them along? That needs to be set. Then science provides a solution, not the other way around. If we lead with the scientific argument, we're going to end up in a very scary place because it's misunderstood. So I'm a little bit more optimistic because I've seen there were times. Let me give you an example. There was a time, if you go back post World War II, people used to hide a diagnosis of cancer. It was a taboo. So if you got diagnosed with cancer, you didn't tell anybody why? Because cancer was a lethal diagnosis. If you got told cancer, it's done, it's over. It took a pioneering woman who took on the cause of breast cancer and said, I am going to create public awareness that cancer can be conquered and the world doesn't have to be this hiding taboo. Guess what? The National Institute of Health was created as the National Cancer Institute. It took a whole movement and over the next 40 years we found the mechanisms of cancer. And in many cases today, cancer is treatable and curable.
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Podcast Host
So what's the analogy? That getting old is not the terrible thing that we once thought it was, that you can be thriving and a strong contributor as we get older.
- [19:43]
Dr. Mahmoud Khan
Most people's mindsets, the consumer, you ask, tell me what it means to get old. And the first thing they think about is the visible part of people that might think it's onset of dementia, pain, immobility, rigidness. They won't use those words. But all the negatives that are associated with the decline in function of our bodies and minds as we get older, that's the image. So if you ask people, you know that is the inevitable outcome. That's what they see. And yet it is clearly evident that loss of function at the pace that we've seen is not ubiquitous and certainly not to be assumed is going to happen to everybody. In fact, in the majority of cases, it is likely something that can be slowed down, if not halted. Now, how do you bridge that current understanding with the technical reality of what's possible? And one of the reasons I avoid saying we're going to live longer, although I'm not actually questioning whether we can live past 120 or not, I'm a pragmatic person. Let's show that we can keep people healthy as long as possible first. And if one of the benefits of that is that people live longer, so be it. But the primary goal right now in my mind as a personal opinion, is keeping functionality and healthiness for as long as possible for as many people as possible. I always add that this is not for the benefit of a few wealthy people. This should be for everybody. We don't do that. We're going to have a true societal challenge.
- [21:26]
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- [22:26]
Podcast Host
Yeah, it's a very nice way of saying that we will have revolt on our hands. It's. It does become a dystopian nightmare very fast if people, one class of people are able to buy their way to immortality and feeling good and all of that, and the other cannot. But it's going to start there. As you look at this landscape, as you lead people through this landscape, I think that that's going to be one of the big challenges that you face. How do you think about that right now in terms of one, what breakthroughs are real, what's happening right now? And then how are we going to make sure that that is cheap enough that everybody will have access to it?
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Dr. Mahmoud Khan
So first of all, let's look at the fact that there are real differences which seem to be not just simply purely driven by biology. So if you look at the differences in what life expectancy is a start. If you look at the United Kingdom, if you live in Glasgow versus if you live in London, your life expectancy is at least 10 years shorter in Glasgow.
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Podcast Host
Now, are you saying that's class based?
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Dr. Mahmoud Khan
It's certainly zip code code based. We know that socioeconomic situation which is correlated with your postal code or zip code is an important driver of that. How much of that is choices versus lifestyle versus the environment you live in? All those are complex. Now, without getting into the biology of all of those interactions, clear that our human life expectancy and maintenance of health is driven by some factors that appear outside our own control. It's a function of where you were born and grow up. On the assumption that if you're in Glasgow versus London or some parts of Chicago versus another part of Chicago, wherever you look, there are clear disparities. Those disparities are helping us understand what are the mechanisms driving that we can keep populations healthy by understanding those differences. That's one public health population level evidence. Another we've seen is populations living in certain parts of the world. The so called blue zones clearly have longer life expectancies. What is the difference there? What is it about growing up in some part of Italy or some part of Greece, or some part of the northwestern part of Pakistan and India, parts of Japan? All over the world there are these blue zones. What is different about those populations? And it's easy to say, well, it's their lifestyle choices, but there's clearly learnings in that. So that's the human evidence. Now we look at animals, we have observational evidence that different species live longer. But more importantly, starting with very simple single cell organisms, which was first shown decades ago, all the way through now to primates, monkeys, we've shown that interventions including therapeutic potential drugs, not approved drugs, potential drugs, in some cases drugs that could be repurposed, can change the life expectancy of otherwise randomized matched animal groups. So that's reason to believe that this is possible. Now, is it safe? What's the optimal way of doing this with humans? Those remain to be determined. The last piece, and I'll give you an example of this. It raises the question, if biological loss of function has happened, can that decline be slowed or reversed? Well, if