B (3:50)

I am not. So it's so I don't have to disclo knows that I'm not.

A (3:55)

Well, given how it is performed, I think at some point you will wish you were or you probably when it goes public you will be able to be. But as you look right now, what's the most. There are two things to it. What's the most exciting area right now as it relates to longevity and health. And then frame that in back to what I know Mike Roisin stands for, which is not the fly by night trend, not something you can do tomorrow that's going to improve your health in the long term, but the back to the basic six and the things that you need to do on a day to day basis to take care of your own health. But start on the excitement and what you're seeing out there today, Mike.

B (4:36)

So when we wrote the Great Age reboot and when I was on your show with the Great Age Reboot, there are 14 areas of research into the mechanism of aging, what causes aging, that we're showing in each in two animal species that they could turn the equivalent of a 90 year old person into the equivalent of human 40. That's really, I mean when you think of it, it makes AI look as a small disruptor. If you're going to be able to be younger than your kids, it's emotionally tough to capture that. Well, in the last two years all of those have progressed and now five of those are in human trials. When you say five of those are in human trials with 14 shots on goal, but five in the immediate shots, it looks like we're going to get a likely breakthrough. The most exciting thing is we're learning a lot more about the mechanism of aging due to the exponential reduction in cost of understanding the human genome. Let me Joe, go and relate that in Peter Linnemann's terms and your terms. When the human genome was first uncovered, it cost $3 billion and 10 years. That's now $40 and six hours. So an 8 to 12,000 fold reduction in the time and cost of doing science. The second part is the most exciting of the current things I think is on brain wellness because obviously your brain is what you are, what we're learning. Even last week studies on Tau217, if you will, ratio of 2 of the Tau217:1 unphosphorylated to the phosphorylated predicted when we can tell each person when they will develop Alzheimer's disease, if and when they will develop Alzheimer's disease. And that's modifiable now it's modifiable by 40 things that each person can do, if you will. One of those is one of the age related things I.e. therapeutic Plasma exchange where you can literally reverse the cognitive dysfunction and prevent it as well. Another one is the brain games Freeze Frame and Double Decision. You know, when you do crossword puzzles or if you will, even, even doing, you know, any game on your computer, you think you're improving your brain, but it turns out not. The brain is much like the heart or skeletal muscle or your bones. You have to injure it to turn on the repair genes. And the only way apparently we injure our brains is forcing it to work at maximum capacity, which is the, if you will, the speed of Processing games called in Double Decision and Freeze Frame. A month ago almost exactly came out with their 20 year data on preventing dementia. Just 18 hours of practice over 10 years, that's what an hour and a half or two hours a year reduced dementia by 40 plus percent. This is randomized controlled trial. Very well done study. Every one of the people tuned in can afford to either get a speed of processing game three or get the actual games that showed that they not only decrease dementia but they increase acetylcholine production by this repair mechanism in the key brain areas, executive function and memory.

A (8:59)

So what do you do in that process? Do you go to a studio and take a test? How do you get your brain running at that rate?

B (9:07)

You. You. This is. I have no. I wish I did. I have no financial interest in Brain HQ either. Whoop should put it on their app for free or as part of a subscription. But you can subscribe to Brain HQ or you go to Speed of Processing games at Brain hq. And the games they tested were Freeze Frame and Double Decision and they tested them against people doing solitaire and the other speed, if you will. The other games on the computer, those were the control group. And compared to the control group, same group of people age 73 to 93. A 40 plus percent decrease in dementia from just 18 hours of practice over 10 years the first 10 years or 25% if you get lazy and just do 10 hours of practice.

A (10:04)

It's interesting about your comment about it doesn't heal unless you break. Makes me think Mike about I was reading in Peter Attia's book Outlive about lifting, lifting weights and the fact that there is cognitive improvement from weightlifting, but only if you are doing very high weight. And so in other words, you need

B (10:31)

to do for high weight for you, not in other words, each person is individualized for high weight.

A (10:38)

Understood? Yes. But to, to 75 to 90% of your threshold weight for you as an individual. So obviously we're not talking about Willie Walker trying to bench press £250. But the point being is that if my bench press is 150 pounds, I ought to be doing 75 to 95, 90% of that to be able to get the cognitive improvement from it. And one of the things that I have struggled with on that one is that I don't want to, I don't want to bulk up, I just want to use my muscles so I do lower rate, lower weight on higher reps than trying to bulk up by doing higher weights and fewer reps. But, but, but I won't pick up per what I read in Atiya's book, I won't pick up the cognitive benefits of doing that off of higher weights. And so I just hearing you talk about these cognitive tests of not just sort of keeping your mind active and reading the paper, but having to really put it into kind of the gauntlet, if you will, in high stress environments is, is very interesting about how the body works, how the body grows and how the body retains its capabilities.

