96. Dr. Eric Verdin: Why Most Longevity Claims Are Wrong and What Science Actually Shows About Aging

What if everything you've been told about longevity supplements is based on hype rather than science? Dr. Eric Verdin, CEO of the Buck Institute for Research on Aging, joins me on the Extend podcast to separate fact from fiction in the longevity field. We explore epigenetic reprogramming, why the immune system controls aging, and the reality that no supplements are proven to extend human lifespan. We also discuss how most people could live to 95 in good health using lifestyle interventions we already know work. Dr. Eric Verdin is the CEO and President of the Buck Institute for Research on Aging, the world's first independent research institute focused solely on aging. He has published over 200 peer-reviewed papers and is internationally recognized for his research on immune system aging and epigenetic regulation. We Also Discuss: Why There Are No Proven Anti-Aging Supplements or Drugs for Humans Yet How Yamanaka Factors Can Reverse Aging by Reprogramming Cells Back to Youth The Discovery That Immune System Aging Controls Whole-Body Aging Why Your Blood Contains 600 Different Cell Types (Not the 12 You Learned About) How Lifestyle Factors Could Add 30 Years of Healthy Life for Most People The Problem With "Instagram Medicine" and Unproven NAD Infusions Why Brian Johnson's Self-Experimentation Matters Despite the Controversy The Coming Revolution in Precision Medicine and Digital Twins How Organ-Specific Aging Clocks Predict Your Individual Disease Risk Why the Brain and Immune System Are the Two Most Important Aging Targets Thank You for Our Sponsors: Try IM8 today with a 30-day money back guarantee. You can get 10% off your first order with code DRSHAH at https://im8health.com/discount/DRSHAH Learn more about Dr. Shah: Website: https://www.drshah.com/ Clinic: https://www.next-health.com/ Instagram: https://www.instagram.com/darshanshahmd/ Learn more about Dr. Eric Verdin: Instagram: https://www.instagram.com/ericverdin.buck/?hl=en Website: https://www.buckinstitute.org/

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 0:50Dr. Darshan Shah?

  The longevity industry has exploded with promises that seem too good to be true. Supplements claiming to add decades to your life, influencers selling anti-aging protocols, and technology entrepreneurs predicting that we're going to live to be 200 years old plus. But what does the actual science really say about extending human lifespan in all of these interventions? Today, you're going to hear from Dr. Eric Verdin. He is the CEO of the Buck Institute on Research for Aging. This is one of the world's first independent research institutes, fully focused on understanding how we age. He's a scientist, and he dives deep into the science to see what's real and what's not. We're going to cut through all the hype and examine what rigorous research actually shows about the longevity movement. We're going to explore groundbreaking discoveries

• 1:34Dr. Darshan Shah?

  like epigenetic reprogramming, and why your immune system might actually be the master controller of longevity. For two decades, Dr. Verdin has been at the forefront of aging research. He's published over 200 papers, and he leads one of the most prestigious aging research institutes in the world, which is the Buck Institute. He's dedicated his career to separating evidence-based interventions from what he calls Instagram medicine. His work on the immune system is particularly engaging, and his epigenetic regulation work is helping to rewrite our understanding of what it means to grow older. Join me to welcome Dr. Eric Verdin to the Extend Podcast.

• 2:17Dr. Darshan Shah?

  Eric, it is an incredible honor to have you on this podcast. Thank you so much for joining me today.

• 2:22Speaker 01

  My pleasure to be here.

• 2:24Dr. Darshan Shah?

  You are one of the foremost experts in the world, I would say, in the field of longevity. And I'm going to put that in quotes because I know we need to make some definitions of that term. I personally, when we were together in Cannes a few months ago, or a few weeks ago, I talked about the definition of longevity and how that's been really, I think that term is not what it used to be, or what maybe you and I envisioned it to be. And so I'd love to start there, Dr. Verdin. What do you think people get wrong when they think about this term longevity, or their own longevity?

• 2:58Speaker 01

  Well, we are in some way becoming the victim of our own success. No one talked about longevity 20 years ago. There have been dramatic changes in the science of aging. And as scientists, I think when we saw these changes 25 years ago, we thought, oh my God, it's going to be a sort of revolution, and we're going to change the course of humanity. And so it turns out that we were not the only one noticing this. And so the whole term of longevity today encompasses a whole field. And I've taken a view which goes from the extreme, the people who will tell you that we're going to live forever, to a group

• 3:39Speaker 01

  of people who say, no, we should just focus on health span. And I take a pretty comprehensive view of the field. I think everyone has a right to express themselves. I think one of the good news of what's happening today is the fact that there is a lot of interest in health. And that's what I take as the positive thing. That being said, as the leader of an organization that focuses on the science of aging, I try to stay grounded by the principles that animates the whole science enterprise, which is, we are evidence-based, we provide treatment or interventions that are proven. And if we don't have a proof, we actually work at getting them. So I tend to occupy a bit of a more conservative space within

• 4:24Speaker 01

  the longevity realm. But there's room for everybody. And I think it is an open civilization, so everyone can express what they want. But I feel that I have to stand for what science stands for.

• 4:36Dr. Darshan Shah?

