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Dr. Tony Wyss-Coray on Huberman Lab: How blood resets aging

Parabiosis cut inflammation in aged mice via young blood factors; blood protein panels now assign organ age gaps that predict disease risk years before.

Dr. Tony Wyss-CorayguestAndrew Hubermanhost
Feb 23, 20261h 59mWatch on YouTube ↗

EVERY SPOKEN WORD

  1. 0:00 – 3:00

    Tony Wyss-Coray

    1. TW

      For the first time, we could take an old brain, and we could give factors from a young organism and ask, "Is that going to change the age of the brain?" And that's indeed what it did. So we saw that, uh, there are stem cells in the brain of these mice, that they got reactivated. There was less inflammation, more activity, um, that we can measure in the brain. And then most importantly, we actually saw that their memory function improved.

    2. AH

      [upbeat music] Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Tony Wyss-Coray. Dr. Tony Wyss-Coray is a professor of neurology at Stanford School of Medicine and an expert in identifying factors that can help prevent and reverse organ degeneration and aging. Today, we discuss the factors that are present in young blood, yes, you heard that right, and the factors that are present in blood after exercise that have been shown to rejuvenate the brain and other tissues in older individuals. Dr. Tony Wyss-Coray's lab has discovered several proteins that are present in high amounts when we are young and that circulate in the blood and that diminish with age, and if these are supplied to the aged body and brain, can reverse key features of aging, including improved cognition, tissue recovery from stress, damage, and more. We also discuss how aging is nonlinear. It does not progress uniformly across the lifespan. And we discuss the fact that there are certain phases, such as puberty, your early 40s, and your early 60s, when aging is accelerated and then slows again. We also discuss how different organs in your body age at different rates and how you can measure that. Today's discussion is a very important one because so often these days we hear about anti-aging and longevity, but today you're going to hear about the real science of organ rejuvenation. We also are going to talk about the role of sunlight, fasting, hormones, and the use of specific molecular approaches to improve your vitality and health. We also, of course, discuss exercise and social interactions, but in the context of the specific molecules they release into your blood to promote and enhance health, and how you can leverage that information. Tony Wyss-Coray is a celebrated pioneer in the science of these topics because of the rigor he applies to the work. He's not just talking about some molecule that someday there'll be a drug or some activity that we already know promotes health. He's an avid tool developer for measuring and reversing aging. So today we discuss all of that, and you're sure to come away from the discussion with both tools to improve your immediate and long-term health, as well as a deeper understanding of the biology. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Tony

  2. 3:00 – 6:35

    Young vs Old Animals, Age-Related Disease

    1. AH

      Wyss-Coray. Dr. Tony Wyss-Coray, welcome.

    2. TW

      Thank you.

    3. AH

      Great to see another Stanford colleague here.

    4. TW

      Yeah.

    5. AH

      You're a true pioneer. Your work is the first work that I heard of where somebody did a serious experiment taking blood from a younger organism, putting it into an older organism, and observing very interesting things. If you would, could you tell us about that experiment and what, if anything, has been done in humans to examine whether young blood, such a loaded term, but young blood can be a rejuvenation factor for the more mature body or brain?

    6. TW

      Yeah. So we were actually not the first ones.

    7. AH

      Ah, okay.

    8. TW

      Um, but we collaborated with, um, the person who in sort of, in more modern times, uh, used this model again. It's called parabiosis, where, um, you have a surgical model where an old and a young mouse are paired, and their circulation allows for exchange of blood from the young to the old animal. And my, my colleague, who, uh, recruited me actually to Stanford, Tom Rando, used this model to study aging of stem cells in the muscle. So he discovered that with old age, the muscle sort of deteriorates and, and doesn't regenerate. And when he used a mouse, an old mouse, and paired it with a young mouse, and then now this young circulation, um, infusing, if you will, the old muscle, he regenerated that muscle, and, um, it looked almost like a young muscle.

    9. AH

      Mm.

    10. TW

      Uh, and at the same time, he also observed effects in other tissues, including in the brain, and that's when we started to collaborate, um, and, and explored, uh, what could the effects of the brain, uh, of, of young factors on the brain, uh, be? And in part, we were also intrigued by that because we had separate studies in humans where we tried to find blood signatures of Alzheimer's disease, and what we noticed is that we could see proteins that were correlated or even predictive of Alzheimer's disease, but the most striking difference was between younger and older people.

    11. AH

      Mm.

    12. TW

      So we saw that the concentration of their proteins was very different in young people and old people. And when you see something like that in biology, you always ask, "Is this cause or effect?" So do the proteins in our body change because they respond to the aging of the brain, for example, or do they actually drive the aging of the brain? And here, Tom had this model that allowed him to ask that question or that allowed us together to ask that question, because for the first time, we could take an old brain, and we could give factors from a young organism and ask, "Is that going to change the age of the brain?" And that's indeed what it did. So we saw that, uh, there are stem cells in the brain of these mice, that they got reactivated. There was less inflammation, more activity, um, that we can measure in the brain with, um, electrical activity of neurons, and then most importantly, we actually saw that their memory function improved.... And so to your question, is that relevant for humans? We actually try to translate that, and we can talk more about this, where that, the stage of that field is right now to see whether that can be translated.

  3. 6:35 – 12:50

    Blood Biomarkers, Young vs Old Humans, Alzheimer's Disease

    1. AH

      Yeah, I would love to hear more about that. I, um, realize in your description that most of us think about blood, of course, delivering oxygen and red blood cells, et cetera, et cetera, but of blood that's drawn as a good, n- not the only, but a good window into the health status, the age status of a, of an organism, including us. But what I'm hearing is that it's also delivering nutrients or proteins of some kind that can reverse some sort of clock, and we'll get into later-

    2. TW

      Mm-hmm. Yeah

    3. AH

      ... whether or not it's an organ-specific clock or a body-wide clock. But I think, um, blood-borne factors, generally, I think of as a readout, not, um, as a medicine.

    4. TW

      Yeah.

    5. AH

      But you're talking about blood-borne factors as medicine.

    6. TW

      Yeah. I think that's really the fascinating aspect of, of, of, of, of this work that over the past few years, people started to look at, that many of these, uh, proteins and probably other molecules in the blood, they're not just reflecting the status of the, of the body, if you will, but they're actively influencing how it works, and the composition changes dramatically from young to old. We have this picture that I always like to show when I give a, a, a talk about our work, where we have, um, several thousand individuals, and we measure 3,000 proteins in them, and then we use colors to show low levels or high levels of proteins, and you see this dramatic change from young people to old people in a way, uh, that you can pick one sample, and you can say, "This person must be about that old," and we can talk more about what people call clocks. But to your question, yes, there are factors in the blood that clearly can change the function of cells and organs. And what the field is trying to figure out is what are the key ones, which ones could we use to slow down aging or to keep the body healthy as long as you live?

    7. AH

      So what has been done in humans in terms of a, an equivalent or pseudo-equivalent experiment to the parabios experiment you described?

    8. TW

      To try to translate that, um, we started a company, Alkahest, um, to, to see whether factors from the blood of individuals could influence, first of all, aging of a mouse brain. So we took blood from young people or old people and injected it into mouse brains, and we could show that young blood, um, could, in fact, mimic the effects of young mouse blood. So there were this similar factors in humans as in mice. And then we went a step further and worked, uh, collaborated very closely with a company, um, called Grifols, who is producing clinical medicines, um, for, for hospitals based on plasma donations. So they have centers where volunteers donate plasma, and then they pool this, and they isolate, uh, for example, antibodies. So if you're immunodeficient or you had cancer therapy and you, you are, uh, immunosuppressed, you will get regular infusions of antibodies that are sourced from healthy people, from these volunteers. Also, if you lose a lot of blood, you may get albumin, which is the main protein in our blood. So this company had this manufacturing process where they collect thousands of donations, and they process it into different medicines, and this allowed us to test these different fractions and see which ones have an effect in the mice. And again, we could find some of them that really were more powerful than others. And so we started some clinical trials in patients with Alzheimer's disease and Parkinson's disease and infused them with these fractions that we've shown, uh, have, uh, effects in mice. And these were small trials, but they looked promising, and they're related to what people have been observing previously, that if you get, uh, blood transfusions, often people have sort of-- feel invigorated, or their mind, they say their mind got cleared or they, they improved. And this company, actually, Grifols, had also run a clinical study that was blinded, placebo-controlled in patients with Alzheimer's disease, where they first removed their plasma, this is called therapeutic plasma exchange, and then infused them back with, um, a major blood component, this albumin, which also contains other factors, and they saw clear, significant benefits, and this was in 500 patients. So the field is trying to figure out next steps and hopefully do really one of these large clinical studies where you can then say, "This actually works and could get FDA approval."

    9. AH

      Have you done one of these?

    10. TW

      I haven't. I haven't.

    11. AH

      Are you close with anyone who, who has?

    12. TW

      I know people who have done it, yes, and I know people who, as a response, actually then supported the research that we have to, uh, been doing in this field. Um, there are companies now that offer this, what is called therapeutic plasma exchange, and there was a small trial that was, again, placebo-controlled in 40 individuals.... uh, from a company called Circulate Therapeutics, and they then looked in these individuals. These are healthy, older people, and they used some of these measures that allow us to assess how old an organ is, how old the body is, or how old an organ is, called epigenetic clocks. Um, and they could indeed see that some of the, uh, organs looked younger or the body overall looked younger. There's some improvements in function. Not dramatic, but suggesting that there might be something there.

