 So, welcome everybody. It's really my great pleasure to talk to Dr. Walter Longo, who has recently published a book, The Longevity Diet. And it's a pleasure of mine because I've been a big fan of his research and you've probably read in the Plant Paradox that I definitely reference your work. And so, it's great to have you here. So, what compelled you to write The Longevity Diet? The Longevity Diet is really the result of 25 years of work, starting back in the days with Roy Wolford, who was my mentor. It was at the time, I think, the leading figure in the world for nutrition and longevity. And he has written some books on the topic, of course. And I just thought that it was 25 years went by. And at that time, there was really not much genetics available. We didn't know what genes controlled aging, what genes prevented diseases. And certainly, the calorie restriction, which was the intervention that he was really promoting, which is the chronic reduction of calories, did work very well. It taught us incredible, it gave us incredible findings. But at the same time, it just showed us, this is probably not the way to do it. You know, people are not gonna be willing to do it. And even the monkeys did not live that much longer. So, there was time to really do it differently. And I think that the longevity diet, I waited until I finished clinical trials. And then I felt, okay, now we can go out and tell people to do something there. It's been clinically tested in randomized trials and it's safe. Of course, you can always do additional studies. But I felt that it was enough to really make a difference. Yeah, so what, you know, you and I think probably long-term calorie restriction is not the way to go. And, you know, I've read all of your mentors work a long time ago and it was actually influenced a lot of my work. But I agree with you that, you know, long-term calorie restriction, it's not the answer. Most people won't do it. And certainly it, in a way, didn't work out for Dr. Wolford in the way he thought it would. But there's lots of mitigating circumstances. So give us a little bit of the background of your studies, first in mice and in people that kind of led you to your current thinking. Yeah, so the original studies were mostly genetics. And so the first was the identification of the TOR, a cis-canase signaling pathway and showing that if you mutated that, that you would get extraordinary effects on lifespan and also on protection. Then we went on to show, this was what we called the protein ageing pathway. So response to high levels of amino acids and proteins. And then we identified the PKI, RASPKI in yeast and PKI probably only in mammals, the response to sugar. So if you have lots of sugar, these genes are turned on. And so we think that the protein pathway and the sugar pathway together, they're really pushing systems to age more quickly. And the master regulator, or one of the master regulators in mammals and humans, we think is the growth hormone receptor axis, meaning that the set of genes that are controlled by growth hormone. And eventually we were able to start studying this population in Ecuador that is lacking the growth hormone receptor. So they're about three and a half feet tall. And just like mice that lack the same receptor are long lived, protected from cancer, protected from diabetes, and protected from age-dependent cognitive decline. We show that these people probably are just a little bit longer lived, not big effects, but very much protected from cancer, from diabetes. And the latest paper we show with you doing fMRIs here in Los Angeles that they seem to be protected. They seem to have a younger cognitive profile. So the type of learning and memory abilities that you see in somebody that is younger. Yeah, that's fantastic. Yeah, I got interested in TOR many years ago as a transplant immunologist and surgeon. And we were actually researching Rapa Mycin. And became fascinated back in those days, you had actually had to have animal studies that showed how lethal it was. And lo and behold, everybody's surprised. Rapa Mycin, given in the proper doses, these animals were living an incredibly long time. So that's my background in that. But we both really kind of focus on two things that the average person can take home with them. And that is that sugars are bad for the aging pathway. And unfortunately, certain amino acids that are more prevalent in animal protein than they are in plant proteins. This is kind of the one to punch. And I grew up in Omaha, Nebraska, in the center of the United States and a meat capital of, you know, of America. And so when people say, Well, gosh, you know, I really don't want to give up my meats and animal proteins. And I really don't want to give up my sugars. Can you can you say why you think both of those things are probably equal and equal in importance in producing longevity? In accelerating aging. I probably think that it has to do with reproduction and growth, right? So to grow, you need fairly high levels of both. And to reproduce, you need high levels of both. And you cannot have a baby would make any sense to have a baby if you did not have sufficient. Also, because evolutionarily, that would be an enormous investment of energy wasted. So I