  No, and that's why I love your voice in this conversation because I think recently, I think maybe it was Peter DeMandis that was there at the Buck Institute and you guys were having a conversation and I think there's, and we see this with organizations, I think there's an organization called the Revolution Against Aging or something like that. And a lot of times they focus on the, their view of the science is that our exponential growth in scientific discovery around computer chips and around computing can be applied directly to the science of the biology. And why can't we see exponential growth in our biological discovery? And how does that not translate into adding many years to our

• 5:21Dr. Darshan Shah?

  life? Longevity escape velocity is something that we hear a lot thrown around as well by Aubrey de Grey and other individuals. And I just wonder, how do you answer that question? You know, there's this kind of a black box of technological evolution that we haven't really applied, I think, in my view, effectively to longevity science yet. And where do you think that can potentially take us?

• 5:43Speaker 01

  Well, the good news is that there has been a revolution in our understanding of aging. It happened in the mid 90s, work of Cynthia Kenyon and Tom Johnson, Gary Ruffkin, and Lenny Garante, many others, have really changed our way in our understanding of the aging process. That is, it is a process that is in part driven by genes, which means that we can modulate it. And so, the promise of what was shown in animal models, of course, made everybody excited. You know, we can double the lifespan of many species using single mutations or using drugs. That being said, when you enter the realm of humans,

• 6:25Speaker 01

  there is a whole, what I call a barrier to entry. And this is why it's so difficult to develop drugs for humans, because if you're talking about a longevity drug or longevity intervention, one of the important considerations is safety.

• 6:40Speaker 01

  If you're going to give a drug to someone for the rest of their lives, you better be sure that you're not going to shorten their lives.

• 6:48Dr. Darshan Shah?

  Right.

• 6:48Speaker 01

  So, and, and you know, as you know, being a physician, I mean, doing research and clinical trials is hard. It's expensive. We, we know the history of drug development is littered with problems. And, and the public actually expects it from us to deliver, to recommend interventions that are safe.

• 7:09Dr. Darshan Shah?

  Right.

• 7:09Speaker 01

  Not always, but most of the time. And it's a very different situation if you're trying to cure someone from a cancer that is going to, to kill them within the next couple of years, where, you know, the barrier to entry is much lower and people are willing to take more risk. Than to take a 24-year-old who says, you know, I want to live as long as possible. Or even a 60-year-old who wants to live as long as possible to recommend something that is going to be safe and leading to the, the expected effect. So that, that would be my, so my philosophy is that we, the, the field of aging has entered a new stage, one where we are taking the, the science that has been shown in animal models

• 7:53Speaker 01

  and trying to bring it to humans. And I, I urge patience and some degree of conservatism because, and so my attitude has, has been essentially not, not to walk around and tell people, I'm going to live to 150 years old, because honestly, I do not think I will, but to really under-promise and over-deliver. And as you alluded to at the beginning, you know, the field has a bit of a mixed name because it turns out that a significant number of very visible people are doing exactly the opposite. They are over-promising and, and my prediction is that they will under-deliver. I will remind you, you know, early in 2000, the year 2000,

• 8:36Speaker 01

  a number of people in the field were claiming that we were going to live to 800. And they're not doing this anymore, thank God. Now they've replaced this to 150, which still sounds very exciting, but I don't think we're there yet. Last point is, It is, you know, I think it's Neils Bohr who said it's very difficult to make predictions, especially about the future. And we, you know, if you had told me fifty years ago that I would be walking around with a supercomputer in my pocket, that we would be having this call, that I would be accessible via video call anywhere in the world at any time. We were talking about this as sort of some kind of utopia.

• 9:21Speaker 01

  Now, all of this technology is there in large part due to science and physics and discovery. So it's very hard to predict what will happen in the future. The science has advanced enormously, but there are still really significant hurdles to conquer for us to really implement this increased longevity that everyone aspires to.

• 9:46Dr. Darshan Shah?

  Right, right. Such valid points. And, you know, you're there at the Buck Institute. I want to talk a little bit more about the Buck Institute in a minute, but I would, you know, you have your finger on the pulse of the science every day. Most of the science is being run through you. You're seeing a lot of the, a lot of the research that is coming out. What has surprised you in the last year that you've seen? Is anything really surprising that you've seen in the last year that has come out?

• 10:12Speaker 01

  Surprise, yeah, I mean, it made me very enthusiastic, which in some way moderates my conservatism. Sometime, you know, I come across as being very conservative and a naysayer, but I'm not. I'm as excited as anybody by what we are discovering, by what the speed at which the field is moving. You know, there's not a, I would say, not a month that goes by that I don't see a paper that excites me. So the science is amazing and it will undoubtedly change the way we age in the future. That would be, you know, that's pretty much where I am right now. So full of hope in terms of the future. Now, if you think about one discovery that I find as probably the most important in

• 10:57Speaker 01

  the last ten years would be this idea of epigenetic reprogramming. And if you're one, I can Speak a little bit about this, this idea that, you know, we, we are, our biology is driven by two processes. First is our genome, the codes in our, in our, in our DNA. That is inherited by you from both of your parents. It is fixed for life. It doesn't change unless you accumulate some mutations, which can lead to cancer. And every cell in your body has the same genetic material. So how, how is it that one cell becomes a heart cells, another one a neuron in the brain? It is through a process that we call epigenetics. It's another layer of control,

• 11:39Speaker 01

  which is at the level of the histone proteins and the DNA modifications. And this is a whole idea of epigenetics. So this regulation actually determines whether a cell becomes a neuron or a, a heart cells or muscle cells. And that regulation is actually a lot more plastic that, that we had anticipated. By plastic meaning we can modify it. And one of the ways in which we modify it is via lifestyle factors. So, I think it's Mike Rosin who says we are all genetic engineers. So when you go to exercise, at the end of your exercise, you are not the same person as you were before.