  4. 12:50 – 15:28

    Sponsors: David & LMNT

    1. AH

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  5. 15:28 – 20:15

    'Young Blood' Factors, Rejuvenation, Stem Cells

    1. AH

      pack. I can imagine a situation where there are factors in blood that can damage tissues that arise when there's some sort of injury, let's say a heart attack or even a, a hip fracture, um, you know, pick, pick an injury. I can also imagine a situation where the blood of very healthy, vigorous, younger organisms is devoid of all of that. So when I'm thinking about what could be in young blood that could be rejuvenating, I can imagine that there's sort of a possible double dissociation there, that as we get older, we're having little... let's just call them micro injuries that we're not aware of all the time, and that infusing young blood into that person, um, would make them feel better. So you're counteracting the bad stuff. But there's another picture where you're supplying something that's pro-youthful. Do you know whether or not the proteins that are contained in young blood are inhibiting the damage-induced bad stuff, or it's supplying something that is really a kind of a youthful factor?

    2. TW

      Mm-hmm.

    3. AH

      Two different things.

    4. TW

      Yeah, yeah.

    5. AH

      Right?

    6. TW

      Yeah, yeah.

    7. AH

      And then, and you could see where they would interact, but the reason I'm getting granular here is because I think ultimately, for a therapeutic, you'd want to be able to, um, dissociate between these two.

    8. TW

      Yeah, yeah, yeah. No, it totally makes sense. And in a short answer, it's all of the above. [chuckles]

    9. AH

      Mm.

    10. TW

      Um, so what we see is with age, there's an increase in many what we call inflammatory proteins, and we actually identified some, and in mice, if we knock them out or if we neutralize them, then cognition improves-

    11. AH

      Mm

    12. TW

      ... in the mice, in old mice. So there you have examples of, uh, factors and actually natural factors that can inhibit some of these detrimental factors. But then you have also, um, active pro-growth factors, growth factors that, um, stimulate the activity of cells and might, you know, maintain stem cells better. So they're, they're truly beneficial factors, right? The challenge in this field has been to figure out which ones are the most important ones, and is there a, a smallest possible number of factors that you would need to have an effect, right? Sort of a cocktail.

    13. AH

      Mm-hmm.

    14. TW

      Now, you could say our blood is nature's cocktail, right? It's the, the elixir of youth. It just sort of... Or it's the fountain of youth that lives in us, but it dries out as we get older. But it also accumulates. There's also an accumulation of bad stuff, so it's not just a loss of that fountain. We have now tools where we can, in mice again, we can look at every cell in the body of a mouse, and we can ask, "How does the, do the cells in an old mouse respond to young blood?" And what you see is that almost every cell-... changes their behavior when we measure their transcript, so their gene expression in these cells, but they respond in different ways. And it's expected because they have different, what we call receptors, so one cell may respond to one factor and another cell to another one. And what's also interesting, we see a lot of stem cells seem to be targets of these young factors, which sort of proves what, what we originally described, but now in an unbiased way. We look at everything, and we ask, "What are the major effects?" And then you- what you also see that some organelles, such as mitochondria, these are the, the energy producer units in, in, inside cells, they are key targets of these rejuvenating effects. So it all makes sense based on what we know from the aging field, what we know from stem cells and maintenance of stem cells. But pinpointing which factor you would need to have this rejuvenating effect or which one you have to block has been extremely challenging, because you almost have to go into the organism, and then we call these CRISPR tools, where you can knock out one gene after another and ask which one is the important one. We can't really do this easily in vivo yet, but that's almost what we need to do. So unfortunately, in the past ten years, you know, there's individual factors that people keep describing, but I think we have not really come up with a good method to integrate multiple different factors that could provide more sort of an amplified benefit and mimic what, what nature is doing.

  6. 20:15 – 23:10

    Blood Banking; Dracula

    1. AH

      Should I be banking my blood?

    2. TW

      You don't have to, um, because what we find, even though there's differences, clear differences from one person to another, overall, if you have the blood of a young person, that blood has overall the s- a similar concentration from another young person, and it would still be beneficial to you. So all the blood that we ever used in our studies was always a pool from multiple individuals, and that still has the beneficial effect. So for, for these type of studies, you would not have to bank your own blood.

    3. AH

      Is the lore around Dracula based on this general logic? And if so, how do you think that lore arose? Meaning, I don't think somebody sat back and thought, "Oh, I can make up this story about this Count Dracula, who'd, you know, drank youthful blood," and-

    4. TW

      Yeah

    5. AH

      ... um, I mean, does that mean that experiments were being done long ago? I'm not trying to get gruesome here.

    6. TW

      Yeah, [chuckles]

    7. AH

      But we know, for instance, bloodletting and a bunch of other, um, you know, scientifically dubious, uh, uh, things have been used throughout history. But then again, to reduce iron load in the blood, some people will give blood. Um, it's also a nice thing to do for your blood bank. They need blood in hospitals, and too much iron load isn't good. We know that. So w- uh, what's known about the origins of the Dracula story, vis-a-vis the science that we are now aware of?

    8. TW

      Yeah, sort of in retrospect, I think where they came from is maybe more that people realized that, you know, blood is this essential fluid.

    9. AH

      Mm-hmm.

    10. TW

      If you get a cut-

    11. AH

      Mm-hmm

    12. TW

      ... and you bleed too much, you're dead, right?

    13. AH

      Mm-hmm.

    14. TW

      Um, but then maybe also associated it with, um, with age or youthfulness.

    15. AH

      Mm.

    16. TW

      I don't know exactly how.

    17. AH

      Yeah.

    18. TW

      We have not done, and, you know, [chuckles] this question came up many times before, we have actually never fed mice young blood. You could try that, right? To-- Because it would have to be absorbed.

    19. AH

      Mm-hmm.

    20. TW

      The factors would have to be absorbed into the body.

    21. AH

      Yeah.

    22. TW

      I wouldn't sur- be surprised if some of them wouldn't have beneficial effects and survive sort of the, the, you know, the, the, the, the stomach, um, acid environment of the stomach, but, uh, nobody's ever done it. I don't know where it comes from, but it's, [chuckles] yeah, I mean, there's a lot of these questions.

    23. AH

      Mm-hmm.

    24. TW

      And bloodletting, too, you know, it's blood thinning also, right?

    25. AH

      Mm-hmm.

    26. TW

      Uh, um, these leeches release factors into the blood, and they must have done something, otherwise people would probably not have done it.

    27. AH

      It's pretty wild. I, uh, again, not-- I'm not trying to be gruesome or medieval here. It's just, you know, now and again, something from, uh, the historical text shows up in, um, modern science, and-

    28. TW

      Yeah

    29. AH

      ... we kind of go, "Well, there's sort of a mapping of-

    30. TW

      Mm

  7. 23:10 – 33:02

    Rates of Aging in Organs, Age Gap & Disease Risk; Risk Profiles & Therapies

    1. AH

      drinking blood. I'm interested in organ-specific rates of aging. Um, and then I also want to circle back to organ-specific delivery of nutrients, because what you're talking about is blood infusion. It goes everywhere.

    2. TW

      Mm-hmm.

    3. AH

      It goes into the general circulation.

    4. TW

      Right. Yeah. Mm-hmm.

    5. AH

      You've mainly focused on the brain, but, um, it's possible that certain organs are more, uh, receptive to these youthful factors than others. I mean, even the brain has a blood-brain barrier. The gonads have a blood-

    6. TW

      Mm-hmm

    7. AH

      ... gonad barrier-

    8. TW

      Mm-hmm

    9. AH

      ... for interesting reasons. What is known about the rates of aging in different organs? Do they happen in parallel or no? And how different organs respond to these youthful factors?

    10. TW

      Yeah, so it's really interesting that, you know, intuitively, you think an organism just ages sort of as a whole, in synchrony, we would say, right? But what, uh, researchers have discovered, and this was first, I think Monica Driscoll, uh, was the first to show in worms, that when she looked with, at the ultra structural level, that some of these organs in the worm seem to look more aged than others. And over the years, now we have molecular tools where we can look at a single cell level or within an organ, and what we clearly see is that organs and cells within, uh, an organism can have slightly different rates of aging. And the way we conclude that is, if we look at all these tissues in many different organism, and we-... every, you know, period of weeks or months in mice, for example, we harvest tissues from different animals. We can see these trajectories, that some of them are relatively stable for a long time, and then they start to decline, where others continue decline from early adulthood. And, and yet others, you know, may maintain almost until the animal expires. So that allows you then, on an individual level, to ask if you compare now one individual to another, do their organs age exactly in the same way, or is maybe there a person, um, whose heart ages a little bit faster than their actual, the rest of their body, and in another person it would be the lung or the brain? And that's indeed what we seem to be seeing.

    11. AH

      Mm.