you think about the evidence from things like epigenetic reprogramming, without getting into too much of the technical jargon, essentially our DNA sequence, our genetic code is the same today at my age, in my 60s, than the day I was born. My genetic code hasn't changed. The ability of my cells to read that code and replace themselves clearly has changed. So the question really is, is there something wrong with my genetic code or is there something that is. I'm losing the capability of translating that genetic code. There's more of it there than the genetic code because my DNA is the same. And it's already been shown by people like Yamanaka, who got the Nobel Prize for it, that you take adult cells and you can actually change them back to genetically pluripotential youthful cells. So the code was always there. Now there are animal models that it's been shown in already in rodents, mice, and now even in apes and monkeys, that you can take a diseased tissue in a living animal, reprogram itself, such as in the retina, and restore function. The most powerful evidence was on the COVID page of Nature from David Sinclair's lab at Harvard, where he took animals that lost vision from glaucoma and age related eye disease and restored their vision by epigenetically reprogramming their retinal cells. That's powerful. It tells you what we used to think was permanent loss of vision, actually to a degree. Now, how much of it was restored, we can't measure in an animal, but we can show that it was an animal who couldn't see light, now can see. That gives us a lot of optimism technically to figure out what's the next step to go from. We went from worms, yeast, to mice to monkeys. Next step is how do we take that to humans in a safe manner? We're that close.
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Podcast Host
What are the breakthroughs that you're most excited about in longevity?
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Dr. Mahmoud Khan
You know, it's a common question. I get that. Since we're an investment team as well as a science funding team. If I knew the answer to that, it'd be a trillion dollar answer. I think there are several both pathways and lines of evidence that excite my team, myself, my peers in other organizations. We're actually approaching this, say where is the highest chance of success in keeping a portfolio. But I've been in science for 40 years and one thing I learned is you have to maintain the portfolio. I'm of a school of thought that I don't think it'll be a single breakthrough. Some people think, you know, we're going to find the pathway that results in age related decline and we're going to be able to treat it. I think it's going to be different pathways to different levels of emphasis and importance in different humans. And what we're going to figure out is what they are and what combinations of those are most active in you versus most active in me. And if I can personalize it to that level, then I'm likely to address this. And I think the simplistic view of I'm going to find the elixir of youth as one molecule that we're going to put in the water supply and suddenly everybody's is so naive. And it underestimates the complexity of biology and the ability of biology to adapt. We've had a billion years of evolution of life. It has created all sorts of intricacies. We have to recognize that aging is common to just about every living species originating from that one common cell a billion years ago. And if it's that primeval, then it's probably got multiple bifurcations over the billion years of life's evolution. We need to understand this is where AI and the modern technologies, where computational capability and biology are coming together are going to unlock some of that. It will be more nuanced and personalized than that. Maybe in your case, your eyes are aging faster than your heart. In my case, my heart might be aging faster than my liver in another person. We all know people whose body has aged, but their mind is sharp. We know other people whose brain has aged, but their body is young. And so we know just from observation, aging is not a single uniform effect. It's a common term for probably a lot of very diverse processes which manifest in people in very diverse ways. Yeah. I hope that gives you some context.
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Podcast Host
It does. I'm going to paint a picture of the future and I want you to tell me where I go wrong. So when I think about extending human life, whether we're. I'm talking primarily about the combo of healthspan and lifespan. So this is only exciting for me anyway, if we make 120, just. You can count on that. And the way that you can more or less count on getting to 65, I want to be able to count on getting to 120 and feeling like a million bucks. Okay, so if I were in your shoes and I had to start making some bets, the thing I'm going to be going from first principles and the thing I would want to bet on is what are going to be the things that can identify the patterns. So my base assumption that everything rides on top of is that the human body is one. To your point, it's individualistic. So you have to be looking at the level of the individual, but there are going to be large patterns that you can pull out of the data. So while every human is going to be different, I will learn a lot more from population level data sets on humans than I will from mice. Right. So AI is going to be able to parse through all that. And instead of us taking these rough swags at blue zones and what is it that they have in common, it's really going to look at. Okay, I'm going to take, let's say humans fall into 42 categories. I'm going to break the humans into 42 categories. These are the chunks that they break into. These are the people that age. Brain first, these are the people that age. Heart first, whatever. These are vascular diseases. Peter A.A. breaks these down into the Four Horsemen of Death. He says heart disease, cancer, neurod, degenerative disease and type 2 diabetes. All right, type 2 diabetes is all lifestyle choices. That, that is a self made problem,
- [32:37]
Dr. Mahmoud Khan
but I disagree on that. But we'll come back.
