The Transcript
Chris Wood:
Hi, ladies and gentlemen, we are here in Puerto Rico at John Mauldin’s house for his birthday. It's beautiful outside as you can see, a little warm. But I'm here with my colleague, Patrick Cox, and my collaborator on Transformative Age, and we're just going to talk about what's exciting Patrick today. And so I guess, with that, supplements, exercise routines, what are you doing? We can start anywhere. We were just talking about vitamin D, actually. I don't know if you want to start there or what.
Patrick Cox:
Let's start at the beginning. Basically, I'd like to sort of explain why we know age reversal is real, and then talk about some of the ways that we can marginally reduce our biological age. The reason we know that age reversal is real is the fact that when you were born, your parents were old—so the gametes, the spermatozoa, and the ova that created you, in fact, were old. Nevertheless, by the time you came out of the womb, you were young. So what happened?
Well, we actually know at this point that as soon as that zygote, which is before... The embryo is attached to the uterine wall, but the zygote is when these two genomes actually merge together in this unique genome, never before seen, newly created, 3 billion base pairs of genes, 6 billion total. Somewhere in that genome is the information needed to not just analyze this new and quite flawed zygote, because cells replicate every time spermatozoa or ova… they have epimutations, which is just replicative errors. So the first thing that happens to you once this new, unique genome is created, is it undergoes a profound process of age reversal. Otherwise, we wouldn't have-
Chris:
Babies.
Patrick:
Yeah, correct. Life would end in a couple generations. So we know that that's going on, and we've proven it now on the basis of molecular biology, which I won't get into. You don't need to know that. All you need to do is understand the implications of having young children. So things have happened in the last few years, beyond sort of the molecular biology, looking at things on a very minute scale. One of the most important was Valter Longo's fasting-mimicking diet, where he put people on a very calorie-restrictive diet for five days, and animals as well, and what he saw was the activation of some of these embryonic pathways. So it's not just during the zygote, but it's also during the embryonic period, which lasts about eight weeks until you go through the embryonic fetal transition when you become an adult, which is nine weeks into your life.
We know that these pathways are still accessible. He showed in animals and people, even animals with type 1 diabetes that don't have islet cells so they can't manufacture or store insulin, were regrowing islet cells. And in humans going through this as well, you see the markers showing they're going through that same thing. So that's a profound age reversal though it's not permanent. But what it indicates is there are ways to activate that original blueprint that reversed the age of you as a zygote, and then as an embryo. And it turns out, quite to my surprise actually… I've been focused on the big age reversal biotechnologies, partial reprogramming. Google, Amazon, Jeff Bezos have now invested $5 billion for this process of using some of the so-called Yamanaka genes. In eight different species now, we've seen that if you use those, you can take an animal that's the equivalent of a 70-year-old in human terms and turn it into 30. You can extend their lives, fix their health, but that's a long ways off.
The other one is telomere elongation. So Leonard Hayflick discovered that cells have limited replication because when you run out of telomeres, which is like the thread of life, the Greek goddess Clotho, snips it... when that happens, you're essentially dead. I mean, you suffer first, and then you die. So we've known for decades that if you could elongate telomeres, then you're going to do away with maximum lifespans and improve health. And it was just universally accepted that the only way to do that was with genetic engineering, using viruses or some other mechanism.
Well, in the last six months, two different groups, one from Johns Hopkins, which is by far the most prestigious biotech research group in the world, and the other, MD Anderson, have identified drugs that in human cells and animals, extend telomeres.
That will be the singularity, I think. John von Neumann, when he invented the term, wasn't talking about AI. That came later.
People interpreted what he said, which is that something's going to happen beyond what we really can't predict the future. It's going to change human society so much that we can't make accurate forecasts. And I think that it is significantly extended healthspans. And so both of those technologies are coming, but we don't know how far they are away.