    12. TW

      And the way we did this in humans, and maybe we can talk about this now, is again, we look at these proteins, and there's company in- companies now that can look at thousands of proteins in a drop of blood. And this is not Theranos. This is, this is actually real, um, platforms, real science, where, uh, in, in just a drop of blood, there's companies that measure 11,000 proteins now, the concentration of these 11,000 proteins. And there's large population-based cohorts, uh, where people follow healthy people over two decades or even longer now, and they collected blood. And so we can profile this blood now, and we can ask, are proteins in that blood related to what diseases people develop or how they age? And the way how we make this, what people call a clock for a specific organ, is we look in your blood for proteins, for example, from the brain. So out of these thousands of proteins that we can measure in the blood, some of them originate from your brain. Some originate from the lung, from the liver, from the heart. And we've always used that in clinical medicine, but we measure only a handful of proteins, usually a few liver proteins, a few heart proteins, and we use them to assess injury or, um, uh, loss of function. So if your liver is damaged, that's what we detect. But here we have now an opportunity to look in thousands of people at proteins that come, for example, from the liver, and ask how do they change with age? And that allows us to then estimate the age of the liver in an individual. And what we find is that for most people, the age of your organs is pretty much in sync with your body. But for some individuals, you have more or less of a deviation. So your liver may a- age faster, um, than that of the rest of the population and the rest of your body. And what is really super exciting, we call this an age gap, so the difference between your actual age and the estimated age of your organ, and that's a very strong predictor of your future risk to develop disease in that organ.

    13. AH

      Mm.

    14. TW

      So in other words, if your heart shows to age faster, you're more likely to get heart disease or a heart attack. If your kidney ages fast, you're gonna get kidney disease. If your brain ages faster, you're more likely going to get Alzheimer's disease.

    15. AH

      Is this a test that anyone can now take? Is it commercially available?

    16. TW

      Yeah, so that's a great question. We started a company, uh, with, uh, Paul Koledha, um, called Vero Biosciences.

    17. AH

      Vero?

    18. TW

      Vero Biosciences.

    19. AH

      Mm-hmm.

    20. TW

      And the mission is really to profile the age of organs to ideally eradicate chronic diseases and to, um, maintain or to predict which organ is going to age. Because what we find is that if you have an organ that ages faster, if you can detect that and you can do an intervention, you can potentially delay aging, right, and extend health span. And this is really the mission of, uh, of Vero. The Vero Compass uses a combination of this biological signature together with clinical and wearable data to create a platform that can predict how you respond, which org- first of all, which organ is the most sensitive, which intervention you can use, and then whether your organ responds-

    21. AH

      Mm

    22. TW

      ... or not by repeated testing and sort of creating a continuous loop where I tell you which organ is of concern. You get medical advice based on other data that, uh, we can obtain from you, and then you may get an intervention. Could be a classic medical treatment, but it could also be a change in your lifestyle, exercise-

    23. AH

      Type of exercise

    24. TW

      ... change of diet, type of exercise-

    25. AH

      Mm

    26. TW

      ... but have it tailored-

    27. AH

      Mm-hmm

    28. TW

      ... to your specific needs, and then we can test, does that intervention actually change the age of your organ?

    29. AH

      It seems spectacular. I realize in addition, let's say I were gonna start a new medication, um, maybe, uh, taking a new drug for ADHD. Not for me, I don't have ADHD, fortunately, but you know, people are doing this all the time now, trying different drugs for different things-

    30. TW

      Right. Yeah

  8. 33:02 – 36:44

    NAD Levels & Aging, NMN Supplements

    1. AH

      I have a question that I promise I'm just gonna be... I, I, I've had this podcast long enough to know that I don't tap dance around things anymore. David Sinclair has been very, um-- I'm not a- trying to attack David, but I wanna know. David has been very vocal about NAD and the NMN pathway, which is, you know, upstream of at- of... And NR, others have talked about NR. There's, you know, Tru Niagen. I'm not trying to go after any one person or company, but for a while, there was a lot of excitement, mainly generated by David, that, um, NAD, which goes down across development into adulthood, uh, might be a pro-longevity treatment. I confess, I take NMN, um, powder. I don't get paid to say this. I know, I won't-- Doesn't even matter what company I get it from 'cause, uh, I buy it like everybody else. Um, I don't have any belief that it's going to increase my lifespan, but it seems to have a pro-energy effect that I like, and for some reason, it makes my hair grow very fast and my nails grow very thick, [chuckles] which is a side effect I wasn't looking for.

    2. TW

      Okay, maybe I should try it, too. [chuckles]

    3. AH

      Yeah. My sister experiences the same thing, but, you know, this is all anecdata, right?

    4. TW

      Yeah, yeah, yeah.

    5. AH

      Again, I make no money for saying this-

    6. TW

      Yeah, yeah

    7. AH

      ... but I've seen a lot of criticism of the NAD hypothesis of longevity, and so is there any evidence that increasing NAD levels, either through NMN or through NR or direct infusion or injection of NAD, any of those things, can actually extend the lifespan of humans and/or experimental models?

    8. TW

      Yeah, I mean, this is not my area of expertise, but, um, just as a blank statement, there is no human intervention that can extend lifespan that has been tested or validated. There are many that have shown beneficial effects in animal models, including NMN and, you know, all these metabolites. Um, there's actually a clinical study that shows that if you take these supplements, they increase your levels in the blood. That's a good clinical study, but it doesn't show that it has an effect on lifespan or even on frailty or any other tangible outcome. And this is the case with many other medications that might be beneficial-

    9. AH

      Mm-hmm

    10. TW

      ... but they have simply not been tested in a clinical trial. They have been tested in disease sometimes, and they are, you know, very good drugs to treat a person who is sick, but they have not test- been tested in healthy-

    11. AH

      Mm

    12. TW

      ... elder people and see whether they reduce aging or increase health span. There's really nothing out there except exercise and diets. Um, those have sort of proven, um, effects. There's a very good study from a researcher in, in, in Singapore who ac- tested ten different preparations of, of NMN, and she found that many of them actually don't contain what is on the label.

    13. AH

      That doesn't surprise me. Yeah.

    14. TW

      And that's the case for most supplements. For h- half the supplements, there's, you know, many resources out there you can check, or you can just ask ChatGPT.

    15. AH

      Sure. Mm-hmm.

    16. TW

      Um, there's not in there what it says, and with NMN, apparently, and according to ChatGPT, um, is very unstable, and so it, it degrades quite quickly. So you want to make sure, I think with any supplement, if you want to try it, make sure it's from a good source, um, and that it has been-

    17. AH

      Third party tested.

    18. TW

      That it has been-

    19. AH

      Yeah

    20. TW

      ... third party tested, yeah, and, and, and you use it within the, you know-

    21. AH

      Mm-hmm

    22. TW

      ... time frame.

    23. AH

      Yeah. No, I, I appreciate you saying that. I, um, like I said, I, I don't expect to live longer because of taking NAD. I just sort of like the effect that it-

    24. TW

      Mm-hmm

    25. AH

      ... appears to give

  9. 36:44 – 43:17

    Vitality vs Longevity; Periods of Accelerated Aging

    1. AH

      me.

    2. TW

      Yeah.

    3. AH

      I'd like to talk about the relationship between things that increase vitality, that are abundant in youth, versus their possible role in decreasing longevity. I've been fascinated by this for a long time, so, um, bear with me here, uh, and I'll try and set the stage, and then I'll be quiet.... puberty is perhaps the fastest rate of aging that we undergo in our entire lifespan. I mean, within two years, we transform as an organism.

    4. TW

      Yeah.

    5. AH

      Right? Some people progress through puberty much faster, other people seem to have a more protracted puberty. And here, I'm defining puberty as the acquisition of secondary sex characteristics. You know, facial hair, et cetera, uh, uh, reproductive, uh, ability, et cetera. Okay? So, um, puberty is a constellation of things that obviously differs in males and females. It's correlated with hormones like testosterone, estrogen, gonadotropins, et cetera, but really, it's a brain thing that switches on, that then start- initiates all of this. So there have been many attempts in the, the kind of health and wellness space to take the hormones, usually testosterone, estrogen, and growth hormone being the three primary ones, and then supply those to people in adulthood. Perimenopausal women taking estrogen and/or testosterone nowadays, quite frequent. It, this happens a lot. Uh, men, uh, taking testosterone, either because they need to, quote-unquote, "replace it," or they're just trying to augment what they already have. Growth hormone, certainly all of these things, dosed appropriately, we know will increase vitality, energy, libido, recovery from exercise, in some cases, maybe cognition, et cetera. But it's also been demonstrated that when you increase growth hormone in IGF-1, that you decrease lifespan.

    6. TW

      Mm-hmm.

    7. AH

      This is seen in large dogs versus small dogs. The reason larger dogs live so much shorter lives than small dogs is because of the dosing of IGF-1. So how do you look at the balance between vitality and longevity, and are there factors that can increase both vitality and longevity? Because to my knowledge, the things that, these hormones mainly, that increase vitality, well, if they allow you to exercise more and perhaps be leaner, then perhaps they buy you some time, additional time in life, but they also decrease the amount of time you have alive. So it's a very interesting interplay, and most people th- um, conflate longevity and vitality.

    8. TW

      That's an, an, an excellent question, and you know, short answer is we don't know. We don't really know, and in the aging field, this is called antagonistic pleiotropy. So something that is good when you're young can be bad when you're old, right?

    9. AH

      Mm-hmm.

    10. TW

      It, it relates to this, to this concept. And humans are, of course, you know, they're sort of exempt from evolution, uh, if you will, right? So our natural lifespan is probably around 30 to 40. If you look back in history, that's how long people lived.

    11. AH

      Really?