- [32:39]
Podcast Host
Really? Yes, I'm very eager to hear about that. The other three or four, depending on your take, are almost certainly just predispositions for a weakness to aging. So okay, I'm making bets. Number one is going to be AI it's finding the different patterns. Number two is going to be how are we going to go about grouping those things, whether it's the Four Horsemen or something else. And then how do we actually go about resolving those issues? So so much of this is going to be about vasculature is my gut instinct. And so how do we actually go in and address those? One is going to be lifestyle. So just whether it's a wearable device or whatever that tells me to eat this, go to bed here, there, whatever, and you remove from me the need to think about it and to know it just tells me what to do and I do it. But we're also either going to have to find a way to make people care less about doing the things that we'll call bad behavior. So take Zic. O. Zic is a weight loss drug. Just makes you less Hungry and so you don't have the sort of human compulsion to go eat that thing. So now you're not doing a bad behavior that's going to cause you a problem, or I have to create something that stops the bad behavior from being bad, if that makes sense. So those would be the areas that I would look for. Pattern recognition, investing in AI, probably AI, again in terms of getting down to the individual level and sort of wearable technologies about what you should do when at the individual level. And then the last stop on the train, whether it's going to be drugs or other medical interventions, actually going in at the cellular level and making the changes. So those would be the three buckets that I would be thinking about where I'm looking for the innovations. What's the flaw in that thinking?
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Dr. Mahmoud Khan
So let me add a fourth. So I wouldn't say there's a flaw in the three. I think they're all valid. Come back to the choices.
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Podcast Host
Type 2 diabetes. Yes, we'll come back to that for sure.
- [34:44]
Dr. Mahmoud Khan
There's a fourth. And that is in the broadest. And we can get a little bit more specific in a minute. But in the broadest sense, our only real way we measure age today is based on your birth certificate. I look at the day you were born and I tell you this is how old you are. It has almost no way of understanding, even when I've aged, that these two people are of a different age. And we can all know 60 year olds that look perceptively 80 and we know 60 year olds who look 50 or 40. Right. So there's a clear difference. Some of those may be choices they've made over their lives, but people have aged differently. But we don't know how to measure from one person to another. How do you measure age, let alone how do you measure it at an organ level? And yes, there are technologies that talk about methylation of DNA and this, that and the other. But to measure age in an effective way, you need to be able to measure three things. One, I gotta be able to measure what your age is today. However, if I can measure your biological age today, that doesn't help me other than I'm going to tell you something you probably already know, which I feel older than I am or I feel younger than I am. So it's a diagnostic with little other utility, perhaps helping you intervene more in lifestyles more aggressively with one person or another, I don't know. The second thing that measurement has to be able to do is to be able to predict for me the Gradient and the rate at which you're aging. Now that's a much more powerful measure because if I could measure your rate of aging when you were 30, I might be able to tell you you're on a much steeper slope than somebody else. And therefore you should pay attention to this. I don't have that technology today. And the third characteristic should be able to do is it should be able to reverse if I make the intervention, which means I can demonstrate to you. But because of the intervention, whether it is lifestyle or it's a treatment or a device, this is predicting you're gonna live 10 years longer. That fourth variable does not exist today technologically. Until that happens, we are not gonna be able to design the clinical trials, the therapeutic protocols, the clinical protocols by the clinicians in the field to actually be able to do something about it. I'm gonna give you a diabetes analogy. When I was in med, I'm an endocrinologist, I spent my professional career treating diabetes and researching diabetes. If you think about, if you go Back to the 70s, when I entered medical school, hemoglobin A1C was not available. Finger stick blood sugars were not available to be able to do your own blood sugar. And even those did not become useful until it was shown by the Diabetes Control and complication trial that A1C correlated with outcome of complications. Now, I had something to say to my patients saying this is your A1C. If you bring it down by 1%, your risk of eye complications goes down by X. The equivalent of that doesn't exist in aging. So it is going to be very critical for investment and funding to answer that question. Hasn't happened. The NIH has not seen it as its mandate. UK Medical Research Council has not made it priority to actually invest in developing the science to be looking at the so called biomarkers of aging with the three characteristics that I just showed you. Somebody's got to do that. Now, industry won't do it because you can't patent these things. I don't want them patented. Why? Because if you patent them, you will restrict their general adoption and if you restrict the general adoption, you won't get a standard benchmark by which to