• 12:23Speaker 01

  A whole series of chemical reactions have taken place and, and you are now different. And so that's one of the ways in which we can really influence our longevity. One of the biggest discoveries is the idea that, um, two discoveries. One, we can measure this epigenetic changes. And this is the basis for what people refer to as these epigenetic clocks. So this is measuring the state of these modifications, which allow you to determine where you are in terms of your aging process, at least to some, some extent. And the other thing is we now have tools that allow us to modify the epigenome, this level of regulation. And it turns out if you reprogram your cells using

• 13:09Speaker 01

  Transcription factors, this is maybe a little technical. You can actually reverse the aging process. It turns out that epigenetics regulates cell identity, but also with aging it becomes somewhat loose. And so cells lose a little bit of their identity. Your red blood cells might look a little more like neurons and your muscle cells a little more like heart cells. And so this contributes to some part of the aging process. And we have discovered ways in the laboratory animals to actually reprogram the epigenetic landscape to make it younger. And it turns out that is our first evidence you can actually regress, revert the aging process.

• 13:52Speaker 01

  So this is actually pretty amazing if you think about it. At least it doesn't revert all of the changes of aging, but there's a very big part of it that we can revert in the laboratory setting. Now, the big question is how do you do this in humans? And a number of companies have been launched. I mean, the most visible is Altos, which aims to reprogram organs and tissues. There's a big mountain to climb and I think we probably will do this on individual organs or individual tissues first. But we all hope at some point you could actually reprogram the aging process in a whole individual. So that is one really exciting experiment.

• 14:35Speaker 01

  And we're working on this, in our cases, in the immune system, which is a highly relevant organ in terms of aging. And I hope we get a chance to discuss this. And one that is also highly accessible. So I have a hard time not to be optimistic and excited about what this holds for the future.

• 14:53Dr. Darshan Shah?

  Yeah, it's incredible. And you're referring, I think, to the Yamanaka factors and the ability to apply these basically four proteins to any cell and reverse the aging process and make a differentiated cell go all the way back in steps to an undifferentiated cell. Is that correct?

• 15:10Speaker 01

  Yes, so the Yamanaka, Shinya Yamanaka, who was one of my colleagues when I was still at the Gladstone in UCSF, is made an amazing discovery. You can take any cell in your body and you can reprogram it using these four Yamanaka factors and it will actually, and you can make it go all the way back to becoming an embryonic stem cells. And this goes to the point that you can actually take a muscle cell or a lymphoid cells from a mouse and you can recreate a whole new mouse from it. So you've erased all of the aging process. That new mouse lives a normal life. So you have managed to erase the whole aging process, which is pretty unbelievable if you think about it.

• 15:55Dr. Darshan Shah?

  It gives me chills just thinking about it every time. It's just, you know, four simple factors can achieve basically immortality that we found in a mouse, right? You can go all the way back to embryo and take this mouse and make a whole new mouse that is that lives a normal life. Is that correct?

• 16:11Speaker 01

  That was the genius of Shinya's discovery. He started with 250 factors and he was able to whittle it down to four, which actually do the job. Not one thing we should say is that this is occurring with an extremely low efficiency. Very few of the cells that receive the factors eventually make it. And we don't fully understand what is the process. Now, where this comes into aging is obviously we don't want to turn ourselves back into a puddle of embryonic stem cells. That would not really be helpful. But what Carlos Ipsisoua Belmonte at the Salk Institute discovered is if you do a partial reprogramming, that is you add these factors, the Yamanaka factors, and you don't allow the process to go all

• 16:56Speaker 01

  the way back to the stem cells, but you stop after a while so that you have not really completely changed the identity of the tissue, and then you allow it to relax back into its normal state, the cells are rejuvenated. So that is pretty far off, pretty cool. My only regret there is that I'm not the one who did the experiment because it was pretty ground shifting. And frankly, it shows us that the aging process, at least part of it, and that is important to realize, is part of it can be reverted.

• 17:31Dr. Darshan Shah?

  Right. You know, I'm curious, though, you know, you look at the aging process that is in stem cells and as stem cells divide and they go through their divisions, they accumulate damage, they accumulate DNA damage over time and then that DNA damage is passed on to the next division of stem cells. How does a Yamanaka factors come in and reverse the damage as well in a particular stem cell? Is there any thoughts around those mechanisms?

• 17:57Speaker 01

  It's a good question is, you know, and that's one area that Manav is studying. What is the effect of the accumulation of these mutations? Because eventually, if you accumulate enough of them, by the way, they are not corrected by the Yamanaka factor. The Yamanaka factor does not modify the sequence of the DNA. What it means is that most of these mutations that do accumulate during aging, and we have some evidence, they do accumulate in the immune system in every tissue slowly over time. Eventually, you know, are going to be a very significant barrier if we envisage that we're going to live, you know, 500 years.

• 18:37Speaker 01

  So the accumulation of these mutations is still very hotly debated on what role they do play in the aging process. Clearly, in the case of cancer, they do play a role. In terms of aging, it's still not totally clear. But my prediction is that when they will accumulate beyond a certain threshold, they will start hitting, imagine the genome as 3 billion base pairs. Some of it is referred to as junk DNA, which in part reflects the fact that we don't understand what it's doing. A lot of these mutations are so-called silent mutations. That is, they do not affect a gene or a protein and therefore do not have really significant consequences.