think that's probably where the all of this comes from. You need enough protein, enough protein reserves, enough sugar, enough sugar reserves, and to to face, you know, the nine months to to have a baby. But of course, you do it in the sacrifice, not of course, but probably because there is just not enough energy to go around for everything. And also wouldn't make sense that you have put so much energy into not aging at all. There is probably no benefit of keeping somebody not aging, or at least we haven't gotten there yet. And so I think it makes perfect sense that now you sacrifice repair and protection for the sake of growth and reproduction. And this is pretty consistent in many different organisms. And I think it's a pretty good, it's very clear, you know, in a cell, we've done a lot of work, for example, with chemotherapy resistance. And you see very clearly, if you push the cell, if you starve a system, you reduce the glucose in the protein, it becomes protected, but it doesn't divide, it sits there, it becomes smaller, usually in size, and it doesn't divide. As soon as you give the amino acids and the sugar, it becomes larger, and it starts dividing, and it can divide very rapidly like cancer cells. But when they divide very rapidly, they're very much unprotected, very sensitive. Yeah, so that brings us actually to a good point. You and I are both fans of fasting. I know you and Joseph McCola have talked about this. I think he's probably more on the Jason Fung side of things, that a four or five day water fast is a great idea, maybe once a month. You on the other hand have the fasting mimicking diet. So could you kind of talk about the benefits, the drawbacks of both of these systems? Well, we started with the water only fasting and we started with cancer patients 10 years ago or more. And I have to say it was a disaster. It was a disaster for compliance. It was a disaster for potential safety issues. And it was a disaster also, or certainly problematic for doctors compliant. So doctors really felt that they were exposed and they were doing something they didn't feel comfortable with. And so did the patients. So this is how we started. And then we went to the National Cancer Institute and basically say, this is a problem we have. What about a diet that mimics fasting? And I mean, I think I speak from experience having done this for so long and really talk to thousands and thousands of people and hundreds of doctors. The water only fasting seems like a good idea because it's free and you feel like, oh, I want to give it for free to everybody. But when we did that in Europe, for example, it was also a disaster when people were allowed to improvise the fasting mimicking diet because people go home and do all kinds of wrong things. People are not pharmacists. They're not trained to make their own drugs or medical food. And of course, whereas, let's say, take 100 people, maybe 90 will be fine at any given cycle. And so if you look at it from 30,000 feet, you think, wow, no big deal. But if you really get down there, you realize how a lot of people will have problems with the water only fasting and a lot of problems even would improvise diets. And so I basically gave up all the financial benefits from the diet. I don't make a penny out of any of it and never will. But I felt and it was the right call, do something that you clinically tested in patients that doctor that's always the same. Now it's over 25,000 people have done it with thousands of doctors. And it was tested in randomized clinical trial. So we really feel very, very positive about the safety. And also I have to say a lot of the funds eventually will go back to research and universities and institutions. So even, you know, buying the kid is really benefiting the research. And it's a good cause. And I think, yeah, for all those reasons, now, we're only fasting can be done in a clinic, in a specialized clinic, you know, so the true North, for example, in Northern California does that. Absolutely. And the Bookinger Clinic will help me clinic in Germany is another good one. And so if somebody can can go to these clinics and by all means that they've shown a lot of very good effects. Now, when it comes to disease prevention, disease treatment, et cetera, then you have to prove it. And even in those cases, the clinical trials have been very few for those diets that we're doing, many with the FMD. And so I think, you know, everybody else got to just do clinical trials and show the results, both mouse work and clinical trial. And then I think it's ready for recommendation. So for the purpose of people who either haven't read your book yet, or haven't read deeply into the plant paradox, can you can you give us a nutshell of what the fasting mimicking diet does and why you think and quite frankly, I think that this is a really good way to go about things. Yes. So the main thing mechanistically, I think if you look at our works is the breaking down. I like the analogy of a wood burning train all that cannot does not have enough fuel to make it to the next train station. So it starts burning the damaged chairs, the damaged walls, and then makes it to the train station. And then of course, it's lighter and it can make it there. And now it can