compare things. So I just want to make sure there is a fourth pillar that very few people are talking about and yet it's the key enabler to the others. The other three you just said are not going to happen until we get this done. So that's one. So should we be investing there? Absolutely. My organization. We clearly said, listen, you've got to go after this and make sure it's open source. Why? You want the best science to be adopted by industry, by the regulator, recognized, Remember, and I'm sure you know that statins didn't take off until we had LDL cholesterol. It was the fact that we could measure LDL cholesterol as a predictor of vascular risk and something that correlated with reversibility of that risk that you started to see a whole family of drugs. What is going to happen in aging? Got to do that. That's number one. The second is, while these exist, we are free living humans exactly to the point. How do they interact between them? Is it truly a biological intervention versus a sensor and a device? And at what point does a biologic become a device and when does a device become a drug? We are actually at the point with nanotechnology and all these other new technologies where it's questioning even our scientific definition of these separations, let alone our regulatory definition. What if it's a combination of a device and a drug that's delivered in a certain timed way? Should that go for regulatory approval as a device or a drug? I could tell you there's challenges even our regulatory environment, because we don't know where they fit. We're trying to reverse fit things where biology doesn't naturally go there. So it's more nuanced is my point in that. And this is where we're having to now start to say, where can we unravel some of this complexity? And I totally agree with you. Big data, AI and large population sets will help us do that. But at the same time, I'm a firm believer in bringing the policymakers and regulators to the table. This meeting we're at today is very much including that because we need their guidance and their coming along this journey to help us understand. So we deliver to policymakers what they're going to be expecting and help them shape us and vice versa. So that's where things will change.
- [41:09]
Podcast Host
All right, so when I think about blood sugar, a continuous glucose monitor is. Whenever somebody asks me, you know, what should I do to radically change my health? My answer is always, if you let me put a CGM on you and you let me dictate what you eat simply by the readings that I get on your cgm, I will change your life in. In ways that they couldn't possibly imagine. Fat loss being the easiest, but your joints hurting, your sleep patterns, all of it is going to be dramatically impacted by that. Do you. Is there anything in the literature Because I know you're going to hate the sort of vague question. Is there anything in the literature that indicates what aging actually is or are we literally blind at this point to the nature of aging?
- [41:59]
Dr. Mahmoud Khan
I think there's a lot of literature that tells us what the aging process is at a cell level. Very, very strong literature around that. A lot of, to a lesser degree, but still powerful literature that helps us understand the aging process at tissues and organs. In various different organs to different degrees, we're starting, you know, probably the least understand might be the brain, but in other organs we're starting to understand that musculoskeletal bone col. You know, is there
- [42:28]
Podcast Host
anything that the different systems have in common?
- [42:31]
Dr. Mahmoud Khan
There's a few. For example, senescence, the so called accumulation of what the lay literature, sometimes called zombie cells. Cells that are not functional but haven't died and got eliminated. Senescence is a fairly common phenomenon that we're seeing. Telomere elongation is a common phenomenon observation. There's a lot of question marks whether it's something you can intervene on.
- [42:57]
Podcast Host
You know, is it elongation? Isn't it the shortening of the telomeres
- [43:01]
Dr. Mahmoud Khan
that elongation, sorry, is an intervention.
- [43:03]
Podcast Host
Got it.
- [43:04]
Dr. Mahmoud Khan
Right. And so those are common. Which of those are mechanistically a cause and are reversible? Right. Senescence probably has some of the most powerful literature.
- [43:18]
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- [43:48]
Podcast Host
What causes senescence? Is it the breakdown of the methylation of the DNA itself?
- [43:54]
Dr. Mahmoud Khan
Well, so what we know is what senescence cells are not doing is functioning normally. What we know is that they're releasing molecules in their vicinity, so called paracrine effect, local effect of these molecules, changing the function of normal cells, recruiting and attracting inflammatory cells into those tissues. So we know they do all of these things. Why some cells become senescent and why some individuals accumulate more senescent cells than others. That has not been fully understood. On the other hand, we have knowledge that certain molecules, treatments, drugs can reduce the senescent load of tissues. We also know that reduction is associated with improved functionality. So our knowledge has progressed all the way to understanding that mechanism in this pathway, for an example, it is ready and there are clinical trials going on in humans today where drugs that actually reduce the senescence load or reduce the impact of that senescence actually are underway today. So that's an example.
- [45:05]
Podcast Host
What's the mechanism that they're targeting? Are they just trying to kill the senescent cell or are they actually making the senescent cell perform better?