• 19:18Speaker 01

  But for the long term, it will be a problem because these mutations are random. And so identifying every single one of them and correcting every single one of them is going to be an almost Herculean task. And I cannot, at this point, no one really has any idea of how we're going to deal with this problem.

• 19:36Dr. Darshan Shah?

  Right. But to your point, though, you know, this could be extremely useful clinically in cases where we need organ regeneration. Like, for example, I have a friend who's now suffering, you know, he had liver failure due to Nash and alcohol, and he got a liver transplant. And that was the only treatment left for him was a liver transplant. However, I do see a world like where you're saying, like, for organ-specific regeneration for him, instead of going through a massive surgery and needing all of this immunosuppressive medication, a therapy involving amenaka factors that can take the remaining liver stem cells and create new liver tissue would be a game changer for the medical community.

• 20:16Speaker 01

  Clearly, and there is an enormous amount of research that is being done exactly in this direction. Now that we can take, for example, you would not even need to take the liver. You could imagine someone has liver failure, you would isolate blood cells from that person, you would revert them into embryonic stem cells, and then from the embryonic stem cells, you would differentiate them in the lab in liver cells. And so, we now know how to, starting from an embryonic stem cells, which we call pluripotent, because they have the potential to become anything, there are many protocols that allow us to take these embryonic stem cells, especially in mouse, and to differentiate them into

• 21:01Speaker 01

  any specific cell type. So, the idea of tissue regeneration is going to be key in the future. Because there are two aspects to aging. One, there's preventing the damage that occurs and that is part of the aging process. And that's, you know, quite often, you know, what we focus on is lifestyle factors, which are extremely powerful. And second, once an organ has failed, and we all have some frailty point, which means that all of our organs don't age at the same rate. Some people have an aging heart, some people have an aging brain, some others, it's the immune system. So, the idea is that you would identify... Which of your tissue is your first D point?

• 21:45Speaker 01

  Which one is the most likely to fail? And then induce specific regeneration of that tissue? So this is where the field is going. But it's going to be quite a few years before we get there.

• 21:57Dr. Darshan Shah?

  Yeah, it's just incredible though to think about what the future holds there because it is possible in a lab already. And so it's just mind blowing to think where it's going.

• 22:09Dr. Darshan Shah?

  Hi, Dr. Shaw here. I want to take a minute to talk to you about cellular health. So in my clinics, I've actually seen 30 year old people with cells that look like they're pushing retirement. And I've also seen 60 year olds with cells that look like they're 40 years old. So what's the difference? It's really about how fast their telomeres are breaking down. Your cells you see are like phones and they have limited cell phone battery. Poor sleep, stress, processed foods, all of these things can drain that battery way faster than it should. So this is the reason why I partnered with IMA. IMA powers that cellular battery. It's not just another multivitamin. It's a comprehensive 92 ingredient formula designed specifically for cellular health and longevity.

• 22:54Dr. Darshan Shah?

  I'm talking 900 milligrams of vitamin C. That's like 20 oranges worth of DNA protection. The clinical dose of CoQ10 that you need to power your cellular engine. You also get zinc, selenium, vitamin E, alpha lipoic acid. All of these work synergistically for cellular repair and protecting your telomeres. So instead of taking a handful of pills every day and all these supplements, IMA actually gives you everything that you need in one scientifically formulated system. And this isn't just a theory anymore. IMA had partnered with Oxford University, the International Space Station, San Francisco Research Institute, and they've done studies and they've gotten this NSF certified to truly power your health. Most people are aging twice as fast as they should, unfortunately.

• 23:40Dr. Darshan Shah?

  You don't have to be one of them. Try IMA. I actually have a discount secured for you. If you go to drshah.com/ima or go to imathhealth.com/discount/drsah and you can get 20% off with my discount code, Dr. Shaw. You can also find the link below.

• 24:01Dr. Darshan Shah?

  You alluded a couple of times already to the immune system and I really, I would love to dive into this. You said a couple of things. Number one, aging kind of starts, the immune system is one of the fundamental reasons where we age, or some fundamental areas where we age, immunaging, immunosenescence. And also you said it's the most accessible. And I assume you mean, you know, through a simple blood draw, we can pull out obviously white blood cells and immune cells. And really, if you look at the, everything that lives in the blood, the, where you're going to get the most DNA is through your immune cells to go into a process like you're describing where you can maybe turn this cell around and go into a pluripotential stem cell. And I'd love for you to talk a little bit more

• 24:43Dr. Darshan Shah?

  about the accessibility of the immune system and why you've targeted that in particular at the Buck Institute and through your research. And how does immune aging lead to all the other forms of aging that we see in our biology?

• 24:57Speaker 01

  So I want to tell you two stories that, both recent. So I started, I studied immunology for many years. So for me, this was my area of specialization. And so when I, when I came to the Buck and I had to really think about what is my lab going to be focusing on, I was a bit tired of what I was doing before. So I thought, okay, let's just define a new program. I decided to focus on immune aging. And at the time, the thinking was, there is a process called immune aging, which is, or inflammaging, which is this idea that as we age, our bodies become chronically inflamed. And this is thought to be not only a consequence of aging, but also eventually a cause. So the inflammatory reaction is

• 25:42Speaker 01

  a protective response that our bodies have to injury. And so as you accumulate damage and injuries in your body, your immune system responds and tries to fix things. And, and it does this quite well. Just imagine if you cut yourself, or if you burn yourself, you will have a whole series of inflammatory responses. And we're all familiar with this. First, it will get red if you get burned, then there will be a bubble, eventually a scar, a crust, and eventually this will Fall off and there will be no, no trace of what happened. So this is inflammation at work. So it's an incredibly important process that helps us to heal and repair. And so we are imbued with all of these repair mechanisms, which is an incredible gift, uh, which allows us to, to survive.