rebuild, right? It can rebuild the chairs, rebuild the walls. So now you have a, you know, not a completely new train, but certainly a train with new chairs and new newer walls. And that's what the body does. And now we after many papers, we have a pretty good idea that this is very consistent. So whether it's the liver, the pancreas, the hematopoietic system, the blood system, the nervous system, and probably the muscles, probably everywhere, the fasting shrinks system because it's trying to get lighter. And it's trying to use either intracellularly by autophagy, or cellularly by just destroying cells and saying, I don't need, for example, why blood cells go down, or you don't need, if you're starving, you don't need all the white blood cells that you normally have. So you slowly get rid of some and you don't need all the muscle that you normally, so day by day, some of the muscle is going to be utilized for fuel. And then in that moment, what we discovered a few years ago was the stem cells are getting activated and the cell is getting ready also to rebuild. So now in the refitting moment is when most of the incredible programs occur and you see embryonic and developmental genes that are being expressed at fairly high level, genes like nano, and probably even of four, although it's been a little bit trickier. So some of the genes are involved in pluripotency, the stem cell ability to make almost anything. And you see them turned down at a very high level. So in that moment, then you refeed, you have the amino acid. So the same things that are best for you before now become essential for you to rebuild IGF-1, Tor, and PKI, et cetera. And then you rebuild. And that's what I think is really the foundation for a lot of the positive effects. So, and I think the interesting thing that you've shown is that this is something that you don't have to do a modified fast for every day of the month. You've found that, in fact, that people can do this for five days a month or seven days a month and eat normally the rest of the month and act as if they had been restricting calories every day. Is that putting it safely? Yes. So what we've been saying, what we've been seeing is that the, first of all, the diet works by far much, much better in subjects that have lots of problems. So if you have high cholesterol, high blood pressure, high triglyceride, fasting glucose, and you're pre-diabetic, that's when it works the best. And then in the clinical trial, the people return to the normal diet. And what we saw was that many of the effects were long lived. And so the five day restriction seems to reprogram so what, for example, IGF one, if you look at one week later after the third cycle of the fasting vegan diet, and then you even look at three months later, you still see the IGF one being much lower in the people that started with very high IGF one. Now the people started with normal IGF one, it comes down a little bit and not so much long term. And so of course, this is very good news because whereas calorie restriction, chronic calorie restriction drops everything gradually, including the muscle, the IGF one, the blood pressure, so it keeps coming down. If you look at the biosphere too, when my boss Roy Walford was there, after a few months, their blood pressure reached, they started with 110. They were very healthy. And then it reached 85. It was like 85 or 55. So the blood pressure keeps dropping. In our case, we don't see that. So if you have a high blood pressure, you go back to normal. If you have a low blood pressure, you stay there. That's really interesting because it tells you there's probably fixing problems rather than just blocking pathways that are involved in blood pressure maintenance or glycemic levels. Fantastic. So one of the things that you write about in the book is that you spend summers visiting, you know, one of the oldest living villages in Italy. And what, what have you learned by observing these people? And the second part of that is, how do you compare this village to the other blue zones? So maybe one at a time? Yes. So the, the time, I mean, Italy, Calabria is one of the villages we spend a lot of time with. And the other one is Sardinia now spending more time with Johnny Pass and others in Seulo and Villa Grande. There are these very record world record towns in Sardinia. And of course, I know I visited Craig Wilcox in Okinawa several times. And I visited the people in Loma Linda several times. And I think it's just surprising how similar every play everybody has their own version of this vegan slash some plus some fish or sometimes plus some meat, but very little. And most of them seem to have this in common. Now, an interesting thing in Malocchio in Calabria, where I really grew up was that, you know, we published a paper a few years ago showing that if you, if you look at up to age 65, low protein diet is associated with reduced risk for cancer, reduced the risk for overall mortality. But after age 65, that's all that turned around, right? And so I started thinking, it couldn't be that these people, whether they're in Okinawa, Loma Linda, or Calabria, Sardinia, they're doing the same. And it turns out, we think it's a little bit of speculation, but it's very clear what it's