- [45:14]
Dr. Mahmoud Khan
3 lines of interrogation or trials. One is target and eliminate the senescent cell. Just reduce the senescent set load. One of the challenges there is how do you identify very precisely a senescent cell from normal and eliminate them. Another is to reduce and buffer the impact of that senescent cell. Right. Either by reducing its function, et cetera. And the third is change the decline of the normal tissues as a response to that. So there's different pathways that are being approached. Of course, we have to remind ourselves that senescence exists at certain stages in our development for important functions too. Recovering from healings from a wound requires some of those senescent pathways. So completely blocking them and eliminating them to zero may well be quite detrimental. So what is the sweet spot? So we know, coming back to your question, there are powerful mechanisms that we can intervene. We're learning with precision how to do that. Will that happen? I'm pretty. One of the things I would say I'm confident eventually we're going to figure this out. We're at that stage right now. It's a matter of time, resource and investments. Who will figure that out? Exactly. Of course, if we knew that, that's the only company I'd be investing in that we don't know. We think about the MTOR pathway, right? It's a commonly quoted pathway everybody's heard or many people have heard of. Why don't we just give Metformin to everybody and this is going to slow down. Is probably one of the most widely used drugs, as you know, for diabetes. Clinical trials in patients with diabetes has shown that survival is better in metformin treated patients. Nir Berzeli and others have shown in multiple publications that this is a powerful impact. It is proposed that metformin's benefit is working through the MTOR pathway. Can we come at drugs that are more specific? Very encouraging data, including in humans. Have we proven it yet and will everybody benefit from it without risks and side effects? Those trials. Some of the trials are underway. So we are at human trial stage in a number of these pathways.
- [47:35]
Podcast Host
Are you taking metformin, one of the
- [47:38]
Dr. Mahmoud Khan
Things I've learned to do as a physician is never answer what I take.
- [47:42]
Podcast Host
Really? Because you're worried people will copy you or what?
- [47:44]
Dr. Mahmoud Khan
Exactly. So I, you know, as I said to you, I am an endocrinologist. And then one of the commonest questions I get is, well, if you were in my place, would you take it? And I always turn around and say, if I was in your place, I wouldn't be treating myself.
- [47:59]
Podcast Host
Interesting. On a podcast. That's a terrible answer. I will tell you that right now. So here's my take on this. Let me know what you think. I've had a lot of people on the show that do take that. That takes a whole host of things that are getting a lot of praise, and I have not taken any of them because I am so paranoid about isolating compounds. And I have a very bad feeling that so often something that's marked as a wonder cure now, a year from now is, oh, actually, sorry, that was killing you. And I'm super paranoid about that. I. The fantasy thing that I hold out hope for is AI and just the ability to recognize patterns in an unbelievable volume of data. And that right now feels like the missing piece to me is we, we need a way better understanding of all the complex interactions. So, for instance, maybe if you are diabetic, taking metformin is incredibly advantageous. And the. The length of your life would have been shortened were it not for metformin. But if you don't have diabetes, taking metformin now actually shortens your life. It's gonna be complex. Or if you're getting enough sleep every night and you take metformin and are diabetic, then it's advantageous. But if you're not getting enough sleep, blah, blah, blah, that you end up with a lot of complex interactions. And until we can look at the whole data set, how much sunlight are you getting genetically? How well do you produce vitamin D? Like, there are going to be so many complex interactions that unless you're really looking at something that's truly n of 1, you're never going to be able to figure out what the right play is. And so for me, the thing that I'm trying to do is stay alive long enough for us to get to what is often referred to as escape velocity so that you're you. For every year that you live, we now add more than a year to your life expectancy. And so theoretically, you are immortal. I don't think we're ever going to actually achieve immortality, but that's probably a different Conversation. Yeah. So because I'm not a doctor, I don't mind telling people what I do. But that, yeah, I would really tell people to be wary of isolating compounds.