• 26:25Speaker 01

  The problem is that during aging, the damage accumulates to such an extent that the body cannot deal with it. And, and so you have a chronic state of inflammation. The problem, you, you might think, well, this should help to solve the problem, but it doesn't. Because the, the system becomes essentially overwhelmed. And what's quite interesting is that the inflammation, the chronic inflammation versus acute inflammation becomes a problem by itself and it contributes to the development of all of these diseases of aging. So, so that, that's the first point. That, that's how I got started. Yeah. But since then, I would say three stories, uh, two, two big stories have emerged that I think have comforted me

• 27:09Speaker 01

  in the idea that studying immune aging is important in the field. The first one was the realization in mouse tissues, again, this is experiments conducted in mice. If you induce a lesion only in the immune system, and we can do this using genetic tricks. That is, we can, for example, replace the immune system with a new immune system that has a mutation. So that only the immune system ages at an accelerated rate. Okay. So there's technology in mice that allows you to do this, the so-called pre-lox type of technology. Okay. Two studies have reported, if you do this, you induce an immune-specific lesion, you find out that the whole organism ages faster.

• 27:53Speaker 01

  And so that was really puzzling. And so it speaks to one unique property of the immune system is that it is a distributed organ. When we think immune system, you probably think about your tonsils or your spleen or your thymus or your lymph nodes. But it turns out every one of our tissues has immune cells. They constantly patrol every tissue to check for damage, to, to. Repair and so on. And so what was remarkable in these studies where the immune specific modification was made is that every tissue aged faster. And so that indicates that if you if you have an aging immune system, you're going to see organismal aging.

• 28:35Speaker 01

  And that means also that by fixing the immune system, hopefully you could solve the whole problem. So that that was one of the the reason. Uh, the second big observation is a paper that was published by my colleague, Tony Wiskorey at Stanford. And this led to the creation of a company, by the way, called Vero on the border, which I sit, which I think is really exciting technology. So what Tony observed is simply by measuring the abundance, the relative abundance of a series of proteins in the blood. He is able to predict and determine the rate of aging in individual organs. Okay. So if you you're probably familiar, if you have a heart attack. Yeah.

• 29:18Speaker 01

  The the heart cells get damaged, they release a protein called trophymycin. But you can measure in the blood and it's actually a diagnosis for that's a a criteria for diagnosing a heart attack. Right. But he essentially did this for every tissue. He identified unique proteins to the brain, to the immune system, to every organ. And by measuring them on the blood, he can assess the state of health of individual organs. Ah. Now, they were able to, we just, they just published a paper a couple of months ago in Nature of Medicine. Uh, where they went back to the UK Biobank, this very large uh cohort of of people in England that have been followed for years. I was able to get blood samples from, uh, I think forty five thousand of them.

• 30:03Speaker 01

  And then to actually start asking very simple question, what do these organ specific clock measure? Are they predictive of a long lifespan? Which organ is the most important in terms of uh maintaining health? And they identified two organs that were the most predictive of your life expectancy. And these were the brain and any immune system. And I would say not surprisingly. Again, because the these two organs, the the brain and the immune system are both distributed. When you have a lesion in your brain, because the brain is essentially regulating, think about it as the supercomputer of the body, regulates the activity of every cell.

• 30:45Speaker 01

  So some brain lesions will disturb how your liver works. And so really identifying these two organs as the one, the most important that you should focus on maintaining your health, I think is is another landmark study.

• 31:00Dr. Darshan Shah?

  Yeah, this is so interesting because, you know, when I think back on medical school and I think what was the most complicated subjects I had? It was always immunology and neurology.

• 31:12Dr. Darshan Shah?

  The level of complexity of the brain anatomically, physiologically and the immune system is mind blowing. Like relatively the liver, the heart, the kidneys are like child's play.

• 31:23Speaker 01

  And I'll tell you another example, you know, I you probably went to medical school, you know, a little bit after me and and when I was in medical school, you know, there were lymphoid cells, there were neutrophils, eosinophils, and maybe maybe half a dozen cell types that you could actually measure in the blood. With the technology that we have today, in my lab, we can enumerate more than 600 different cell types in the blood, which just gives you an idea of the complexity. So the more sophisticated our tools are becoming, the more we realize what we don't know and and what we have to learn. But out of every one of these discoveries comes, you know,

• 32:07Speaker 01

  new opportunities to intervene, to understand and to really refine our understanding of the aging process.

• 32:13Dr. Darshan Shah?

  And that just blows my mind that, you know, we're taught in immunology classes in medical school and even as physicians that there's basically like 10 to 12 different cell types in the immune system. And you're saying there's 600 actual different cell types.