happening. They a lot, lots of times they either go to a nursing home, let's say Loma Linda, or they go live with their sons and daughters in Calabria, or Sardinia, and they start eating a lot more, right? So, so we we think that because of this somewhat of a coincidence, right, they do the exact the optimal phase specific diet. So they, they under eat out to age 70, 75. And then they slowly start eating better, more maybe they eat some meat, etc. So, so we start, I mean, at least the evidence is now suggesting that maybe that's the best way to go. For example, IGF one is very high up to age 45, 50, 60 even. And then it drops down dramatically in somebody who's 85. And so we saw, for example, that people had low protein diets and people that high protein diet when they were age 65 did not have any difference in IGF one. So this will be consistent with the idea that you may not need anymore to be restricted that much. And in fact, you might need to do the opposite once you get to age 65. And that's exactly what you see in almost all these groups, not all of them, but many of these very long live groups tend to have these two phases of life where they, they now start eating more at a certain age, just because they're in a place that sort of forces them to eat more. Yeah. And have you had any chance to look at the folks in South and Naples and at Chirole? Yeah, I went there. I went there a few months ago, I spent a few days talking to the dieticians and the scientists there. They're there, you know, in many different places, the data is still not very well developed. So I think they need to do more work. In, in trying to figure out, you know, how many, there's certainly a lot of centenarians in the Chilento area, and they seem to be at a prevalence that is higher or much higher than many other areas. It's not as high as it's a little town, but it makes sense. Chilento is a large area. So I think, you know, there's several scientists that are doing work there. And it's bound to, they're bound to come up with some very interesting, very, very interesting findings. You know, and again, the diet is the same, you know, when I interviewed many of the centenarians, you keep hearing the same story. Some fish, not very much, and lots of vegetables that could get in the back yard. And, and sometimes they would maybe use meat to make minestrone type, you know, vegetable type soups tastier. And differently from what people think, these people did not have huge dishes of pasta and, and, you know, bread. They had some pasta, but even pasta, when you ask them, say, there was expensive, you know, so we read that I put green beans and, you know, and all kinds of other vegetables, and then put a little pasta to make it taste good. But we did not want to do what now everybody in the world does. And it's extremely damaging is to have these 120 grams of starch and, and, and nothing else. Yeah, I was very impressed. They really, I found the same thing. They, they didn't really have pastas and breads like other parts of Italy. I was also impressed with their use of rosemary, which has fascinated me as a, as really an anti-aging brain protective compound. So, well, that's great to hear. So we're kind of running out of time. What are you working on now and where do you see the future of longevity research going? Well, so now we're doing a lot of work. I mean, many more diseases. And, and so we just published a paper on pancreas damage, we damaged the pancreas of mice. And then we did the fast-making diet and we showed that we could reverse the, the lack of insulin production. So essentially reverse both type one and type two diabetes in mice. So now we did the same for, for multiple sclerosis in mice, mouse models. And, and we started, we have some data on the people but clinical trials. But now we're, we're really systematically going through many clinical trials. We have received funding for type two diabetes now, received funding for Alzheimer. We have about five trials for cancer ongoing right now. And, and so we're going to do a large one with metabolic syndrome. Yeah. So I think in the next couple of years, we're probably going to have five, six, seven clinical trials published on the use of the fast-making diet. But not always the same. Some of them are lower calories, some of them are longer, higher calories, some of them are longer, less than a week. For example, for auto-immunities, we're going to test a fast-making diet that are a week long just to get more effects on auto-immune cells, have more killing of auto-immune cells and more activation of stem cells. So yeah, those, these are some of the things that we're going to be doing in the next few years. Alright, great. Well that's been fantastic. And, you know, keep up the good work. Like I say, I've followed you through the years. I followed your mentor. And we should stay in touch because I love what you're doing. And thanks, thanks for spending time with me today. Yeah, thank you. And thanks for the great book you wrote. And, and folks, get Dr. Longo's The Longevity Diet. You can, I'm sure, find it at Amazon, Barnes & Noble, or your local bookstore. It's a very good read. And he's, he's truly one of the great experts on longevity there is. So listen to this guy, okay?