B (11:44)

Probably everyone in commercial real estate puts it into that gauntlet right now if you will. From what I understand, you know, my knowled that field is little. But the point is that when you injure yourself, for example, jumping 20 times morning and night on a hard surface, injure your bone, you turn on a gene in that bone that makes that bone stronger. So remember someone said, and I wish I can remember who said the quote is what doesn't kill you makes you stronger. Well that's true for muscle. So the reason you build muscle is you injure it. When you do that 812 repetition at 75% or so of maximum capacity and then you turn on a gene, that's why you have a day in between, you turn on a gene that repairs it. So it's stronger. That's the same thing. Now muscle has something extra and we think it is for muscle memory. That is you also turn on a gene in the muscle that produces a small protein. The name isn't particularly, it would say Risen, MIT and Mass General tried to patent it at the same day as UCSF tried to patent it. That's why we know a lot about it. But a Risen goes across the blood brain barrier and turns on a gene in your brain that produces brain derived neurotransmitters, trophic growth factor that builds the memory center. And there's only, you know, Willie, you understand this. There's only one organ in the body where size matters and that's your hippocampus, which is your memory center of the brain.

A (13:35)

So Mike, as we're talking about the brain, a couple of the other sort of trends that have come out since the two of us spoke were one sauna and the other cold plunge and sauna. From the reading that I have done, and most of the studies have been in Scandinavian countries, but people who do sauna for 20 minutes a day on a consistent basis have shown that they diminish the rate of both dementia as well as Alzheimer's significantly. Am I reading those research reports properly? And is that something that you and your team have looked at as it relates to how people can sort of hack into longevity on brain health?

B (14:16)

You're right and I should give Credit. There are 10 of us who are on the scientific advisory board of what we call4yngevity.com and we go over all the data, review it periodically and so sauna and cold plunge both work on the same mechanism. So we think you can do one or the other and get the full benefit and not both, but they both preserve heat shock protein or turn on heat shock protein. Don't have to know the name obviously, but what it does is it protects your proteins from damage. So the reason that therapeutic plasma exchange works to reverse long Covid symptoms, COVID vaccine injury, reverse Alzheimer's dementia, reverse early dementia and Alzheimer's in randomized controlled trials is because the proteins it gets rid of are Ms. Signaling. What cold plunge and sauna do is they essentially they envelop your proteins to protect them from learning how from being affected by other things that will cause them to miss signal. It is the same mechanism. And so Willie, if you like sauna and that cold plunge, just do one or the other. That may be self serving on my part because I enjoy sauna and cold plunges are not fun for me.

A (15:55)

I have to tell you, I do both on a very consistent basis and am fortunate to have both in my home. But I will tell you, Mike, when I first started doing the cold plunge, I thought I had to be a macho man. And so I dropped the temperature down to the low 40s, and I. And as I would walk by the cold plunge after working out, I would find any excuse on the face of the earth to walk by it, and I'm too busy. I got to get going. And I found myself constantly finding an excuse not to jump in. And then I heard a podcast by Tony Robbins where Tony Robbins said he cold plunges every day at 56 degrees. And I texted Tony, and I said, Tony, you do 56 degrees? He says, yeah, all you got to do is do it. He said, it's to wake up the body, and to your point, it's to protect the proteins. But he said, you know, all the studies say that you don't have to be in the 30s or low 40s to be able to get the benefits of cold plunging. So I have mine today at about 48 degrees, and it's plenty cold. But at the same time, I can. I can do it, and I don't avoid it like the plant.

B (16:57)

Tony was exactly right. I gotta tell you. Tony was exactly right. The Data would say 1 degree below 57 is enough, and it's 17 minutes a week gets you the full benefit.

A (17:11)

Oh, that's. That's great to know. So, Mike, one of the other things out of your research that's very clear and kind of staying on the brain, and then we'll move to diet and we'll move to sleep and all the other things that I love to talk to you about, but one of the. One of the greatest agers by your research is stress, and it's the greatest

B (17:31)

ager, not one is the greatest.