So three and a half years ago is when I started working with Mike Roizen, the co-chair of his scientific advisory board and the chief scientific officer, and my job essentially, because everybody else on the board is doctors or are doctors, depending on if you're British or American, how you would say that. So doctors have a particular incentive structure, and they have to be careful. They cannot say something that hasn't been proven. I'm a macroeconomist. I make predictions. That's what economists do.
You say, “In these situations, this will happen.” Whereas a doctor tends to say, "Is there long-term data?" and I'm using Bayesian analysis, “Is it safe? Does the mechanism of action make sense? Does it work in animals and cells? And is there reason to believe that these gene pathways being affected are what they called conserved,” meaning they exist in people as well as dogs and other animals. So if we have really positive data, I'm willing to say, "You should probably try this. I think it will work. I'm taking it." We may find out for some reason that you shouldn't later on, but given how important it is at this point in history, especially for those of us who are older… I mean look at these kids running around, I don't think there's any chance, that barring some civilizational disaster, that they're going to be part of the first generation to live many hundreds of years. But people like me, and John's birthday, being totally appropriate for this conversation, we don't know if we're going to be part of that generation or part of the last generation to live this truncated lifespan.
Off-Camera Party Attendee:
Hundreds of years, this is why you need to be a rational optimist.
Patrick: Actuarial scientists have made the calculations in terms of life expectancy if you just take age out of the calculation, and one study says given that everything is the same, now we would expect behaviors to change. I think some people are going to become more reckless, some people will become more careful, but something will kill you eventually. And their estimates are our average lifespans will be six to 700 years,
Off-Camera Party Attendee 1:
If you think about it, 80 years ago, people thought that living to be 80 was a rare occurrence.
Patrick:
Yeah, and it's exponential.
Off-Camera Party Attendee 2:
I'm going to be very careful with my IRA.
Patrick:
No, seriously. Seriously, that's true.
Chris:
What, in your mind, is kind of maybe the easiest thing, in terms of either-
Patrick:
Well, I'll give you one-
Chris:
For longevity, basically.
Patrick:
That almost everybody can do right now, and then several supplements that are relatively new. A lot of scientists have been saying that the last 10 years has produced as much knowledge as all previous. And that happens all the time. From any point in time, you can measure back 10 years. And what we know, mostly because of the advent of microelectronics and computers and stuff like that, it’s just increasing so fast we really can't keep up with it. But one of the most interesting things that you can do to get really profound impacts on health is heat shock therapy. So we have in our body, these heat shock genes which activate autophagy, eliminate misfolded proteins, and are able to prevent the buildup of just stuff that you don't want in your body.
Chris:
So just real quick, to go back to autophagy. It's like a cellular repair process, a cellular recycling process?
Patrick:
Right, right. So we have lysosomes, these organelles, which I think of as the aliens in the film franchise. They're filled full of acid, and they have the ability to engulf anything that shouldn't be there, from viruses to garbage, and just dissolve it and recycle it. Autophagy means self-eating, and so autophagy is really an important part of maintenance. If you don't have autophagy, and that's the case for people who don't exercise or who eat 18 hours a day, especially highly processed carbs, then you never really enter into an autophagic state.
Chris:
It's not good to be comfortable really, I guess? I mean, yeah, in a way.
Patrick:
Yeah, that's a theme that has emerged in so many of these therapies. Really, what we're trying to do is reverse the effects of modernity. Because we never get cold, we never get really hot, we never get hungry, and we don't bleed—all things that everybody did on a regular basis before. And who would've guessed that they all have terrible consequences on our health? We are adapted to do all of those things.
Heat shock therapy was pioneered by the Scandinavians who had just come to the conclusion that saunas were healthy. And it turns out they're absolutely right. But even before they had the data, multiple Scandinavian countries had done huge studies looking at the effects of various types of saunas, and how often you do it, temperature, all that kind of stuff. And if you're taking a sauna a day, like a lot of Scandinavians do, you can reduce the risks of Alzheimer's, heart disease, all causes of mortality, which just means death, really significantly, probably by more than half, which is going to have a huge impact in your life.