- [50:34]
Dr. Mahmoud Khan
Let me respond and react to one of the things that you said, I think which is very powerful and it raises a dilemma we have in society and in the field. Clearly, if you have diabetes and unless you have a contraindication, metformin in most doctors opinions is the first line of drug. We also know as clinicians that if you are at risk of diabetes and have impaired glucose tolerance, giving you Metformin is likely to delay the progression to full blown hyperglycemia based on a threshold for blood sugar. Now it's a continuum. So it's sort of an artificial biological threshold, but we call that a threshold. Right. There is no drug approved by a regulatory agency for the prevention of diabetes. Even today there are diabetes drugs. Where are diabetes drugs that we know reduce the progression but they're not approved for that. There are lots of reasons for that, but one is to take a drug like Metformin. Do I advocate that everybody who doesn't have diabetes should be taking metformin? No. Some people can have significant reduction in vitamin B12 levels, which has complications which can cause harm. We know your ability to build muscle from resistance exercise. I'm not talking about big bodybuilders, but resistance, which we know is a good thing, is mitigated if you take metformin. So you put on less muscle if you take metformin. So we need to understand not only why, what is the implication of that for the individuals who do take metformin and how do you overcome that? Right. Is it more exercise, a different lifestyle? So there are always trade offs. And to your point, we need to understand, well, there's a way we can do that, can do a randomized control trial of healthy individuals, look at known age related endpoints and do a Metformin trial. Why hasn't that been done? Well, first of all, and this is a personal opinion, it's a drug that's very cheap, 5, 10 cents a pill, if that, no patent, there's no branded version that is going to sell to make money from it. And so industry, for good reasons, no shareholder is going to pay a company CEO to go and put lots of investments into proving the metformin works. On the other hand, government agencies don't typically invest in doing large clinical trials for generic drugs. It's not on their radar screen who's going to do it. And so I think one of the questions we have to ask ourselves in this whole field of what I look at as repurposing drugs is when drugs are either near off patent or have gone off patent, can they be repurposed based on much greater science understanding after they've been on the market to where else they could do that requires a couple of things. One is the funding. The second is drug companies compete on my drug is more effective than yours, it's a good thing. That's the private sector competitiveness. But it raises the question, should we ask the industry to pool all their safety data and so that for the common good, safety becomes essentially open source, so that as drugs are on the market, we start to understand their safety profile? Because the benefit of a drug is two sides of an equation, efficacy and risk. It's both. We talk a lot about efficacy, but we can actually accelerate our understanding of safety by a lot of this changing and sharing data even while a drug's on the market. And then after it's gone off the market, really pooling that. How do we bring that about? The AI on just a population level data set will get you so far. Actually studying large data sets of people who've been treated in structured trials will give you a whole other level of complementary depth in understanding. But you need to have access to more than one trial. Do you see where I'm going? So those data sets, and I'm not talking about the publications where you do some meta analysis based on the data that's published, but actually getting at the source data and really interrogating it will open up all sorts of things. Now that raises litigation questions, risk, all of those, but they're all solvable. The last piece of this data, I don't think we're going to be able to really unlock the power of AI and large data sets until we start to understand how do we do that protecting privacy without blocking access to it. And so that's going to take.
- [55:24]
Podcast Host
Without blocking access to what? The data being collected.
- [55:27]
Dr. Mahmoud Khan
Right now, if I went into a government data set in most developed countries and I said I want to look at the population data set to really understand this, I cannot just simply go in as an academic researcher, I can look at claims data. Medicare for example, gives me access to it, but that tells me reimbursement data, claims data only tells me what was optimized for billing. Can I get into understanding actually what the clinical record showed, not what was billed? And there's lots of literature that shows the claims data I'm using as an example does not fully represent the clinical data set.
- [56:09]
Podcast Host
Do you think people should have to assume it was an anonymized. But should people have to reveal their data? So I'm imagining a future where we're. We're wearing our. It's not a cgm, but you're wearing something that's monitoring your blood levels on let's say a hundred different variables. And we're also tracking mortality. So I can see this person has this blood profile and they live this long, they have these ailments. They complain about this. Again, anonymized. But do you think people should. Ought they. I won't even say legally. Do you think morally they ought to give up their data?
- [56:49]
Dr. Mahmoud Khan
You've raised the powerful point. Right. And a very insightful question which is to what extent do you balance the individual versus the common good? Right. This principle allies not only to medical but lots of things. And there are lots of areas where we do give up our individual rights for the common good. Take a contagious infectious disease. We did this in Covid. Right. If you were COVID positive, we gave up certain choices. And in some countries you actually had a passport. And if it was positive you could not enter certain buildings. That was. We gave that up. Wearing a mask was giving up our individual choice for the common good. So now it really comes back to. To what extent are we going to ask people to do this and to what extent. So do. As a scientist, do I think there's going to be a huge significant public health and population level benefit? Absolutely. But I'm not a social scientist to understand what will it take? Okay. I am very wary simply because we're living in an increasingly divided. Cautious, to use a very mild term. But the world is almost to the point of lost trust.
- [58:08]
Podcast Host
Almost.
- [58:09]
Dr. Mahmoud Khan
Right. Lost trust.
- [58:11]
Podcast Host
I would say we spilled over.