A (17:34)

Okay, so given that we are in challenging times, we've got a. We've got a war going on in the Middle east right now. We have an economy that feels very strong to some and feels very weak to others. And, you know, I have a son who's graduating from college. And he and I had dinner two weeks ago, Mike, and he turned to me and he said, you know, I'm kind of stressed, dad, about going into the workforce and kind of getting on with my life. And then he said, you know, but in comparison to all the stress that you carry running your company, I kind of don't, you know, I can't kind of be that stressed. And I. And I looked at him and I said, well, Jack, I've got 35 years of dealing with my stress. You know, you're. You're just coming into the stressful part of your life, so don't worry. You have every right to feel and carry that stress. The one other thing I said to him, Mike, the one other thing I said to him, which I. Which I stole from my guest last week, Sahil Bloom, where he reminds people as it relates to their lives and the ups and downs of one's life, is that if you're living your dream, there's nothing to get upset about. In other words, like, I live my dream every day. I wanted to build this company to be the size and scale that it is. And while clearly there are curveballs that I get and ups and downs and days that are great and days that seem less great at the end of the day, as long as I'm pursuing my dream and living my dream, what's to complain about? And it was fun because my son Jack was sort of like I said, you went to the college you wanted to go to, you studied what you wanted to study, and you're heading out into the workforce to go do what you want to do. There should be no stress there, buddy. And he was like, that's a great way of looking at it, dad. But anyway, on stress, how do we get it out of our system? How do we. When we're confronted with all that's going on, what are the things that you do personally that can be helpful tips to people to sort of say you meditate, you go on walks, you.

B (19:20)

How do you.

A (19:21)

How do you get rid of the stress that so many of us carry with us?

B (19:25)

Well, there are three keys, and you have named one of the three major ones, which is three Ps, posse, purpose, and play. So the purpose is you're living your dream. I get to live my. This is ideal for living my dream. I want to help people live younger, longer. And so this is perfect. So thank you. The things you can do are, I call six people who are friends every Sunday, because the data from long ago in the Whitehall studies in the 1950s has been reaffirmed multiple times. The most important thing in reducing stress is having a posse, friends who support you. And as we get older, especially if you retire, you lose those work friends, you lose your school friends. So it is making the effort to call and generate those friendships again. The third thing is play. And whether it is with your grandkids or with your kids or with in squash or pickleball you know, squash is my game. So whether it's squash or pickleball or whatever it is that play that focusing on another thing, when you're in a pickleball court or on a squash court or tennis court, you can't focus on anything but the game because it's going to get you if you don't. So you focus on that. That clears your mind. All of the other techniques, whether it is meditation or resistance breathing, I should have brought that out. One of the things I do every day is 10 double breaths. So the second most important muscle in our body that we often don't strengthen is our diaphragm. And so if you breathe through a device that limits your breath in, looks crazy. So, so I'm going to do it. And you have a straw out here, a double breath through a straw. And you narrow that straw orifice. It's called inspiratory resistance trainer. And doing 10 times but putting your finger on your belly button so you're focusing on your finger. So when you do that, your finger should go out, that most of our fingers go in because we breathe with our chest and not our diaphragm. That's why you want to strengthen your diaphragm. You know, it's strengthening your lung functioning because you're actually teaching your diaphragm to move down. So you do it. If it moves in, don't worry. Practice getting it to move out. You will be able to. And as you narrow the orifice of the inspiratory resistance trainer, you strengthen your diaphragm. And so you get. It's a double, it's a twofer. I like. You know, it's. You get two benefits. You not only meditate or get focus on stress relief by doing that, but also you in fact strengthen your diaphragm. And it's. And I like to say that driving in traffic is one of my most stressful things. When someone cuts me off and what I do is I put my finger in my belly button and double deep breath. And a much better thing to do with my finger than what I used to do.

A (23:03)

So, Mike, when you talk about the posse and relationships, clearly from the Harvard longevity study, it's very, very clear that the social networks that people have are one of the key drivers of longevity. But there are a lot of people who are using AI to create a one to one relationship with AI bots and with their grok friend or their anthropic friend or whatever you want to call it. Any research or anyone looking at whether those types of relationships are similarly stimulating from a socialization standpoint to just you and your eight friends that you call every Sunday.

B (23:46)

Yeah, well, you're in. I call different ones so they, I, I add to my potential network every Sunday. But the. You're in Philadelphia, I think, or I'm

A (23:59)

going there tomorrow to see Peter.

B (24:00)

But today you're watching with Peter. You probably are. Will be. So at the University of Pennsylvania they have a large group that's studying this on what AI friends do. And so we don't have data on it yet, but I don't see, think, and this is an interesting concept is, is the support, is the posse support because you know they will come to your aid if you need it or is it just the, the feeling of that whether they will or not, if they're a AI friend? I don't know the answer to that, but we'll get the answer within a year or two from the University of Pennsylvania or other people who are probably studying it as well.

A (24:46)

I think it's, I think it's a fascinating concept and quite honestly, given the value to me of my friendships, I'm sort of hopeful that it comes back and says you don't get from the chatbot what you get from the human, human friendships. I mean it feels like the chatbot's going to take a lot of things away from us. Keeping the, keeping the importance of the personal relationships, at least from my perspective, would be really great. But the one, the one other thing

B (25:11)

I think that's true because I think it is that we have to have know that some of those friends, that is the posse part of the friendship, will come to your aid, will be there when you need them. And so I think that's an important component. Yeah.