Then the Japanese picked up on it, and they started researching, which I think it's called Waon therapy, but it's a near-infrared. So every Costco sells these Waon saunas, near-infrared saunas, and you do the same thing with that. It's a little bit different protocol because you don't get quite as hot as you do in a sauna, but I love the fact that the most efficient heat-transfer medium that we have is water.
Chris:
Okay. Hot tub will work, yeah.
Patrick:
Hot tub will work, a hot bath will work. So if your water heater is set at high enough temperature... When we bought our house, there were small children, so they turned it down so they wouldn't scald themselves. We turned it up, so I can fill a tub and get 110-degree water. And you don't need that hot, but it really does the trick, and it does it better than a normal sauna, with the added benefit that the few incidents of injury come from overheating the brain. And if you're in a bath, a bathtub with your hands and feet underneath, because we have heat transfer, the ready of [inaudible 00:36:01] and in the palms and our soles, then your head is not going to overheat. So the bath is actually a superior heat shock therapy technology. And I've run the numbers, it's actually cheaper than running a sauna. So it is just a question of taking the time to take it. It takes about 20 minutes. And you know if it's working, because-
Chris:
That's what I was going to ask.
Patrick:
At that temperature, and it might be less for you. I mean, Mexican scientists have used 105 degrees, which is kind of a typical hot tub. It takes longer, but you get the same effects eventually. 108, 110 degrees, it starts out feeling kind of good, even though... If you're not used to it, you think you're scalding yourself initially, you're not. But by about 10 minutes in, it's no longer fun, and you switch from producing endorphins, which make you feel good, to dynorphins, which you're telling you just to get the hell out. So despite having me doing hot baths regularly for years, by the time it gets to 20, or if I go longer, which is probably desirable, 25 minutes, my body is just screaming to get out, escape, get out, then I do, and I lose at least a pound.
Chris:
Yeah. So if you start sweating, is that a sign that okay, it's probably working a little bit at least, or is that your-
Patrick:
Yeah. Panic is probably the best, but... Sorry, I lose at least a pound of water, and my heartbeat gets up around 130, 140, which is the same as relatively intense exercise. So I take a pulse oximeter into the bathtub with me, just to make sure that I've got my heartbeat up. So you get out, sweat for 20 minutes. I do it usually laying on the bed listening to music. Most people have bathtubs, most people can do this. And at some point, I'm sure we'll cover this in the newsletter and give people some more data.
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Chris:
A new one I wanted to touch on, I just started taking spermidine, and I'm not entirely sure exactly why. I've read about it, that it's good. But I know you're a fan, but it is kind of expensive for some folks. But I'm wondering if they can't take a supplement of spermidine, and why it's good, and maybe if there's some foods that are cheaper that we might be able to hit on.
Patrick:
Yeah, absolutely. So spermidine, as the name indicates, comes from “sperm” meaning seeds. It's a necessary nutrient for, not just seeds, but all gametes. So it occurs naturally, where in stem cells… if you look at the data in terms of population groups who eat the most spermidine in their diet against those who don't, the effect is so profound. I mean, it really rivals exercise.
There's only two new supplements. I mean, if you're niacin deficient, and then get it up to normal, it had the same kind of an impact. But yeah, so spermidine is... I don't know why it's so expensive, because a couple tablespoons of a wheat germ contain pretty much the optimal dose. Most nuts have it. My favorite seed is the coffee bean. That's a seed. That explains why decaf has health benefits as well. It's not the caffeine though. Caffeine has benefits, it bolsters the blood-brain barrier. It's good for you. But coffee is a really good source, and I think it explains a lot why the people who drink the most coffee have lower disease rates, et cetera. By the way, spermidine is heat-sensitive. So if you want to optimize your spermidine coffee content, get lighter roast and use cold brew. Cold brew is fantastic. It's the best coffee there is.
Chris:
It tastes better, I think.