• 32:26Speaker 01

  Just in the blood, it doesn't speak to all of the. T cell macrophage subsets that are lurking in every one of our organs. And you know, we know the immune cells in your gut are different from the ones in your brain, different from the ones in the various tissues. So, yes, we are, you know, we live through extraordinary times where we have the technology to really probe deeper and deeper. And I make the analogy to the new telescopes, you know? We used to think there were so many billion galaxies and every time we get a new telescope, we realize, you know, there's another, you know, billions of billions more of galaxies.

• 33:09Speaker 01

  So, and the same thing for biology, the more precise, the more deeply we look, the more we realize the incredible complexity. And our human organism is fourteen trillion cells. And therein lies some of the, what we see with the tech people. And I'm not saying this to pass judgment on them, but there's a little bit of a misunderstanding in terms of, you know, moving from the tech world where you control everything, you understand everything, after all, you have written the algorithm, you can go look at the code. Moving into a system like the human body with fourteen trillion independent entities,

• 33:50Speaker 01

  each of these cells has more than a billion chemical reaction every second. So you just get into a world of such complexity that I ask for some degree of understanding and forgiveness for the slowness by which we discovering heroes, but it is incredibly complex. And, and, and, you know, we do not have, we are far from the full understanding of what biology is, what an organ is, how they interact and all of this. Making rapid progress, certainly, and all of this accelerated by AI, but still, I, I think we should be realistic when we look at the complexity of what we're dealing with, that there are no magic answers, there are no magic bullets.

• 34:34Speaker 01

  The only thing that's going to happen is a continued investigation, understanding, and all this driven by, you know, by science. And by, you know, accepting your defeat, revising your models, this is what science is all about, is, is full of uncertainty. This is the essence of, of what doing science is, is you always try to find a better way to describe what you're observing.

• 34:59Dr. Darshan Shah?

  Yeah, that's such a beautiful analogy there, Eric, where you say, you know, every time we have a telescope, we discover billions more galaxies and never do we say that we are going to enumerate every planet and star in the universe. We never say that. No matter how much technology we have, that we don't say we're going to go out there and catalog every one of these celestial bodies. Why do we think we're going to figure out biology way before we're going to figure out the universe? Right? You think about Star Trek and how that's a never-ending journey for those people. The biology can also be a never-ending journey. It's that incredibly complex.

• 35:36Speaker 01

  You know, our model is to, I mean, for everyone, is to be able to write a code that would simulate the body. And this is actually, for the first time, these what we call digital twins. And we have a big program here at the Buck doing this, which is the idea to actually modelize a whole, first a living cell. This work is being done right now by some of my colleagues here at the Buck using bacteria, which are the very, very, very simple organisms. And even there, it is extremely hard to do. Now, thinking about doing this for humans, we are also taking these steps, building these models. And in some cases, they can be highly predictive.

• 36:20Speaker 01

  And that is a really exciting new area. So we are entering an area where we can modelize the human body, but I should say, some degree of humidity, we are just taking really baby steps. But they will be the future. You know, one of the, as a physician, you probably are, you know, acutely aware of the difficulties of conducting clinical trials or making recommendations for people in terms of their health. We call this the N of one analyzes, this idea that we are all highly individual and different. We respond to drugs in different ways. And the reason why we, clinical trials are so expensive

• 37:02Speaker 01

  is because we're dealing with an incredible diversity of genetic materials, lifestyle, and so on. So. The way we do clinical trials is to take 50,000 people, we give them the drug, we look, we separate them in two groups, 25,000 have the drug, 25,000 don't have the drug, and then we compare. And if we find any kind of signature of difference, even if, you know, 500 people show an improved response in the group with the drug, the drug is approved. What about the 44,500 people who did not respond? What happened to them? We have no idea. And so this is the impetus behind this trying to modelize biology is to be able to much better predict what happens

• 37:46Speaker 01

  without going through an expensive clinical trials or putting people at risk who don't need to be put at risk. So that, you know, even though I started by saying the task in front of us is enormous, it doesn't mean that we should not be trying. And, you know, the buck is really leading the way in trying to devise what we call precision medicine, this idea that whatever is good for you is not necessarily good for me and it can actually harm me.

• 38:15Dr. Darshan Shah?

  Yeah. Yeah. In fact, right now, Eric, I'm writing a book called N of One. And just for my patients that need a clinical model to utilize this thought process, it's so important because like you said, you know, everyone fits somewhere in the bell shaped curve. The problem is, we don't know where you fit on that bell shaped curve. And until we can model biology in a computer, which as you alluded to, is going to take us a very long time, I think is important for humans and people trying to get their health right to use these N of One experiments on themselves, have some data to track and follow and see what's working and not working. And you just keep self experimenting until you find a combination of lifestyle factors and other interventions that work for you.

• 38:58Speaker 01

  Yeah, two great points. And then one that I can amplify in two different ways. One is Brian Johnson, you know, who is being condemned by some people in our field as being sort of a attention seeker, whatever. I disagree with this. I think what Brian has done is incredibly important in a way that he has done, you know, the highest level of self experimentation that we can imagine. I mean, he tests himself very regularly, changes interventions and so on. And he's Been able to identify a whole series of factors, lifestyle, drugs and interventions that do actually work for him. I do not doubt this. I mean, his numbers look pretty impressive.

• 39:43Speaker 01

  That being said, they work very well for Brian Johnson. The big question in the field is, will it work for me? And this is where his approach is falling short. So I think the value of what he's brought is to essentially show us the way in which we could do this on an individual basis. The shortfall is that, you know, a whole bunch of people are buying these supplements without any guarantee that it actually is going to work for them. And my prediction is that it most likely will not. So that being said, for us as a field, it points to a way of practicing medicine, not on a population basis, which is the way medicine is pretty much functioning.