A (25:28)

The one other piece to it though is that there are clearly people like you and me that have our own posses and then there are plenty of people who don't. And one of the things that you write about and talk about is, is tips for people who might be feeling a little bit isolated. And so the, the one thing there is that clearly if there is some therapeutic effect of having a chatbot who you engage with on a day to day basis for certain people who are more isolated than others and don't have the luxury of a cohort or a posse to go to, it could be extremely beneficial if it turns out to be so.

B (26:05)

Yes, but I think it may be somewhat beneficial. But again, whether you're joining a club or taking a new class, whether the class is online or not. You find that at the Cleveland Clinic, we have this wonderful system called social prescribing. If someone is lonely or has loneliness, we can actually social prescribe them to something they want to do. And one of my favorite patients, if you will, I still see patients on Thursdays and Fridays. And one of my favorites was an art teacher, an artist who came back to Cleveland to care for his mom. His mom died and he had totally focused on her, had no friends. So we use social prescribing. Hooked him up with a. A student art class, and now he teaches. So the students became his initial posse and then the other teachers and the other artists. And so he's now got a. And he's. He's taken up bike riding and he's now got a group of bike riders who also are as part of his posse. So social prescribing is a great thing. That is find another group to join.

A (27:22)

I'm certain that you just sit there and see what he is doing today and see the years adding on to his life as he sits there and engages in the way that you're describing it.

B (27:30)

And he sees them, too. I mean, that's the great thing.

A (27:33)

Yeah. Mike, let's talk about food for a moment. I've changed my life a lot since I got to know you. And one of the things that I have had a little bit of a challenging time. I eat a lot earlier today than I used to because of you. I don't always eat when the sun is up, which is something that you do. Talk for a moment about. Some of the helpful tips as it relates to food, of both what to eat and when to eat that people listening in can benefit from.

B (28:05)

So I'll get to the. There are only five foods that aren't healthy for us. Simple sugars, added syrups, and simple carbohydrates or strip carbohydrates. That is things without their, if you will, fiber with them. Those raise your blood sugar fast. And the value, if you will, we're now learning, you know, I'll break and just say something weird for a second and then come back. Remember Oprah had this great show. You get a car and you get a car and you get a car and you get a car. And it saved Pontiac for a number of years. But in any case, we now in executive health say you get a statin and a GLP one. You get a statin and a GLP one, you get a statin whether they need it from a standpoint of cholesterol or whether they need it from obesity because the side effects are so good. The side effects of the GLP1s are to do something metabolically that lowers that sugar effect. So it is simple. Sugars in your blood change your proteins and how they function. And that's what we. The problem is the simple sugar. Simple like that is added syrups, simple carbohydrates, red and processed red meat, and then fried food. If you eliminate those five, virtually everything else is fine. And you want to find food you love that loves you back. So food is a relationship like a marriage. You wouldn't marry someone who's going to kill you. You shouldn't eat food that's trying to kill you every day. So just avoiding those five foods, everything else, you'll find something you love. The timing that has been shown repeatedly is that if you finish eating three hours before you try to go to sleep, one, you'll sleep much better, two, you'll have more energy the next day, and three, you won't feel as hungry. So you actually lose weight better if you, if that's a goal or stay thin better. And so whether it is the process of fasting, meaning you have a longer period without food, whether that holds because you're reducing your calories or you've got a longer period before you go to sleep, we don't know why it is effective, but it is that three hours. You want to finish three hours before you lay down, you go to sleep. Sleep. Which is why I say eat when the sun is up or only eat when the sun is up.

A (30:58)

And on the fasting front, I don't think you don't. You don't consider if you have dinner at 6pm and don't have breakfast until 9am the next day. That's not a, that's not a form of fasting. You do full fasts where you don't eat for an extended period of time, correct?

B (31:14)