Patrick:
It does taste better. It has less acids. I don't know why anybody would drink any other kind of coffee. So that, some nuts, and I usually put a tablespoon or two of wheat germ in something I'm eating, usually Greek yogurt, because I'm consciously-
Chris:
Because I thought mom, my parents were crazy for feeding me wheat germ when I was a little kid. I was like, "That stuff's gross."
Patrick:
I know, it used to be a big deal, and then it just disappeared. But they were right. They were absolutely right.
Chris:
Interesting.
Patrick:
Another one, by the way, as long as we're talking supplements that anybody can do with a food source, even though I take the actual supplement, is ergothioneine.
I'll give you some inside baseball. I was a macroeconomist, policy economist for decades, and one of our heroes on the more freedom-oriented side of the debate, is Bruce Ames, this chemist, biologist at, I guess he was at UC Berkeley. And he became very wealthy by creating the Ames test, which is essentially a Petri dish. You put something in it, and you can determine whether or not it has any carcinogenic properties. Well, as soon as he releases this, all of these agencies, I'm trying not to insult people, I don't want to get too political here, started saying, "See, this is a carcinogenic, ban it now." And so there's this... They're going to ban all the things. And so Bruce Ames had to come forward and say, "That's nonsense. I invented this. Lots of things are not harmful at low dose and harmful at high dose." As a matter of fact, there's a hormetic effect, lots of things are actually very useful and healthy at low dose, and bad for you at high dose. So he ended up being the primary spokesman against the use of his own device.
So we all followed Bruce Ames, he was a great guy. He spoke at a lot of conferences, and then he disappeared. And the reason was, when he was coming up with arguments against using the Ames test to test for carcinogens, he said, "Look, what you're talking about is, in effect, much smaller than being B-vitamin deficient. Before you start banning things, why don't you get people to start taking the essential nutrients?" And so that got him started thinking about this, and he came up with this concept of longevity vitamins.
So the definition of a vitamin is something that if you take it away from animals or people for a certain amount of time, it will produce bad side effects. Well, what he figured out was that a lot of nutrients that we take don't have any short-term impacts, that they're all long-term. They're associated with healthy aging. And a lot of nutrients have two pathways, uptake pathways. One is used to get you to the point of reproduction. It's useful when you're young, and it always takes priority away from the much slower, low-dose process that is utilized for healthy aging. And so he's the guy who made taurine, which is now a big fad.
Chris:
Yeah, I was just taking that also, actually.
Patrick:
Great data. In animals, it outperforms rapamycin in terms of lifespan. But the other one, I think, the most interesting is ergothioneine. And ergothioneine, it's very difficult to test to see if it's a vitamin, because it's in everything. I mean, if you look out, anything green, including surface waters, has ergothioneine in it because the bacteria at the heart of our basic recycling, the organic processes, I can't remember the name of the bacteria, they produce it. And therefore, even in cell cultures, they have ergothioneine in them. So you can't eliminate it without going to amazing lengths, but that's not enough to get the anti-aging effects. Fortunately, mushrooms are a fantastic source. And so if you look at populations, and grade them by the amount of mushrooms that they eat, it almost a direct correlation between lifespan and ergothioneine consumption, except for Ireland, where some of my ancestors come from. I think it might have something to do with alcohol. I'm sorry, I don't mean to offend my brothers, but they're still much higher than America, which is a low mushroom-consuming country.
So if you are getting to the point where you're getting about five milligrams a day, like the Italians, the effect of that is, like spermidine... I mean, it rivals exercise, which I never thought we'd ever have anything that is going to give you the same kind of benefits of doing cardio and resistance training.
Chris:
So Patrick, thank you so much for doing this. I mean, despite all the reading I do, and research, every time I talk to you, I learn some incredibly fascinating stuff, so I really appreciate it. I hope everybody who's watching this liked it too, and we'll have a lot more to come. And remember, Patrick's contributing every month to Transformative Age, and he's bringing some amazing stuff to the table, so thank you very much.
Patrick:
Thank you, Chris.