• 40:27Speaker 01

  We do, as I described earlier, we do these large clinical trials. But by really going to the individual and testing in each person, different interventions, and I'm sure there are going to be some shared interventions that will work for most people, but there are also likely to be significant differences. And so the idea is, how can you identify these differences? How can you model them? And how can you actually identify what is the best protocol for you versus me or versus your patients? So this is where the challenge lies in the future.

• 41:02Dr. Darshan Shah?

  Exactly. It's a beautiful place to be, though, because if we didn't have this, if we weren't enabled right now to really go deeper into this N of one model, using computation and also just a thought process, we'd still be stuck in kind of an archaic field of medicine where we're doing, relying on large-scale randomized controlled trials that take forever to do and are incredibly complicated and expensive to make any headway. And I think we, like you mentioned earlier, we are in an incredible moment in time where that model is changing.

• 41:34Speaker 01

  Could not be a better time to... People ask me, you know, "When are you going to retire?" I think I'm at retirement age and I tell them, I think when they take me away and they say, "If you consider retiring," if someone tells me this, I will take that very seriously. But could not be a better time and a more exciting time to be a physician, especially at the cutting edge of research. I think we are in the process of rewriting medicine. And it's always hard to see when you're in the middle of a revolution. But I'm, you know, having been in this business for now more than, let me see, I hate to count, more than 40 years, I've never felt so much excitement and optimism about the future,

• 42:18Speaker 01

  about the form of medicine that we will have 20, 30, 40 years from now. It's going to be transformative.

• 42:25Dr. Darshan Shah?

  I agree with you, Eric. And, you know, I have Next Health in our clinics that we're really trying to create a distribution model where people can go to a clinic in their local city and maybe have not just these thoughts about end of one medicine, but also when new technologies, new therapies come out, we can rapidly bring them to the people. And I think, just like you, I wake up every single day just excited and motivated to be a physician in this moment in time. And just being part of this, a small part of this change, of which, you know, you're also kind of leading there at the Buck Institute. And I'm excited to be working on this with you and alongside you. I would love to kind of end our short time that we had together.

• 43:09Speaker 01

  It went way too fast.

• 43:10Dr. Darshan Shah?

  I know.

• 43:11Speaker 01

  We were just getting started.

• 43:13Dr. Darshan Shah?

  Right, right. I'm hoping you would please grace me with one more conversation in the next few months. I'd love to dive in on some topics. I have a whole list of topics I wanted to dive in with you. So hopefully we can have you back.

• 43:24Speaker 01

  With great pleasure. Love talking to you.

• 43:27Dr. Darshan Shah?

  I love it. I would love to just kind of end this podcast on some of these shared interventions that you really believe in, that you utilize yourself, that you think most people listening to this podcast could really move the needle with modifying their epigenetics and just adding more health span to their lifespan at this point in time. You're an incredibly healthy individual yourself. You look incredible. And I would love for you to give us a few of the top, maybe three to five interventions you think would work for most people out there.

• 43:54Speaker 01

  I'll make two points. The first one is, it's gonna sound pretty harsh, but it's the reality. There are no supplements and no drugs in humans today that are known to safely increase health span or lifespan. Okay, so that the data is just not there. We're working on it. We're working on, we're doing clinical trials with drugs. So this is all ongoing. So if you choose to go on a supplement or on a drug, you're taking some degree of risk. And so it might work for you or it might not. We will not know for another five to 10 years. Many of the early candidates are being tested right now.

• 44:35Speaker 01

  That being said, there are a number of things that I do and test. And because I consider it part of my job, so I do, you know, I'm sort of a Brian Johnson in my own right. In a way, I do a lot of self-testing. I do experiment with different drugs and I try to see what is the effect on my body. And I measure, and some of them frankly, don't work and some of them actually do seem to work. So they, I don't mean to be saying that you should not be taking anything, but you should do it with the support of a physician. Someone that actually knows how to look at your biology. And I'm worried about what I call Instagram medicine, which essentially, you know, a supplement gets touted with great enthusiasm.

• 45:18Speaker 01

  Sometimes I'm dumbfounded by how our science actually gets translated into Instagram medicine. And sometimes with horror because it just, there's no basis or, you know, the whole intravenous NAD is the latest one. Just doesn't make any sense from. A biological standpoint. And so before you get that N A D infusion, I think, think twice, read about it, or maybe talk to the people who work on N A D, such as me in my lab, just doesn't make any sense. So, so that that's one aspect. The second aspect is, we do know what increases health span and lifespan today. And the best we have is lifestyle factors. Now, someone is going to say, well, I know, my grandmother told me, and then, you know,

• 46:02Speaker 01

  I should be eating well, I should exercise, I should sleep, I should decrease stress, I should have human connections. These are all the factors that determine uh uh health span and in some degree of lifespan. Today, based on what we know, most of us could expect to live to ninety five in good health. Now, as you know, this is very different from the reality where most people in the U S live in good health until age sixty five. So there's thirty years of extra life that most people, unless you have an accident or you carry some kind of mutation that puts you at risk, most of us could live to ninety five in good health. So that is, to me, that's already absolutely incredible.