Well, I do, I do 14 or 16 hours a day. And, and, but the key is I do what is called the fasting mimicking diet five days a month. A wonderful research. Head of gerontology at usc, Walter Longo and his group accidentally started to find out the benefits of this. I think it was in 2017, may have been 2015. I've been doing it ever since. So I read the, the abstract the day it came out by accident. It was, he said, 1,000 calories, day one, 750 the next four days. And initially it was for the animals, for initially in the first human trial, I should say it was a tomato Corn based soup. And I still go with that. But it was initially they did it in mice. The mice they were doing it with was calorie restriction. But someone fed them after five days of calorie restriction and it turned out they regenerated every biomarker that showed less aging by doing that much better than calorie restriction did. So five days a month of 1,000 calories the first day, 750 for the next four days. And the soup diet is 36 ounces of diced tomatoes, 12 ounces of corn niblets, 48 ounces of water, onions and spices to taste. You can literally have as much of that as you want the next four days and then you resume. A diet without those five things is essentially a Mediterranean diet. And that resets every aging marker we know of. It's pretty simple to do. I've been doing it, whatever it is, either 7, 8, 9 years or 11 years literally the week it came out. Now the first test in humans was in graduate students because they'll do anything. So they did it with bone marrow biopsies and showed it, reversed it. They then did it. That was 25 to 30 year olds. They did it 35 to 40 year olds. He then did in 65 to 70 year olds. He then did 85 to 90 year olds. It works in every group. It works to prevent cancer recurrences as well. It's a brilliant diet for Walter. Walter Longo should be taking incredible credit for it. But it really is something that helps you reverse every aging marker. Now you have to do one more comment on it. On days four and five, you can't do hard exercise, so you have to time it. If you. I do. If you will cardio and weights three days a week. You have to time it. So days four and five aren't days when you'll do that because otherwise you'll, you'll feel great on doing the first ten minutes of whatever you're doing and then it'll be a real struggle. So do those on days one, two and three of the, of that program.

A (34:30)

And what happens when you get invited to dinner on Wednesday?

B (34:36)

I plan, I plan the week so that I pick a week when I'm not doing anything other than I can do that, you know, I circled on the calendar. My wife knows it. You know, it's. It is. I'm not going to travel because it's hard to do when you're traveling to take the soups cans along with you. But other than that, I do it.

A (34:57)

Does she do it with you?

B (34:59)

Yeah, she's beginning to, she, she, you know, she, I should say she retired June 30th. She's, she was a division chief at Case Western Reserve. She wrote, she co wrotes that, the lead book in developmental pediatrics out of Hopkins every year. But she retired in June 30th. And since June 30th, she's picked up all of the, all of the aging habits. She decided this was her time to stop aging too.

A (35:35)

You and I have spoken about alcohol before and previously you said there are only five foods that you shouldn't eat because they're doing big damage to you. You've discussed at length the, the damage that alcohol does to us. Yet you are not somebody who says, you know, don't have a glass of wine. You, you yourself from time to time have a glass of wine. How, how have you, if you will manage the alcohol intake? And what would your words of advice be to those listening as it relates to how to manage it?

B (36:08)

There are two things. You want to enjoy it and you want to enjoy it with friends. The difference is every one of the studies didn't take into account the stress relieving benefit of building a posse. As long as you're not drinking alone, you're doing okay. And as long as you're limiting it to two 5 ounce glasses of wine at a time, you're doing okay. And the data would say at most three or four nights a week, not more than four nights a week. And that data shows a slight reduction in all cause mortality. That's where the red wine effect got its name. But because it does decrease all cause mortality, increases brain age, increases aging of your immune system, so increases your risk of cancer a little bit, increases brain aging, decreases cardiovascular aging. Since most of us die of cardiovascular aging, that's a way you can justify, if you will, doing it. But it is the socialization and again is building that posse is the most important thing you can do for, for your whole body, including your brain. And so have that one glass of wine, make it the best wine you can have. That is do it as a special thing and with special friends. And then I think, at least I justify it for myself, is okay.

A (37:44)

It's interesting. I, I decided to do a dry January and then I decided to do a dry February. And I'm onto my dry March now. And one of the things that I'm seeing, Mike, is that my, I haven't changed anything other than that. And my, what would you call it, My, my aging reversal, if you will, via My whoop strap right now, after two months, is starting to accelerate backwards. And it's been pretty static, if you will, for the past couple of years as it relates to my real age by the whoop strap, not by your test, which people can go online and take your real age test, which I do think is this is a great proxy, but I think the real age test that you have people do is actually probably a more specific indicator. But my whoop age is about 50, and I'm about to turn 59, so I'm about nine years per my whoop age younger. But it's interesting because it's starting to go backwards quicker than it was previously. And the one big change that I've had in 2026 is just not drinking.

B (38:47)

Yeah, the real age test. As you know, I was at the University of Chicago as a chair of a department, and I got to care for seven Nobel Prize winners as head of Executive health. And one of them was Gary Becker, who did the net present value of investments. And so what real age is, is the net present value of your health choices based on disability and death risks and death rates. That still is the most. And so I'm plugging what you said, plugging my own thing. We don't own it anymore. We sold it. But the actual age test, which is the simplified version of it, the real age test is 181 questions and goes into everything. It does the net present value very well. But we sold that in 2006. But Gary Becker worked with me on both that and the actual age test. The actual age test is 35 questions@4yngevity.com, but it has the most accurate receiver operate curves of any of the aging biomarkers. It still is the best at predicting disability and death. So I take a lot of pride in it. But it's really Gary Becker, the net present value work that he did.