    12. TW

      I mean, there were always individuals who had, you know, exceptional lifespan, but most people would die much earlier.

    13. AH

      Of what?

    14. TW

      Infections, um, and ... It, it was probably mostly infectious diseases.

    15. AH

      Hmm.

    16. TW

      Um, but, you know, you could, you could argue from an evolutionary perspective, once you're sexually mature, you reproduced, and you guaranteed your offspring, which is around 30 to 40 years, nature doesn't care about you anymore, and so there's no longer... [chuckles] It's very brutal to hear, but-

    17. AH

      As long as your kids are, are sufficient enough to raise you.

    18. TW

      Exactly, yeah.

    19. AH

      I mean, an, an infant can't raise itself.

    20. TW

      Yeah. That's right.

    21. AH

      A seven-year-old maybe could-

    22. TW

      Yeah

    23. AH

      ... if they were very, uh-

    24. TW

      Yeah

    25. AH

      ... industrious.

    26. TW

      Yeah.

    27. AH

      You know?

    28. TW

      Yeah.

    29. AH

      But kids need us, at least until they're in their-

    30. TW

      They need us, yeah

  10. 43:17 – 45:22

    Sponsors: AG1 & Roka

    1. AH

      ... If you're a regular listener of the Huberman Lab podcast, you've no doubt heard me talk about the vitamin mineral probiotic drink, AG1. And if you've been on the fence about it, now's an awesome time to give it a try. For the next few weeks, AG1 is giving away a full supplement package with your first subscription to AG1. They're giving away a free bottle of vitamin D3 K2, a bottle of omega-3 fish oil capsules, and a sample pack of the new sleep formula, AGZ, which, by the way, is now the only sleep supplement I take. It's fantastic. My sleep on AGZ is out of this world good. AGZ is a drink, so it eliminates the need to take a lot of pills. It tastes great, and like I said, it has me sleeping incredibly well, waking up more refreshed than ever. I absolutely love it. Again, this is a limited time offer, so make sure to go to drinkag1.com/huberman to get started today. Today's episode is also brought to us by Roka. I'm excited to share that Roka and I recently teamed up to create a new pair of red lens glasses. These red lens glasses are meant to be worn in the evening after the sun goes down. They filter out short wavelength light that comes from screens and from LED lights, which are the most common indoor lighting nowadays. I want to emphasize, Roka red lens glasses are not traditional blue blockers. They do filter out blue light, but they filter out a lot more than just blue light. In fact, they filter out the full range of short wavelength light that suppresses the hormone melatonin. By the way, you want melatonin high in the evening and at night, makes it easy to fall and stay asleep. And those short wavelengths trigger increases in cortisol. Increases in cortisol are great in the early part of the day, but you do not want increases in cortisol in the evening and at night. These Roka red lens glasses ensure normal, healthy increases in melatonin, and that your cortisol levels stay low, which is, again, what you want in the evening and at night. In doing so, these Roka red lens glasses really help you calm down and improve your transition to sleep. If you'd like to try Roka, go to roka.com. That's R-O-K-A .com, and enter the code Huberman to save twenty percent off your first order. Again, that's roka.com, and enter the code Huberman at checkout.

  11. 45:22 – 51:25

    Sunlight; Youthful Blood Factors, Exercise & Brain Function, Fasting

    1. AH

      Lately, I've been, um, somewhat surprised, although not entirely, by some of the data on, um, sunlight exposure and lifespan. There's this really interesting large-scale study out of Sweden, where pe- the more sunlight exposure people got, the longer they live.

    2. TW

      Mm.

    3. AH

      Even smokers who get more sunlight-

    4. TW

      Mm-hmm

    5. AH

      ... appear to, on average, these are averages, folks-

    6. TW

      Yeah. Yeah, yeah

    7. AH

      ... seem to, so overlapping distributions-

    8. TW

      Uh-huh. It's interesting

    9. AH

      ... uh, live longer than, um, non-smokers who don't get sufficient sunlight. Now, getting a lot of sunlight is also correlated with outdoor activity-

    10. TW

      Mm-hmm

    11. AH

      ... fresh air, a number of things.

    12. TW

      Mm-hmm. Yeah, yeah.

    13. AH

      So it's, it's far from perfect-

    14. TW

      Yeah

    15. AH

      ... study, but, um, yeah, the interplay between vitality, and I think-

    16. TW

      Mm-hmm

    17. AH

      ... of sunlight as pro-vitality, um, and longevity is such an interesting one because the dance that we seem to be playing now with medications and, you know, could be supplements, but really medication and lifestyle, is what can we do and take to get more life, but also to enjoy that life more? And there are certain things like growth hormone, which will make people feel much more youthful-

    18. TW

      Mm-hmm

    19. AH

      ... much more youthful, skin, hair-

    20. TW

      Mm-hmm

    21. AH

      ... even cognition, et cetera. Ability to maintain or put on muscle, lose fat, and on and on. But higher IGF-1 and growth hormone, broadly speaking, means a shorter life.

    22. TW

      Yeah. Maybe comes at a price. Yeah.

    23. AH

      Yeah.

    24. TW

      Yeah.

    25. AH

      So I guess, um, I mean, that can be determined individually, whether or not somebody wants to make that trade-off. But what I'm excited about are the things that are possibly in these, uh, blood transfusions that come from younger humans, maybe us, but younger humans, you said pooled, um, that are getting to cellular function in a different way, that are restoring vitality and longevity. And maybe there are a few candidates that you could discuss with us, and what pathways they impinge on. I probably won't be familiar with the specific molecules, but are they impacting DNA, the, the epigenome? Are they impacting mitochondrial function? I- if you would maybe pick your two or three favorite candidates, if you, if you can. I know some of these are still under study.

    26. TW

      The factors often are growth factors. Um, GDF11 is, is one of them that has been described, growth and differentiation factor 11.

    27. AH

      Okay.

    28. TW

      There is... You know, IGF-1 actually also has been described to be in young blood is, is higher. There are factors that have been identified through an approach that is similar to transferring young versus old. So what one of my trainees, that Saul Villeda, when he was a graduate student in my lab, he did these parabiosis experiments. And then, uh, his lab and my lab independently, um, did an experiment where we exercised mice, young mice. We took their blood, and we injected it in non-exercise mice, and we could show that the beneficial effects of exercise on the brain were transmitted again by blood.

    29. AH

      Were you going young to young, so-

    30. TW

      We went young to young-

  12. 51:25 – 56:18

    Exercise, Injury & Inflammation

    1. AH

      this idea that was a- at least to me, first put forth in a book called Spark. Do you know John Ratey's book? It's some- it's, uh, you know, came out some years ago. He's a, a physician, I believe that trained at Harvard Med. Um, and he talked about the essential requirements for movement and brain plasticity. This was early days of understanding neuroplasticity, but, uh, he talked about brain-derived neurotrophic factor, other things that are liberated by, by exercise. But he describes some interesting experiments in there of, for instance, there's a, a, um, a sea-dwelling creature that swims around and has a fairly elaborate nervous system, at least for it, but then at some point in its life, settles down on a rock and eats its own nervous system, um, basically. [chuckles]

    2. TW

      Wow.

    3. AH

      And there's been some interesting experiments looking at what happens when you get, uh, that organism or other organisms, I believe, I think it was that organism, but other organisms to continue moving. It seems like there's feedback from the process of moving the musculature, and then it could be neur- neuromuscular in origin, it could be hormonal in origin. I, I, I don't think we know that it comes from muscle, but there's something about the requirement for movement that signals to the brain that it needs to continue to exist, and not just the motor portions of the brain, and that it... or the portions of the brain controlling motor activity, but that the body may supply chemical or other types of feedback to the brain that if, if it's moving and continues to move, that the brain needs to continue to be robust.

    4. TW

      Mm-hmm.

    5. AH

      Which I find very interesting-

    6. TW

      Yeah

    7. AH

      ... because few things, to me, explain how movement to the body would signal vitality of the brain, aside from hormone-

    8. TW

      Mm-hmm

    9. AH

      ... borne factors. But it kinda makes sense.

    10. TW

      Yeah.

    11. AH

      Right? Continuing to move the body-

    12. TW

      Hmm. Yeah

    13. AH

      ... is essential for keeping the brain healthy.

    14. TW

      Yeah. Yeah. Yeah, and, I mean, exercise interventions, you know, there's thousands of studies that show that exercise is beneficial, cardiovascular, but also other exercise.

    15. AH

      Yeah, now it seems everyone's excited about resistance training. I, I mean, I think both is, is clearly the answer.

    16. TW

      Yeah.

    17. AH

      I mean, you're, you look good. What, what's, uh... I mean, you're, you're not in your 80s, but, [chuckles] um, do, do-

    18. TW

      I might be. [chuckles]

    19. AH

      Do you exercise? Right, right. Yeah, that would be impressive.

    20. TW

      [chuckles]

    21. AH

      Um, what, what is your exercise regimen? People will wanna know.

    22. TW

      Yeah.

    23. AH

      Yeah.

    24. TW

      I, I, I run.

    25. AH

      Mm-hmm.

    26. TW

      Uh, I like running outdoors.

    27. AH

      Mm.

    28. TW

      I like the sun. [chuckles]

    29. AH

      Mm-hmm.

    30. TW

      Um, I, I try to get two runs, five to 10K.