• 46:43Speaker 01

  And I would urge your audience to really, you know, inquire, what are these factors? How do I apply them? Because this extra thirty years that you're going to gain is going to give you, is going to give us the time to bring up the next generation. So, you know, people think, uh, some people have argued that I'm talking too much about health span uh and and and lifestyle modification. I I do it because I think this is proven to work. So we know if you do this, the response is going to follow. And that will give you an extra thirty years to benefit from what science is going to bring in the next thirty years. That would be my um my advice for people.

• 47:26Speaker 01

  Rather than jumping on the next Instagram uh sort of fad, just really focus really hard on what is available today, what does the science say? Now, in this respect, there's also a lot that still is unknown. When we're talking about exercise, you know, people quite often will ask, what form of exercise? Should I run? Should I jog? Should I row? Should I do high intensity interval training? In what proportion? Should I do balance? Should I do yoga? Right now, my philosophy is that I try to do a little bit of all of them, because we do not fully know which ones lead to the longer life. That is also being studied using the tools, the most modern tools that we have.

• 48:11Speaker 01

  This is a whole concept that Lee Hood and Nathan Price, who are two faculty at the back, have advanced in their book. It's called The Science of Wellness. Now, if you haven't read it, I encourage you to read it. It's a remarkable book, saying that wellness is not just fluff. Wellness is this idea that your lifestyle factors can dramatically influence your health and your life expectancy. The question is, how does that happen? Exercise is an incredibly powerful anti-aging intervention that we have available today, but we need to study it better. We need to understand what are the modalities. We're all busy. You know, we don't know really how much we need to exercise. We don't know in what proportion between the different forms and so on.

• 48:54Speaker 01

  So these are all incredibly important questions. Same thing about your diet. The science of nutrition is somewhat confused right now. You know, I have proliferation of all these diets, paleo diet, keto diet, Mediterranean diet. Which one is the best? Same thing for sleep, same thing for human connections. All of these are incredibly important. And right now, I'm passionate about those for my own life, because I really have benefited and I see the results in terms of how I feel and my energy and so on. But imagine this distributed at the scale of the country.

• 49:32Dr. Darshan Shah?

  Right.

• 49:33Speaker 01

  And the dramatic effect it could have on the population health globally. So I am passionate about this, as passionate as I am about, you know, pushing the envelope and going deeper and deeper in our understanding of biology and inventing the next generation of medicine against aging.

• 49:53Dr. Darshan Shah?

  Yeah, I love that. And I think we're on the right path together with your sage advice. And we look forward to following you very closely with what you're doing at the Buck. I think you're definitely leading the charge here to maybe finding that intervention. But to your point, we can get another 30 years of health span, which is even, I would argue, even better than having a 30 years of lifespan where you're not healthy. Because then you have to live, you know, in a wheelchair. You have to live not recognizing your friends and families. So the focus should be in getting that 30 years of health span. And I appreciate everything you're putting out there, Eric. Thank you so much for joining me today.

• 50:30Speaker 01

  Yeah, I'll make one last point.

• 50:32Dr. Darshan Shah?

  Please.

• 50:33Speaker 01

  Which is when, when I got this job, I felt, okay, this is a unique position in terms of being able to, one of the leaders, to be one of the leaders of the field. And people are going to listen to you. And I should be able to speak of personal experience. And of course, we all want to live long and healthy and happy with our families and our friends. That's, that's the universal goal. Everybody wants this. The, the issue is how do you get there? And I, as I went through this journey of optimizing my health, the original impetus was, you know, can I live long and keep doing this great job? Or having this fun job for as long as possible.

• 51:16Speaker 01

  But what I've come to realize is I'm doing it is that in the process, I feel better. I have more energy. And so in some, I don't even think about my own longevity, frankly. I, I think about the fact that right now, I think I'm optimized. I'm feeling the best that I have my whole entire life, which seems hard to, to believe. Some people don't believe me, but I, I think it is true. I have more energy, more, more focus and so on. And this is a result of meeting what I would call an optimized sort of lifestyle. And I think this is where, you know, this is sort of the whole Buddhist, Buddhist principle of, you know, here and now, and, and which is really where you reap the benefits from an immediate point of view.

• 52:00Speaker 01

  You know, if I end up living longer, wonderful. But I also know that I feel the best that I could possibly be right now. And I think on this, I think I hope, hopefully this will encourage some of your listeners to actually engage in this journey.

• 52:16Dr. Darshan Shah?

  Yeah, feel better now. Exactly.

• 52:19Dr. Darshan Shah?

  Eric, where can people find you and hear more from you?

• 52:21Speaker 01

  Well, you can find us, you know, the Buck Institute has a pretty busy website with lots of opportunities to engage with us, to learn. We have classes. We have, if you're located in the San Francisco Bay area, we have community seminars. I'm a lot on LinkedIn, which I think has emerged as a great platform for us scientists to actually convey some of our findings to the public. It's a little more elaborate than X, or you can actually expand on ideas. I find LinkedIn great. I also dabble on Instagram, but I'm still an amateur at this. I need a lot of help from my daughter.

• 53:01Dr. Darshan Shah?

  I love it. I love it. Eric, thank you from the bottom of my heart. Can't wait to have you on again. We're going to dive in more topics, more specifics next time around with you, and I appreciate the work you do. Thank you.

• 53:13Speaker 01

  Thank you for having me. I really enjoyed it.

• 53:16Dr. Darshan Shah?

  Fantastic.

• 53:20Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you liked this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best, and it's always important to seek their guidance.