A (40:11)

Have any life insurance companies tried to implement that to get a, get a. Get a forward look on the people they're insuring.

B (40:18)

So I can tell you Allstate did a test with it, and Swiss Re, I think, does use it. But Allstate did a test with it way early on, probably in 2001 or two. And the problem they had is when they told patients their real age, they wanted the insurance rates of that age person. And so their premiums, they said if they adopted it, full sport would go down. So they decided not to institute it. But a few years later, as I understand, Swiss Re does use it.

A (40:58)

It's interesting, years ago, when you And I had spoken, we talked on this topic and I went and did my real age test and then I went and looked at my life insurance policy and realized that if I lived as long as it was projecting that I would live, that the life insurance policy would be worthless. And so I actually stopped investing in it. And so so the point there is that if, heaven forbid, I get whacked walking across the street this afternoon, my poor sons aren't going to benefit from the life insurance policy. But if I live as long as I think I'm going to live, I'm glad I'm no longer paying any into those premiums.

B (41:38)

The interesting thing, I didn't believe this at 104. It used to be at 104 the life insurance policies became worthless. They now extended that at many companies to 120. I think they're going to need a One of my great friends who runs Western and Southern Life is the CEO for whatever it is, 35 years of Western Southern Life said we should sell more life insurance and less annuities based on this.

A (42:10)

Very much so. Sleep is another one of the ones that they're, you know, there's a, there's seemingly a book every week on why sleep's so important and a lot of people have gotten on it and they wear trackers as far as how they're sleeping and people have made adjustments. Anything new on the sleep front, Mike? Clearly being in a cold, dark place without a lot of noise and getting to bed early and not looking at your device before you go to bed and all those things are, I think, pretty well established now. Anything else that has come out recently that is a hack or a tip that you could give to our listeners?

B (42:47)

No, I think you're set. Sleep hygiene, which is all those areas is key. There continue to be attempts at developing supplement and drug regimens and the one we use commonly is if you're having problems getting to sleep initially it's magnesium and melatonin two hours before bedtime. If you're having trouble getting back to sleep, if you get up to urinate, it is taking those right as you go to sleep and letting those last and melatonin as its side effect. If you get a high quality melatonin and meaning there seems to be some contamination in those made in different countries than the U.S. but if you get the high quality melatonin, then you can go up to 20 milligrams a night with usually without any adverse side effects and maybe with a benefit in the association data, has a decrease in Cancer rates. For people who do that, it may be because they sleep better. But whatever it is, there is a benefit from a higher dose melatonin in the literature.

A (44:07)

As you're talking about melatonin, Mike, it makes me think about supplements and small molecule procedures and things of that nature that you've written about. And then I would add into that peptides, because peptides seems to be the, the topic du jour. Talk for a moment about supplements and peptides.

B (44:26)

We've been our scientific advisory board@4yngevity.com I think it is now 55 supplements and small molecules we've been asked to analyze as routines for people over the age of 50 of that 18 now meet the criteria of having more benefit than risk in a substantial way. So I mentioned two of them. The average person over 50 taking a statin and a GLP one in low dose for both, even if they don't have the risk factors for them otherwise. So we look at it carefully and as I said, I think they're 18. Now some of them are pretty simple and routine. Vitamin D2 with K2, a multivitamin split in half and half in the morning, half in the evening to get a stable level. DHA and EPA, 1100 milligrams a day. So in CoQ10, in addition to the statin, the anti inflammatory statin, if you will, 200 milligrams a day are relatively routine. But there are, as I said, there are 18 that fit into that criterion. Now on peptides, well, the GLP1 is a peptide, insulin is a peptide. So you know, you have to say, how about the experimental or what we say, the peptides that we don't have quite enough data on. And so if you will. That's the problem. We don't have quite enough data. If you look at NAD or resveratrol as examples, both of those, every animal study showed benefit and they have failed every human trial. So humans aren't mice, rats or guinea pigs or even cats or dogs. And consequently we insist on success in the human trials before we would say there's more benefit than risk. So the people who are selling them, we call them wallet biopsy biopsies, that is, they're seeing if your wallet's large enough for them to take a biopsy of it and keep some of it.

A (46:55)

That's great. A wallet by a wallet biopsy. You, you mentioned previously plasma therapy. Talk, talk about plasma. First of all, what does one do when you go and do that? What, what happens in the procedure?