  13. 56:18 – 1:02:35

    Pro-health Factors, Klotho, GDF11, Stem Cell Injection Risk

    1. TW

      Yeah.

    2. AH

      So how do we move past correlation and to really understand, um, causative stuff? So we'll get back to lifestyle factors, but, I mean, it's so very clear from the animal studies and from the human studies that you described, that there's something in young blood or things in young blood-

    3. TW

      Mm-hmm

    4. AH

      ... that are pro-rejuvenation for the brain and other tissues. How do we get to a, a real pro-longevity molecule medication treatment?

    5. TW

      Or pro-health, maybe more, right? I think most people in the field are not really interested in ex- extending lifespan, which would be longevity, but healthspan.

    6. AH

      Mm-hmm.

    7. TW

      So, and we talked about this before, right? That you try to maintain the function of your organs until you die, so that your brain would still be functioning, you're cognitively intact, all your organs would still be functioned relatively well, and then, you know, you fall asleep, and, and that's the end of your life. Um, and not necessarily extending lifespan. As you said, it could be that we extend lifespan, and you just have 10 more miserable years. That, certainly, nobody would want that, right?

    8. AH

      Mm-hmm.

    9. TW

      But I think to get to causation, we need these types of experiments, physiological experiments in animal models first, to isolate individual factors and then test them on an individual basis with very rigorous methods, so which we can do, and say: Okay, this factor has the capacity to maintain, for example, brain function in the mouse. And then we have to test it in humans and do it in a, in a careful, clinically, uh, controlled trial, where people are blinded, whether they got the treatment or not, and do a big enough study that we can say, "Okay, this truly works," and then we have a drug.

    10. AH

      How close are we to the clinical trial?

    11. TW

      There are different molecules. Klotho is actually another one. It's this, um, protein that, uh, has been described to have beneficial effects on multiple different organs. The biology, again, not exactly clear, but-

    12. AH

      K-A-L-O-T-H-O, Klotho?

    13. TW

      That's right. Yeah, yeah.

    14. AH

      Mm-hmm.

    15. TW

      Um, and, you know, there's, there's companies trying to move this into humans, into human trials. Um, some of these other factors, I think there, there are companies are trying, uh, or inhibiting detrimental factors. And with, with, you know, individual clinical trials, you could get there, um, in the next five, 10 years. There may be something that has an effect. I think we will not have a factor, an individual factor, that just has, you know, this miracle effect on everything. This is very clear from the studies of young blood. It's many different factors, and they target different pathways, different cell types in different tissues. So you really need to- you may have to decide, you know, for this organ, we need this treatment, for this organ, we need that treatment, to optimize its function and keep it, you know, running at full capacity until you're 100 years old.

    16. AH

      I'm not suggesting anyone do this, but I, I do seem to hear now and again that people are taking Klotho already. Um, not surprising.

    17. TW

      Yeah.

    18. AH

      People will-

    19. TW

      Yeah

    20. AH

      ... you know-

    21. TW

      Yeah

    22. AH

      ... get ahead of the curve-

    23. TW

      Mm-hmm

    24. AH

      ... so to speak.

    25. TW

      Yeah.

    26. AH

      Um-

    27. TW

      I also read people taking this GDF11. Um, I don't know where they get it.

    28. AH

      I'm guessing it's just, uh, Mexico and, um, Central and South America, there's, there are a lot of clinics that do this sort of thing. I, I will put out a, a true story, um, cautionary note. Uh, a friend who, uh, when pe- whenever people say, "I have a friend"-

    29. TW

      Mm-hmm

    30. AH

      ... and so, you know, but this is a medical doctor, um, who had a back pain that was, uh, giving him a lot of issues, and he went to a stem cell clinic in Mexico, got an injection of stem cells into a spinal disk, which my neurosurgeon friends tell me is a terrible idea. It turns out the disk cannot accept cellular injections. A neurosur- a ch- a chair of neurosurgery-

  14. 1:02:35 – 1:05:43

    Platelet-Rich Plasma (PRP); Exosomes

    1. TW

      trust.

    2. AH

      Thank you. Uh, by way of contrast, um, platelet-rich plasma, PRP-

    3. TW

      Mm-hmm

    4. AH

      ... is approved by the FDA.

    5. TW

      Yeah.

    6. AH

      People who are undergoing fertility treatments will get it injected into their ovary. People are getting PRP injected into their shoulders, their knees, their whatever. Uh, I'm not trying to be disparaging of this. It is FDA-approved. To my knowledge, platelet-rich plasma does not contain stem cells.

    7. TW

      That's correct.

    8. AH

      But it seems to be beneficial enough and safe enough that the FDA has approved it. Uh, what is the deal with platelet-rich plasma? What has it been shown to be actually useful for? Because just because something is allowed for one indication and is used broadly for a bunch of things, doesn't mean that there's evidence that it works for all those things.

    9. TW

      That's right.

    10. AH

      Yeah.

    11. TW

      That's right. Uh, so platelet-rich plasma has these platelets in there that are full of growth factors. They have these granules that help in wound healing, as a primary function, and, um, somehow that seems to be beneficial. In sports injuries, it's often given.

    12. AH

      Mm-hmm.

    13. TW

      And as far as I know, I think it's from your own blood.

    14. AH

      Yeah.

    15. TW

      You, you, you concentrate these plat- platelets, and then they release these factors. So you may have a massive load of growth factors that help you heal these various tissues that you mentioned. Yeah.

    16. AH

      Yeah. I haven't tried it, but I know people who have and, and reported some positive effect. I've heard also a lot about exosomes, and there are some clinics, I believe, where, uh, I think exosomes are FDA-approved as a treatment. What are exosomes, and what, what have they been shown to be useful f- for in studies and/or clinical?

    17. TW

      I don't know in clinical studies how they're used, but, um... So cells can release sort of little packages of material that is filled with proteins, but there's also RNA molecules in there, lipids, metabolites. And some cells do this all the time. Cancer cells, for example, do it, but also some immune cells ha- have a very active release of these little, f- um, sort of like little packages, vesicles we call them, that are filled with, um, again, all these different molecules. In the blood, you find large numbers of these exosomes, and that's where they're usually purified from. Different cells have different cargo in these, in these vesicles, and it seems that they function to some extent to deliver information from one cell to another. It's still a very new field, but people explore, you know, whether they can be used for, for treatment purposes, but also for diagnostic purposes. Do they tell you something about a specific organ or a tumor that is developing? So when we measure these proteins that we talked about earlier in the blood, um, we actually measure what's in the exosomes also. So these exosomes, they float basically, like immune cells, they float in the blood, and, uh, we open them up, and we measure what's inside.

  15. 1:05:43 – 1:11:28

    Smoking, EMFs, Plastics, Long-Term Accumulation, Fresh Foods, Organic Food

    1. AH

      We should probably talk about some of the things that damage vitality and longevity. Accident and injury aside, we know that smoking, especially nicotine, um, damages DNA, uh, increases inflammation, and will shorten your life. I don't think there's any debate about that.

    2. TW

      Yeah.

    3. AH

      Right? But what about some of the other things that might produce low-level DNA damage? In particular, these days, I'm very interested in EMFs. Uh, I don't actually believe that the low levels of EMFs that are present in most technologies are damaging in the acute, uh, way, that, you know, being near them is gonna harm you, but there is the idea that things can be cumulative, right? I mean, I get one X-ray every few years when I go to the dentist, but there's a reason the clini- the, the technician runs behind, uh-

    4. TW

      Yeah

    5. AH

      ... the wall. Uh, he or she doesn't wanna be exposed to that on a daily basis. So how do we feel about things that at a low dose don't damage DNA, um, or mutate proteins either, but that if we are exposed to them over a lot of time, could very well do that? Um, what are your thoughts on this?

    6. TW

      A very difficult question. I mean, you could ask the same question about any chemical that we invent and we put into food or we get exposed to, right?

    7. AH

      Mm-hmm.

    8. TW

      The, you know, the plastic. We, you know, we drink out of cups, hot stuff out of a cup that is-

    9. AH

      Mm

    10. TW

      ... coated with plastic and, you know, or full of plastic. How is that gonna change our lifespan? It hasn't in a, in a measurable way so far, right? But we don't know what's gonna happen in 20, 30 years-

    11. AH

      Right

    12. TW

      ... or if people, you know, synthesize a compound that is detrimental, that it doesn't look detrimental, it has been tested and is safe, but as you said, if, if it accumulates maybe, or in combination with other stuff, it may be detrimental.

    13. AH

      I think about this from time to time, and, and I wonder about what's in my environment that I can easily control. I try not to drink out of plastic. Um, I-... uh, you know, I try and drink out of cans that don't have BPAs and things like that, if I can.

    14. TW

      Yeah, if you, if you go down that route, you know, it drives you crazy, and you could, you know, sort of not do anything [chuckles] anymore or not eat anything.

    15. AH

      Well, it's getting-

    16. TW

      I mean-

    17. AH

      - harder nowadays-

    18. TW

      It gets hard

    19. AH

      ... to live, to live a clean life. I mean, how long were you in Switzerland before you came to the States?

    20. TW

      I was twenty-six.

    21. AH

      Mm-hmm.

    22. TW

      Yeah.

    23. AH

      You were weaned in a very clean environment. Very, you know, uh, that's not just a, a, uh, stereotype about-

    24. TW

      Yeah

    25. AH

      ... about the Swiss, meaning things are, yes, very tidy and clean.