- [58:12]
Dr. Mahmoud Khan
Yeah. And if that's the case, then asking people to go that far, I don't know how it's going to happen in many countries. People are going to have to be convinced of the word. You said anonymized. I think the challenge in my mind is people don't trust that. It's anonymous.
- [58:30]
Podcast Host
Yeah. And I think that they have reason to trust it. It's interesting. I was asking you a question to which I don't know my own answer. So I'm gonna think out loud. I, I am hyper American, so I don't think people should be forced to do it. But I do think that they're. I think it would be very wise of governments to incentivize giving your Data in a way that is anonymized. The government is going to have to earn trust with that because, good Lord, I really don't think they've done a great job of earning people's trust. But that would be, that would be where I would want to lean. I would want to see people incentivized to give that information. I would want to see that information protected as fiercely as something can be protected. And look, I'll anticipate the comments in the feed saying I'm being naive. That is almost certainly true. But nonetheless, I, this to me feels extremely consequential. So I am a big believer that if we can live forever, if we can live forever, we should. It's very interesting. I'm going to make that statement for now and then we can, we can challenge it. But I, I would love. I really want to live forever. I will say that. That, that I can say with confidence. I really want to live forever. I do not see any way to get there without AI and an obscene amount of data. Given my proclivities for personal freedom, I don't see a way to get there other than to incentivize people to give up that data. If I, even though I know my data will be breached, if I'm honest, I would give it up if that meant I could be a beneficiary of that information.
- [60:16]
Dr. Mahmoud Khan
Well, let me give you an example. When you voluntarily give up that data, if you want to buy a life insurance policy today for which you see a perceived benefit for your loved ones. Usually the reason we buy life insurance policy, you give up your medical record, you go to a doctor, you get a physical exam and you disclose your life habits and all the rest of it. That's expected and people do it. Most people who are buying a life insurance expect that that's going to happen. If it's provided by your employer, you get a limited life insurance policy, then you don't. But everything else you buy, we're used to seeing that. And I look at that analogy and I say that's a choice people who buy policies make and they clearly have a value from that. Can we learn from that behavior? That's one to one benefit. But now you're talking about getting a population. But let me give you an interesting dilemma in the aging field. Remember we talked about how to measure your age, your biological age. If I give you a buy a life insurance policy, I use a date of birth. If I get a job, I provide my date of birth and my age is taken into account. In terms of my employability, not from discrimination, but retirement age. And employers look at how many years can we expect this person to work? All the rest of it. Let's say I could tell you that you are 10 years older than your birth certificate. Should you be required to disclose that to your life insurance policy? Should they take that into account? Is that part of the actuarial equation? Should your employer know what your biological age is? It certainly affects your employability, certainly affects the actuarial tables. So we're going to be actually facing these questions in the not too distant future. So what you're raising is absolutely hypothetical. True. I'm just saying it's going to become a practical reality in specific applications that we haven't anticipated yet. But just imagine the day I can tell you that you are aging 20 years faster than your peer. You. Should you disclose that to your family? Should that affect your choices that you're making for your children? Should it affect whether you should have children or not? There are going to be questions that technology is about to unlock, enabled by big data and all the rest of it that we haven't even started thinking about it.
- [63:01]
Podcast Host
Yeah, this is where it gets very interesting. So I will ask the audience to forgive me if I change my mind down the line, because I am definitely thinking about this for the first time. But here's how I would approach that. I would certainly want to know that information. I absolutely would not want my employer if I wasn't my own employer. I would not want them to know that because it becomes far too easy to black hole somebody in that. Nah, I just don't like that data point. And so now it becomes impossible for somebody to get a job. For instance, my dad, as he was nearing retirement age, dyed his hair because he was completely gray. He dyed his hair when he went on a job hunt. And I say, yeah, that's a smart idea because it subconsciously gives the cue of youthfulness and vitality. And I think positioning yourself with the full recognition of how you will be perceived is very wise. And so there is just a truth that I think we want as the individual, we want as much control over people's perception of us as possible, and especially if they hold some sort of consequential sway over you. However, when it comes to life insurance, I'm asking you to take a bet on me. And the more that we can get to an actuarial certainty, I think that's more fair. So from a life insurance perspective, I do think that that is worthy of them or worthy for them to require that. And at my previous company, we took out keyman insurance on me. For people that don't know what that is, it's the assumption that if something happened to you, that would have a material impact on the company. And so the company will sometimes take policies out on a small handful of people. And so I had key man insurance on me and I did not enjoy that process that I felt like a piece of meat. But at the same time I was like, hey, I'm asking millions of dollars if I were to die. And so I was like, yeah, okay, I get it. To your point, these are things that we are going to have to suss out. And I think that people are going to need to start forming opinions about this stuff. People are gonna have to going back to that idea of societal norms, we are going to have to start making decisions about what this stuff means and getting this propagated out there as quickly as possible. So now let's really get gross for a second.