B (47:10)

And let me give you three minutes on the history of it. The history was in the 1930s they one of the major universities was running out of money to support their rat colony. So some investigators last rights to a couple of the rats hooked a old rat and a young rat together in what is called parabiosis. And the old rat got younger. That led to some wealthy guys in the 30s hiring some young boys to give them transfusions. The problem and some of those old guys died because we didn't know enough about blood transfusion, immunology and the ABO subtypes. A lot of that came out in World War II. It fell into disfavor. In the 60s. A group at two graduate students, Irena and Michael Convoy started experiments. They rediscovered it, hooked two mice up and then did experiments with the mice. The old mice ran the mazes faster. The old mice's every tissue looked younger. And then they spent literally 35 years. Other people replicated it. So NIH started funding the studies to say what is it in young blood that makes the old rat Young after 35 years. They then did an experiment where instead of hooking it with young blood, they just replaced it with saline albumin and the persons or the animals old red cells. And it did the same thing. Then they did it in humans. So therapeutic plasma exchange is a FDA approved technology for autoimmune disease. But what it is for therapeutic plasma exchange, you put an IV in one arm that takes the blood out, goes through a centrifuge, cleans it up. You get the red cells, white cells and platelets back in the other arm, plus albumin and saline. In the ambar studies, because the animals ran the mazes better, in 2015 or so, they started a randomized control trial, large scale trial, incredibly well done. And with people with early Alzheimer's, it reversed it. The monoclonal antibodies between 12 and 22% effect. The therapeutic plasma exchange, 71% effect. In this randomized controlled trial. How good was it? Well, they put the IVs in the placebo group too. And then they wrapped it with aluminum foil, ran it behind a curtain and ran the machine so perfectly done placebo group. The placebo group unfortunately continued to deteriorate. That's now been repeated in an Argentinian study. Not as well done the people with their own controls, but every one of the nine characteristics of cognitive function improved. So now as of yesterday, there is a test that predicts when and if you'll get Alzheimer's disease. It's this. It just came out out of the large group on biomarkers for Alzheimer's, you don't have to do a PET scan, you don't have to do spinal tap blood test can predict within four years of when you'll develop it. And with that four year time frame you can say, well, I'm going to get therapeutic plasma exchange in this field or just I'm going to get younger therapeutic plasma exchange in the aging studies done at the Buck Institute. Still with the convoys. The convoys are 80, I think, still working. Irina and Michael and they keep ones that at Stanford, ones that you see Berkeley, they're wonderful researchers and they combined with the Buck Institute to look at this as aging biomarkers. And it reversed or it made the humans biomarkers about 2.6 years younger on average between 1 year older and 3.6 years younger. The muscle biopsies done in 8 of the people look about 8 years younger. So you can tell that the tissue by the density of energy producing organelles and the garbage organelles that are in the cell and you get fewer of those after you go through this. So looks like it reverses aging as well as long Covid as well as the dementia and you know, virtually no side effects. Yeah, you can get an infection anytime. IVs are placed, et cetera.

A (51:50)

And do you need to have any conditions to go get it or could I go get a therapeutic plasma exchange tomorrow?

B (51:57)

You know the I, I invested in this company so that does it. When I read the I'll tell you what happened. I read the study in it came out in abstract form. In 2019, I had a patient who literally couldn't say two words together. Early Alzheimer's. I tried. I called the guy at the Cleveland Clinic. It was done. Two centers at two centers in Spain, two in Chile, six in the United States. Cleveland Clinic was one of them. I called the around our head of our brain says, I don't know, I don't think we're doing this. I called, if you will, the three brain centers at the Cleveland Clinic. None of them thought it was doing it. I finally called the PR agent for the brain center. Each of the institutes of the Cleveland Clinic is big enough it had a PR agent. I called him and after a week he found out that it was Babak Tusi. I called Babaka. He said, I said, will you do this? He said, no, I'm not doing it anymore. I moved on to monoclonal antibodies. And so I called the Mayo Clinic, I called the University of Pittsburgh. Nobody was do it for this indication. So I helped start a company if you will called lifespan-edge.com that does this and in fact confession. I've just had my fourth treatment myself. Not, not because I have any, not because I have any risk factors but because it also decreases the biomarkers of aging.

A (53:23)

You may have a, you may have a new patient very soon. Let's, let's touch on exercise because you're both very dedicated to it and you mentioned previously Mike, about jumping. One of the other things I took from Atiya's book Outlived was the farmer's walk and that if you can carry your weight at 70 years old in a farmer's walk of two dumbbells that equal your weight, that that is a marker of longevity is like an incredible early indicator if you will of being able to live a long and healthy life. It makes perfect sense. Grip strength, being able to lift heavy things, getting in and out of bed, getting up and down stairs, all that kind of stuff all, all correlates well. Anything new on the exercise front mic beyond the three days a week that you mentioned previously, the jumping that you've mentioned I just mentioned the farmer's walk is being a really good indicator of longevity when you cross the 70 year old threshold. Anything else?