    26. TW

      Right.

    27. AH

      The streets are-

    28. TW

      Yeah

    29. AH

      ... remarkably clean.

    30. TW

      Mm-hmm.

  16. 1:11:28 – 1:13:16

    Sponsor: Function

    1. AH

      I'd like to take a quick break and acknowledge one of our sponsors, Function. Last year, I became a Function member after searching for the most comprehensive approach to lab testing. Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health. This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more. They've also recently added tests for toxins, such as BPA exposure from harmful plastics, and tests for PFAS, or forever chemicals. Function not only provides testing of over 100 biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas. For example, in one of my first tests with Function, I learned that I had elevated levels of mercury in my blood. Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption, I'd been eating a lot of tuna, while also making an effort to eat more leafy greens and supplementing with NAC, N-acetylcysteine, both of which can support glutathione production and detoxification. And I should say, by taking a second Function test, that approach worked. Comprehensive blood testing is vitally important. There are so many things related to your mental and physical health that can only be detected in a blood test. The problem is, blood testing has always been very expensive and complicated. In contrast, I've been super impressed by Function's simplicity and at the level of cost. It is very affordable. As a consequence, I decided to join their scientific advisory board, and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, you can go to functionhealth.com/huberman. Function currently has a waitlist of over 250,000 people, but they're offering early access to Huberman Podcast listeners. Again, that's functionhealth.com/huberman to get early access to Function.

  17. 1:13:16 – 1:19:07

    Intermittent Fasting, Long-Term Fasting, Snacking

    1. AH

      Well, as long as we're talking about food, we should talk about not eating. We should talk about fasting. So many studies now showing in worms, in mice, in monkeys, and perhaps even in humans, that subcaloric intake or intermit- uh, for long periods of time, or perhaps intermittent fasting, we can talk about how we define that, um, can extend life. How is that thought to work? Is it the reduction in this mTOR, mammalian target of rapamycin? Is it, um, reduction in inflammation? Is it clearing of senescent cells? G- give us the, the overview and, a- and any specifics about intermittent fasting and, and-... perhaps start by saying how you define intermittent fasting. Is it daily or is it two, three days?

    2. TW

      I think to, to just answer that-

    3. AH

      Yeah

    4. TW

      ... there is no definition. [chuckles]

    5. AH

      Okay.

    6. TW

      There is no definition.

    7. AH

      Mm-hmm.

    8. TW

      And the whole field is also a mess. Um, you know, it's again, taking studies in mice, for example, um, and then translating them to humans. You know, the, their lifespan, the, their whole rhythm, um, their environment is so different from our environment, right? That to translate these, um, is, is always a stretch. And there's no clinical studies that show a clear benefit of, of fasting in humans. And some studies in monkeys actually suggest that it's detrimental, um, for monkeys to fast, for example. They had more, um, uh, I think worse kidney function and things like that. Um, so overall, in, from animal studies, it's very clear that you activate sort of beneficial pathways. They're very diverse. Um, again, we can now use unbiased, um, assessment of many different cell types in an organism at, you know, gene expression across thousands of genes, and we see that different cells respond in different ways, and you get functional improvements. But they're very broad. They're, in part, reduced inflammation. Um, other cells, um, you get benefits on their energy metabolism, protein turnover, how they handle sort of what we call the garbage that accumulates in cells. Um, overall, from these animal studies, clearly benefits from reducing calorie intake. Uh, also less what we call oxidative damage, so it's like you, you burn a fire, right? Then e- if, if that fire is really intense, you may cause more damage. But how you translate this really to tangible benefits in humans, I'm not sure.

    9. AH

      Do you practice intermittent fasting?

    10. TW

      Rarely.

    11. AH

      You like breakfast?

    12. TW

      I, I tried, um, you know, Longo's, uh, diet, uh, a few times, where I reduce, uh, you, you, you reduce calorie... Valter Longo, do you-

    13. AH

      I, I'm familiar with him.

    14. TW

      Yeah.

    15. AH

      What's, what's the t- the contour of the diet?

    16. TW

      Yeah. So it's mostly you switch to a ketogenic diet, so a fat-rich diet, so your metabolism changes basically from a, a regular sort of glucose-driven diet to burning fat. Um, and you feel that when you start to starve, that somehow it's almost like your body changes a little bit, and, um, you, you get a bit more alert almost. And in a way, that makes sense, right?

    17. AH

      Mm-hmm.

    18. TW

      If you think you're out there in a wild, in the wild, whether you're an animal or a human being, if you don't have enough food, the last thing you want is that your brain doesn't work well.

    19. AH

      Right.

    20. TW

      Um-

    21. AH

      I imagine the catecholamines, dopamine-

    22. TW

      Yeah

    23. AH

      ... norepinephrine and epinephrine increase.

    24. TW

      Yeah, mm-hmm. Yeah.

    25. AH

      Yeah.

    26. TW

      So you get more alert, right?

    27. AH

      You're a little hangry.

    28. TW

      Yeah, [chuckles] hangry, exactly. [chuckles]

    29. AH

      Got it.

    30. TW

      Um, but, um, I'm not sure how long that lasts and how beneficial this is in the long run.

  18. 1:19:07 – 1:24:44

    Sleep; Cerebrospinal Fluid (CSF) Factors & Cognitive Function

    1. AH

      And that's what I'd like to discuss also is sleep. If there's been at least one i- there's probably been three in my mind, but at least one major triumph in the public health discussion over the last, let's say, 10 years, it's... And we can really, truly thank the great Matt Walker for this, um, who wrote Why We Sleep. You know, he was the first person to really say, "Hey, these are all the terrible things that are gonna happen to you if you don't sleep enough."

    2. TW

      Mm.

    3. AH

      And everyone needs different amounts. I'm fine on six hours, so I don't believe everyone needs eight.

    4. TW

      Mm.

    5. AH

      I, I, seven, I'm great, but I'm fine on six w- especially with a little nap here and there. But Matt got people scared, then he got people thinking about how to improve their sleep, and m- I and others have spent time on this. I think that's one of the great victories of, of public health communication around, um,... the s- the best science. Uh, the other would be the importance of exercise, um, both cardiovascular and resistance training. But during sleep, we know that there's this so-called glymphatic clearance, the, the clearance of junk from, uh, all the tissues, but in particular from the brain, uh, that's facilitated by the glia, hence glymphatic. Um, have you guys looked at lymph between young and old animals? I'm fascinated by lymph.

    6. TW

      I have not. Yeah, that would be very interesting to do. We thought about it, but this-

    7. AH

      Because it's the debris from the blood, right?

    8. TW

      Yeah.

    9. AH

      It's the d- well, it's the-

    10. TW

      Yeah

    11. AH

      ... debris from the extracellular space-

    12. TW

      Yeah, yeah

    13. AH

      ... that doesn't get picked up by the blood.

    14. TW

      Mm-hmm. Yeah.

    15. AH

      I mean, it's essentially the, the extra bad stuff, all the-

    16. TW

      Mm-hmm. Yeah

    17. AH

      ... ammonia and-

    18. TW

      Yeah

    19. AH

      ... cellular debris and fragments.

    20. TW

      Mm-hmm. Yeah.

    21. AH

      I would love for you guys to do an experiment looking at lymph-

    22. TW

      Yeah

    23. AH

      ... from young and old-

    24. TW

      Yeah, yeah

    25. AH

      ... animals.

    26. TW

      I mean, we looked at the cerebrospinal fluid, but it's of course different. And that, again, differs dramatically with age. The composition changes dramatically. And I had a fellow who was heroic enough or [chuckles] crazy enough to collect, um, young CSF from, from animals, from mice.

    27. AH

      Tiny, tiny little?

    28. TW

      Yeah.

    29. AH

      Wow!

    30. TW

      And then infuse it, uh, via a pump, um, over a month into old animals. And she could show that you can regenerate the brain, um, improve cognitive function in these mice. And, um, oligodendrocytes, these cells that wrap the connections between neurons, it's like the- they produce the, the, the plastic around the wire, right, if you will, they were the, the, the strongest target if we looked in an unbiased way. Uh, and so she's studying that now in her own lab. But it shows you, in another way, how a fluid changes from young to old, and the young fluid somehow, um, has beneficial factors that benefit, uh, the old brain. And so I wouldn't be surprised that, um, there could be beneficial factor in the glymph or the, the lymphatics-

  19. 1:24:44 – 1:32:02

    Exercise Type & Longevity; Exercise Enjoyment

    1. AH

      It's always tough to get to causality, but, uh, anytime I see a study that looks at, in a correlative way, at, you know, like, which athletes live the longest-

    2. TW

      Mm-hmm

    3. AH

      ... it's very interesting, right?

    4. TW

      Yeah.

    5. AH

      I mean, I have no desire to run a marathon.

    6. TW

      Mm-hmm. Yeah.

    7. AH

      Um, but if I knew that it was gonna add 20 years to my life or 15 years, I might start-

    8. TW

      Mm-hmm

    9. AH

      ... becoming a marathoner. But a recent study showed that, um, it's the pole vaulters, I'm not gonna get into that, [chuckles] and the gymnasts, and I think the high jumpers and the sprinters, so the fast-twitch muscle folks, that i- they get a substantial longevity effect-

    10. TW

      Mm-hmm

    11. AH

      ... you know, five to eight years-

    12. TW

      Yeah

    13. AH

      ... on average-

    14. TW

      Yeah

    15. AH

      ... more than their, you know, age match cohorts.