- [65:33]
Dr. Mahmoud Khan
Okay.
- [65:34]
Podcast Host
This might go back to what you were saying about you took exception to Peter attia ranking type 2 diabetes. Or maybe it was the way I positioned it. So I'm not speaking for Peter Attia. I will speak for.
- [65:46]
Dr. Mahmoud Khan
Peter's a friend, colleague, amazing human being.
- [65:49]
Podcast Host
I love that guy more than you know. But the reality is type 2 diabetes, according to Tom Bilyeu, is a lifestyle choice. People are choosing to have type 2 diabetes and if they let me control what they eat, they won't have type 2 diabetes. And so I do think that there are certain things that are within people's control. And if you are doing a self inflicted wound like smoking, that I will say, yeah, you are going to get put in into a bad category of life insurance of a whole host of things. Your health insurance should be more expensive if you smoke. But by my standards, it should also be more expensive if you can't modulate your blood sugar appropriately. What say you?
- [66:42]
Dr. Mahmoud Khan
So I grew up and got trained in endocrinology and specifically actually diabetes and metabolic disease from the school of thought that advocated exactly what you said. That's how I was trained, that's how I practiced and that's how I taught. I was an academic center, actually all my practicing career. So if I reflect back and if some of my students and former students are listening, they'll say, well, that's, that's Dr. Khan, that's exactly what you were advocating. What's caused me to question that? Do I have evidence to counter what you've just said? Indirect. You mentioned the GLP1 agonist. Right. GLP1 agonists on the surface cut your appetite and therefore you make better choices. As a neurophysiologist biologist, which I'm not a neurophysiologist but if you ask the neurophysiologist, they raised a much broader question. It actually does more than that. It changes the whole gut incretin communication, the biology changes. That's one line of evidence that suggests this is more than just cutting the appetite, it's changing our metabolism. And so it becomes this chicken in the egg question. Is the diabetes prone person making bad choices, making them diabetic or is it their underlying biology that becomes this vicious cycle? I think this last round of therapeutic interventions has really raised questions in the minds of endocrinologists.
- [68:24]
Podcast Host
Let me ask what's going to question because you might know something I don't, but I doubt it. If you let me control what somebody eats, can we agree that if you give me a hundred diabetic patients and, and remember I control what they eat, they're locked in a room, they can't touch food that I don't give them, that I can get 100% of them to no longer be a diabetic, I
- [68:51]
Dr. Mahmoud Khan
can say, look, there's no question, when I used to teach this philosophy, I used to say if you go to a refugee camp or you go to any mass gathering crisis after a war or wherever people are now hungry, you'll over time find no patients with type 2 diabetes. Just about that tells you is if you force human behavior to an extreme environment, lock them up in a room, of course they're very biology will reset. That doesn't mean to say that their underlying biology is normalized because the minute they're out of that environment, they rebound. Okay, that's one. The second is I'm just going to add another variable which I find fascinating outside my area of expertise. Fascinating is the whole understanding or greater understanding of our microbiome. We know if you take certainly animal experiments, and this is maturing rapidly, you can take an overweight animal, transplant those bacteria into an underweight animal and the underweight animal metabolism has changed and vice versa. In fact, force feeding experiments are even more exciting because you take a thin animal's microbiome, put them in another animal and try to force feed, it still won't gain weight. And so is that choice because there you're force feeding it, which is sort of the hey, I'm eating even though I don't need to. And if you put these different pieces of evidence together, it starts to raise a question where is the distinction between choice and biology of the underlying itself? I don't think it's that black and white anymore. And I've been really real self reflecting and asking myself were all the assumptions and the norms that I accept adapted actually now being challenged? It's no different than the discussion we've had around aging. What is inevitable versus what is the underlying biology and the environment. Now the microbiome I find even more fascinating and simply because it then raises questions around even the environment we live in. Okay, we have as modern humans, changed our environment in dramatic ways. Many have had powerful public health impact. But was there a price? What's the consequence? And how do you mitigate and what are we learning from that? So I just, I hope we have nothing else to achieve from this. To raise a seedling of a doubt to maybe we don't have the answer that black and white when you manage
- [71:43]
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