B (54:33)

No, I think a lot of it is data. The best data we have is from the Harvard and the Penn Alumni studies And there are three components that make a difference plus jumping. So fourth component is jumping. They are any which is 10,000 steps a day still is in the, in the 23 studies that have been done it's still 10,000 steps a day for less disability and the least all cause mortality. It is 21 minutes three times a week of cardio at 80 plus percent of your age adjusted maximum heart rate age adjusted max is 220 minus your age times 80% is what you want to do it. And then the new data is the last two minutes you really want to go all out and see if you can get to 100%. It's called high intensity interval training in that last two minutes of the 21 minutes and then it is resistance exercise. The easy way of doing that if you want is every even day of the month. You get an extra day off at the end of the month but it is, it is literally those three plus 20 jumps morning and night on a hard surface.

A (55:49)

And Mike, do you track your VO2 max?

B (55:53)

You know I, I do it every couple of years so I don't track it routinely. But you know mine this is ridiculous. My I'm 80 and it's 55, you know, so, so, you know, I, you know, I have no idea why it has been that way, whether it's because I've kept the training up or whether it's my genes allowed me to keep the training and keep it there. But it's ridiculous. It's a very high number for someone my age.

A (56:24)

It's an extremely high number for someone your age. Does that, do you think that, that. Are you pretty consistent as it relates to that max effort at the end of your cardio exercises to try and keep that up there? Because one of the, one of the big differentiators on maintaining VO2 max to my understanding of it, is getting on a stationary bike for half an hour, 40 minutes is great and good and very helpful for both controlling weight and just getting your cardiovascular system running. But it doesn't help you much on that VO2 max unless you're pushing yourself to the extreme.

B (56:59)

I push myself to the extreme three times a week. My last two minutes of, you know, I, whether it's a Schwinn bike or a elliptical or a rowing machine, the last two minutes. And I try and alternate a little bit and have, have a little gym at home and a little gym in a second home. And so I don't go anyplace, I won't go to a hotel without a gym. And so routinely I will do the last two minutes as high as I can. And I can tell you after I got repair of my shoulder, I did something you should never do, and I can tell that is don't skip the warm up. So I was late, I didn't have enough time. So I did press, bench press without the warm up, and I tore my rotator cuff. Then I took six weeks, six if you will. It was six months of rehab and I wasn't able to do the hit during that time. And so I, my heart rate went from a max of about 170, 72. This is just a few years ago. So it's still when I was in the 70s down to about 148. And I've gradually built it up to 166. So I'm, I'm still over, you know, if you will, at 80, it should be 1 140. Right. But I can get it up to 166. So.

A (58:36)

And where's your resting heart rate these days?

B (58:39)

Oh, it's about 46. Yeah, yeah. But anyway, but so it doesn't surprise me. So I'm a true believer in exercise for stress relief and as well as for maintaining your rate. Of aging. The data are pretty good. You know, stress management is number one, nutrition is two, and physical activity is three for those without chronic disease.

A (59:09)

Yet I got in a I went to the airport this morning with two colleagues of mine in New York, and they came to pick me up at my hotel. And I stay at the Equinox Hotel on the west side in, in Hudson Yards. And one of my colleagues said, why do you stay over here? Because our office is in midtown at one Vanderbilt. And I said, it's real, real simple. It's got an incredible Equinox gym on the fourth floor, and that's very important to me. Second of all, they have blackout shades in every room. And so I get a good night's sleep because of the blackout shades. The rooms are built like fortresses, so you don't hear anybody in a room next to you. And they have thermostats that allow you to control the temperature instantaneously, where you can take it from 72 of sort of living temperature to 68 for sleep temperature, and off you go to sleep. And my friend turned to me and he goes, that's the most concise kind of reasoning I've ever heard on why you'd stay at a hotel. And I said, you know, that's the, that's their model. And I said, other, other hotels have a great lobby bar where you hang out and see lots of people and have a good drink. And that's just not what I'm looking for in a hotel. But next time you and I are in New York together, maybe I'll get you to come stay at the Equinox with me.

B (60:16)

Sounds like very good plan.

A (60:18)

Thank you, Mike. It's always great to see you. Your insights on longevity and health and all that are just, they're so practical. They're so real. They're so grounded in research, they're so grounded in your own life and your own experience. And I'm just deeply thankful that you came back on again. And I look forward to our next conversation when you've got new research and new ideas to share with everybody.

B (60:45)

Within five years, we're going to know whether you and I can be 40 again.

A (60:53)

I, I look forward to it. Something tells me you're going to beat me on that race. But I, I, I'd love to be in the race with you, Mike. I. Have a great day. I'll say hi to Peter for you tomorrow and have a great one. Really appreciate you spending the time.

B (61:06)

My privilege. Thank you very much. Sa.