    16. TW

      Oh, that's really interesting. Yeah

    17. AH

      Even compared to other-

    18. TW

      Yeah, yeah

    19. AH

      ... uh, high- highly trained athletes.

    20. TW

      Mm-hmm. Yeah.

    21. AH

      So I see a result like that, and then, of course, the, the reduction of scientist in me-

    22. TW

      Mm-hmm

    23. AH

      ... says, "Okay, so is it the running? Is it the jumping? Is it..." But then you think, like, "Oh, using the Wyss-Coray model, I mean, you could essentially look at the blood from-

    24. TW

      Mm-hmm

    25. AH

      ... sprinters versus-

    26. TW

      Yeah

    27. AH

      ... marathoners.

    28. TW

      Fair, yeah.

    29. AH

      And of course, they're going to differ.

    30. TW

      Mm-hmm.

  20. 1:32:02 – 1:37:05

    Lifestyle Factors & Alzheimer's Risk; Cognitive Exercise; Chocolate

    1. TW

      and, you know, it's interesting that you say that. Um, Jill Livingston and others, um, you know, they, they have studied, um, sort of how lifestyle influences the development of dementia and Alzheimer's disease, and it's a dramatic component that you can influence, um, easier or not, right? I mean, some of them are very hard to get out of, but, you know, poverty, uh, is a risk, of course, um, childhood obesity, uh, lower education, um, smoking, excessive alcohol use. Um, many of these things that we know, you know, they're good or bad. If you have all these-- I- if you optimize everything, your risk for dementia is much lower. I mean, there's now, you know, countless studies that, that show that. So there, there are things that you can do, the lifestyle factors, right? Um, and they're easier to do for some people than for others. But it's clear that, um, there's incredible power in, um, lifestyle and, and what we do.

    2. AH

      Are you aware of any correlates to the exercise thing we were just talking about, whereby certain, um, cognitive exercises can, uh, help us hold on to cognition? For instance, we've heard doing crossword puzzles or, you know, reading good books. I mean, the-- I think this is becoming increasingly important because it's so easy to have one's time sucked away on the internet or on social media, um, nowadays, which requires essentially no work, right? You just scroll and read. I mean, I mean, articles have become very brief. Is there any known benefit of trying to tackle cognitive, uh, gymnastics? Is there any data?

    3. TW

      Not to my knowledge. Unfortunately, you know, the, the studies that looked, um, in patients who already have cognitive impairment and, um, you try to give them sort of, uh, exercise and mental exercise, they don't do much-

    4. AH

      Mm-hmm

    5. TW

      ... unfortunately. It's probably more complex. And you, of course, also have, again, you know, what we discussed earlier with exercise, right? Some people just love to be stimulated and, you know, they want to learn something new, you know, want to learn a new language or a new instrument, and their mind is already attuned to that, right? They, they crave for this. And for others, um, that might be much harder, and, and, and, and they may not benefit from it. Um, but you're the neuroscientist. You know, w-what, what... I mean, [chuckles] you know, what, what could you get out of, of something like that? And if, if somebody is, is really, um, excited about, you know, doing any of these mental exercises versus, you know, it doesn't speak to them.

    6. AH

      Mm-hmm. Yeah, I think that w- if w- we should all find the things that we want to do enough that we would elect to do them, but that are challenging. There are data coming out now showing that handwriting is very important to development of certain brain circuits.

    7. TW

      Mm.

    8. AH

      It's kind of a no surprise, but this is important for the younger generation who's no longer handwriting so much. The phrase, "Use it or lose it," makes perfect sense to me. I mean, if you don't walk enough or run enough or cycle enough or do anything with your legs, eventually, the, the neural systems that control your legs will atrophy, as will the muscles. We tend to think about the muscles-

    9. TW

      Yeah

    10. AH

      ... but we don't think about the neural control over the muscles. So I think as, since I'm fifty now, I think, you know, I make it a point to read at least, it's gonna sound so paltry, but at least one page, and ideally one chapter of a book every day. Sometimes it's just one page, but just with a book, with my phone out of the [chuckles] room. And I do, and I read papers and things like that, but doing things that feel unnatural, um, but that I know I will benefit from when they're over. There's s- such a deep feeling of satisfaction from having done that sort of thing.

    11. TW

      Right.

    12. AH

      And for me, the, the higher intensity cardio is that. I'd ra- I'd much rather jog than sprint, so I make it a point to sprint, you know? So I think maybe we should think about exercise and cognitive stuff the same way.

    13. TW

      Who knows?

    14. AH

      Yeah. I mean, w- is there anything in, in Switzerland that they do that they don't do here in terms of food and exercise and lifestyle? Because the Swiss are very healthy. The Swiss also, as I recall from something in The Economist a few years ago, when I used to... I no longer subscribe to them, but the highest caffeine intake in the world is the Swiss.

    15. TW

      Really? [chuckles]

    16. AH

      They drink so much caffeine.

    17. TW

      Also chocolate. [chuckles]

    18. AH

      Yeah. Yeah, good chocolate.

    19. TW

      Chocolate and cheese.

    20. AH

      Oh, yeah.

    21. TW

      Um, and people eat a lot of it. I eat almost every day, I eat chocolate.

    22. AH

      Do you?

    23. TW

      Yeah, yeah.

    24. AH

      You're making some people very happy.

    25. TW

      It's... Yeah.

    26. AH

      I eat 100% chocolate.

    27. TW

      It's part of my diet.

    28. AH

      When? When do you eat it?

    29. TW

      Usually after, you know, with a coffee after lunch or so.

    30. AH

      High in polyphenols.

  21. 1:37:05 – 1:40:50

    Alcohol & Social Connection; US vs European Food Culture

    1. AH

      own a winery.

    2. TW

      That's right. Rejuvenate. [laughing]

    3. AH

      That runs counter to everything I understand about longevity, but it runs-

    4. TW

      No, it doesn't!

    5. AH

      Very m- Okay, all right, here we go.

    6. TW

      Yeah.

    7. AH

      Educate me.

    8. TW

      Alcohol itself is probably not good for our body, right?

    9. AH

      Right.

    10. TW

      Just pure alcohol.

    11. AH

      Right.

    12. TW

      But a lot of drinks are part of a social environment, and, and I think one of the major benefits that people have attributed to, you know, wine, um, is the social aspects of it.

    13. AH

      Mm-hmm.

    14. TW

      I mean, some people may drink a bottle of wine by themselves, but I think the majority, you know, they have a meal together, and you share a bottle of wine. And that's... We talked about this earlier, you know, how you dissociate one thing from another.

    15. AH

      Mm-hmm.

    16. TW

      I think, um, you know, there's this complexity that you, you see actually in almost all studies that look at centenarians, you know, where people lived the longest. Um, one of the most-... common aspect is that they're all very social. They're not left alone when they're old. They have a community, and they, they meet other people, right? And so I think that's part of the, the wine culture, is really, um, being social, being together.

    17. AH

      Mm-hmm.

    18. TW

      Yeah.

    19. AH

      Yeah, I mean, the data on social connection and stress reduction, huge. Yeah, I've gone on record saying that the data say zero alcohol better than any. Two drinks per week is probably the upper limit for a non-alcoholic adult, um, after which I just say, "You know, make sure you're doing other things correctly." One thing that I w- I, I wanna be really, um, clear on is, since I'm talking to, um, someone from, originally from Switzerland, although you're a US citizen now, um, is that the United States has never had a history of healthy food or drinking habits. You know, if you think about classic American cuisine, it's all unhealthy stuff: apple pie, french fries, hamburgers, hot dogs, pizza, which was n- originally not ours, right? And, and on and on, right? There, there's been a, a culture of volume and abundance, um, and kind of amusement park food-

    20. TW

      Mm-hmm

    21. AH

      ... frankly. And the same is true for drinking. I mean, uh, certainly not speaking for everybody, but there's been a culture around alcohol in the United States of drinking a lot of beer or a lot of spirits. Whereas I think in Europe, um, the food, including the desserts, have a, have a tradition of nourishment, of social connection. And sure, we have bars in the United States, and people drink beer while they watch games and things like that, but I think sometimes that gets lost in the conversation, um, that the United States has never been a particularly healthy place, except be- for its level of, of engagement in sports and exercise until recently. So I, I totally agree with what you're saying. If you're getting together with friends and-

    22. TW

      Mm

    23. AH

      ... having a couple drinks or something like that, that, that sounds entirely healthy. But, um, the problem is that's usually not how it looks on, uh-

    24. TW

      Yeah

    25. AH

      ... certainly not on college campuses, but that's a- another thing.

    26. TW

      Well, excess is, right?

    27. AH

      Yeah.

    28. TW

      Anything, if you... Also with food, if, I mean, I eat any food. You can eat any food, but you don't want to just eat one food. I mean, I eat french fries as a-

    29. AH

      Mm

    30. TW

      ... or a burger. There's nothing wrong with it-

  22. 1:40:50 – 1:49:13

    Deliberate Deep Breathing; Wearables, Sunlight & Artificial Light

    1. AH

      I'm gonna get a little, uh, wacky here, not woo wacky. [chuckles] There's some really interesting stories about improving health and vitality, maybe lifespan, with things that adjust blood flow. So for instance, in the literature around qigong breathing, right? Uh, and there's a lot of different forms of this, but we, we can, we can distill things down to the fact that inhales, vigorous inhales, increase the heart rate.

    2. TW

      Mm-hmm.

    3. AH

      Um, exhales, deliberate exhales, extended exhales, decrease the heart rate-

    4. TW

      Mm

    5. AH

      ... through something called respiratory sinus arrhythmia. So in a number of cultures, they'll do, um, qigong, tai chi, which is deliberate breathing and movement, of course.

    6. TW

      Yeah.

    7. AH

      And the idea is that you're improving circulation, that it feeds the brain, you know, in the language of these things, that it's feeding the brain nutrients, and it all makes perfect sense, given, given what you're saying. It's also interesting... I, I've been looking at, um, how patterns of breathing change as people age and talking to people who work in hospitals and with- And there's some, actually a little bit of data around this. As people get older and their cognitive function goes, they tend to become mouth breathers. [panting]

    8. TW

      That's interesting.

    9. AH

      They're, they're having trouble-

    10. TW

      Mm-hmm

    11. AH

      ... oxygenating their brain.

    12. TW

      Mm-hmm.

    13. AH

      Now, it could be the mouth breathing is the cause, or it could be reflective of-

    14. TW

      Yeah, yeah

    15. AH

      ... of something else. Kind of interesting to think about because the relationship between breathing and blood flow is a, is a, is an obvious and well-established one. So there are all these things about the young blood versus old blood that might be independent of pure biochemistry of aging-

    16. TW

      Mm-hmm

    17. AH

      ... that could be controlled with-

    18. TW

      Mm-hmm

    19. AH

      ... lifestyle factors.

    20. TW

      Right.

    21. AH

      And we say exercise improves, uh, health span-

    22. TW

      Mm-hmm

    23. AH

      ... but exercise increases breathing rate. So have you, um, uh... Are you at all interested in... I'm trying to get a bunch of studies going here, you can tell. In people that do some sort of deliberate deep breathing, it doesn't have to be tai chi-

    24. TW

      Would be super interesting.

    25. AH

      Right?

    26. TW

      Yeah.

    27. AH

      Because you're changing the chemistry of the blood.

    28. TW

      I mean, anything, you know, what we discussed earlier is this cause and effect, and the, the really, the way to show that something has an effect is you have a study where some people, you take their blood, they do an exercise, and then you take their blood again, and you look, does it change something?

    29. AH

      Mm.

    30. TW

      Very easy to do. But-

  23. 1:49:13 – 1:56:40

    Future Projects

    1. AH

      Tell me, is there anything that you're particularly excited about that I did not ask you about? What... Uh, you've been publishing so well for so long now, and you really put this whole field of looking at blood-borne and other, um, factors correlated with youth, um, as a therapeutic, you really put that on the map in a serious way. And I, I really wanna congratulate you for doing that on a backdrop of, uh, Dracula stories and kind of sensationalism around that. You're, you're clearly a serious scientist, taking things on seriously, and also measuring mult- multiple factors from blood, as you know, has a kind of a complicated history, but you, you've really moved this forward in a, in a, um, in a very rigorous way, and so-

    2. TW

      Yeah

    3. AH

      ... that's awesome. What are you-... thinking about these days-

    4. TW

      Yeah

    5. AH

      - that I wouldn't know about?

    6. TW

      Yeah, thanks for the opportunity. Yeah, so one thing that, um, should later this week actually be, um, publicly available on, on a preprint server. So we took this idea of looking at, um, organs and, you know, getting an estimate of how old is your brain or your heart. We took this to the next level and asked: Can we build similar models and estimate how old cells are in your body? So we have many different cell types, right? That's how we have specialized organs. So we were able to, with the current technology that measures these thousands of proteins, we were able to assign proteins to forty different cell types. And so we can now make estimates of specific cell types in your body. One of the most striking finding was we looked in people with different neurodegenerative diseases and asked, "How old are all their different cell types?" And we find in this rare disease called, um, amyotrophic lateral sclerosis, or ALS, in, in the US, we often call it Lou Gehrig's disease, because Lou Gehrig was this baseball player who got this devastating disease. It's a muscle weakness that often progresses extremely quickly, and people die. Um, and what we found is that these individuals had extremely old-- an enrichment in extremely old muscle cells, skeletal muscle cells in particular, and also heart muscle cells, cardiomyocytes. So there was this very strong association, and then we looked in a progressive, a, a, in a, a longitudinal study, uh, cross-sectional, but where, where we had twenty years follow-up. It's called the UK Biobank. So we had blood samples from people when they entered their stud- this study healthy, and then a number of people developed, about two hundred and fifty, developed ALS over the course of fifteen years. And we, we found a strongly increased risk to develop the disease if they had these extremely old muscle cells.

    7. AH

      Hmm.

    8. TW

      So here we have now a, a much finer resolution and granularity where we can get more predictive power, we can get more precise prediction of what type of disease you might get. And of course, at the molecular level and the cellular level, we, we know where the problem might be, right? It's not just the whole organ, but now we know which cell type. Another one was, there's these cells we call astrocytes in the brain. We find a very strong association of the age of astrocytes and development of Alzheimer's disease, much stronger than just the brain age, so the age of your whole brain. When we look now at these individual cells, they are a very strong predictor of Alzheimer's disease, especially together with a genetic risk factor. So that's something that we have been developing and really excited about. But my ultimate greatest stimulation right now [chuckles] is to, um, build a map of the human proteome across different genetic diseases. So what I'm trying to do is to ask, if somebody has a disease that is caused by a single genetic mutation, and there's about six, seven thousand such, we call them monogenic diseases, where if you have a mutation, you will get a disease, childhood disease or an adult disease. So what I want to do is to look at individuals with these mutations and profile their plasma, basically measure all the proteins and see, are they different from healthy people? And if you do that across hundreds of diseases, you basically get a picture of how our body responds to the disruption of specific genes. And the idea is that this will allow us to look at any type of disease where we don't know how it's caused and then say, "This looks like this genetic disease."

    9. AH

      Hmm.

    10. TW

      Basically, what we've been doing in animals with worms, right?

    11. AH

      Mm-hmm.

    12. TW

      Where we knock out every gene or in flies, use the human experiment, if you will, and this may be a bit dis- disparaging, uh, these are o- obviously people who have diseases, but there are repositories where, uh, people volunteer to make these samples available for research. And so, uh, we have had the opportunity already to look at twenty-five different genetic diseases, and we find these very specific patterns. So that's what I want to build and then make it publicly available so that any researcher can ask, "How does my protein of interest that I want to study, how does it change in these different genetic diseases?" And learn about how they're related to each other and which biological pathways they may, um, change. That's what motivates me the most. [chuckles]

    13. AH

      I love it. I, I, uh, it's so clear that you're a driven person, and it's, uh, learning about what the next vista is, is, is always exciting. Um, and again, thanks for the incredible work that you've been doing for all these years, you know, bringing a level of rigor and seriousness to something that, um, prior to that, was just kind of tossed around as kind of an observation and a- and something to discuss at parties, you know, young blood and, uh, this kind of thing. You, you're clearly, um-... shedding light on, on real mechanistic knowledge and the ability to measure aging of different organs now, I think is a, is a tremendous technology. I'm very curious about that. I know a number of other people will be. We'll put links to the various things and papers, et cetera. Uh, and I also want to thank you for coming here, taking time out of your busy schedule, your lab, your family, your vineyard, this is a plural, [chuckles] to educate us on health and on health span and on the relationship between youthfulness and aging, and, um, and what we can do to, to really ameliorate the, the degradation of health span. You're developing the things that change lives for the better, so thank you so much.

    14. TW

      Thank you.

    15. AH

      I really appreciate you.

    16. TW

      Thank you so much for having me.

    17. AH

      Yeah, and come back again-

    18. TW

      It's a pleasure.

    19. AH

      -and talk about all the other discoveries.

    20. TW

      Yeah.

    21. AH

      And I'll, I'll buy a bottle of the wine from your vineyard-

    22. TW

      [chuckles]

    23. AH

      -and I'll gift it to one of the drinkers in my life.

    24. TW

      Sounds good.

    25. AH

      All right.

    26. TW

      Thank you very much.

  24. 1:56:40 – 1:59:13

    Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Protocols Book, Social Media, Neural Network Newsletter

    1. AH

      Thank you for joining me for today's discussion with Dr. Tony Wyss-Coray. To learn more about his work and to find links to the various resources we discussed, please see the show note captions. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please follow the podcast by clicking the Follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review, and you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols: An Operating Manual for the Human Body. This is a book that I've been working on for more than five years, and that's based on more than thirty years of research and experience. And it covers protocols for everything from sleep, to exercise, to stress control, protocols related to focus and motivation, and of course, I provide the scientific substantiation for the protocols that are included. The book is now available by presale at protocolsbook.com. There you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols: An Operating Manual for the Human Body. And if you're not already following me on social media, I am hubermanlab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Huberman Lab podcast. Again, it's hubermanlab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries, as well as what we call protocols in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to hubermanlab.com, go to the Menu tab in the top right corner, scroll down to Newsletter, and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Tony Wyss-Coray. And last but certainly not least, [upbeat music] thank you for your interest in science.

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