What If Aging Is Mostly Inflammation

A plastic surgeon spends decades helping people look younger, then a heart defect, major valve surgery, and a type 2 diabetes diagnosis force a deeper question: what actually keeps us younger on the inside? That’s where Jim’s story gets compelling, because it’s not built on trends. It’s built on lived experience with cardiovascular risk, atherosclerosis, and the kind of motivation that makes longevity science feel urgent and personal. 

We walk through the research that pulled him into calorie restriction and intermittent fasting, including alternate day fasting and why timing and metabolic markers like insulin and glucose can matter as much as the scale. Then we get practical about what fasting is doing at a cellular level: lowering systemic inflammation, pushing back on “inflammaging,” and supporting autophagy, the cleanup process that helps cells recycle damaged components. If fasting sounds too simple to be real, the biomarker results and clinical observations we discuss will challenge that reflex. 

We also talk supplements through a longevity lens, not as magic, but as supporting players: spermidine for autophagy, senolytics as an emerging area, and natokinase as an intriguing tool in the conversation around plaque biology and cardiovascular health. We wrap with Jim’s work supporting longevity research, plus the release of the film Forever On and where to keep learning. Subscribe, share this with a friend who wants a realistic longevity plan, and leave a review with your biggest question about fasting and healthy aging.

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Transcript

Cold Open And Show Setup

SPEAKER_00 0:00

Your career as a plastic surgeon helping people look younger on the outside there. And at some point you walked away from all of that and actually went into making people younger on the inside, right? So what was that m moment in in your life, in your history there that made you a shift?

SPEAKER_01 0:15

I had a bicuspid aortic valve, which is a common anomaly, crank down to about the size less little less than the the diameter of a dime. And that is what required me to have an operation, so-called Ross procedure. Same operation that Arnold Schwarzenegger had.

SPEAKER_00 0:34

Can you explain a little bit more of what's going on in our bodies when we do fast and why it's so good for you?

SPEAKER_01 0:40

The best new thing that I've heard about in the last year or two is uh natokinase is an enzyme that breaks down fibrinogen, which is an element of plaque. If you you take it on a regular basis, and I'm talking about a thousand milligrams a day, it reduces the plaque burden in your entire body by about thirty-six percent with after a period of eight months, which is a remarkable benefit.

SPEAKER_00 1:09

I love hearing you talk about something such as simple as fasting, or or low cost if nothing else, but also having the the compounded benefits of over time of weight loss eventually and inflammation and and all of that. This is the Longevity Loop Podcast, and I'm your host, Brent Wallace. In every episode, I bring you the leading voices in longevity, plus my own insights, to put the world's best strategies directly into your hands, making elite longevity strategies accessible to everyone regardless of your background. So let's jump into the loop starting right now.

Why He Left Plastic Surgery

SPEAKER_00 1:54

All right, Jim, welcome. You spent your life and career, maybe not your whole life, but your career as a plastic surgeon, you know, helping people look younger on the outside there. And at some point you walked away from all of that and actually went into making people younger on the inside, right? So so what was that moment in in your life, in your history there that made you shift from one thing to another?

SPEAKER_01 2:19

Well, I

Heart Defect And Life Saving Surgery

SPEAKER_01 2:20

think it was actually very early in my career because I had a couple of things, a couple of health issues that made me focus on certain things. Uh when I was 19, I was listening to my own heart and I heard a a diastolic murmur, which nobody had before that heard. I went to the heart station at the University of Michigan, and uh they told me that I had a bicuspid aortic valve, which is a common uh anomaly, is is the most common anomaly. For two of the three valves in the aortic uh valve are sort of fused together, and that causes turbulence in the flow of the blood over that passage. And over time, it causes the deposition of calcium and exaggeration exaggerates the effect on atherosclerosis. So when I was about twenty, I worked for a pathologist, and they would do these autopsies on people that had died suddenly. And my job was to get a slice of the heart because we wanted to look at the degree of ischemia from the center of the event out to the more peripheral parts. And what I was struck by was how the entire aortic uh root, the whole looking at it grossly, was just covered with atherothoratic plaque, yellowish stuff that you know you couldn't really see any of the anatomy. And uh that led me to uh understand that the this process that happens with virtually everybody that has a bicuspid valve, if they the valve is not very deformed, it it takes longer for it to uh become more deformed. What happens is there the deposition of calcium in the atherosclerotic plaque leads to a uh stenosis of the valve. So if your your outlet normally is, say, the size of a quarter, a little bigger or smaller, nine over a period of about 30 years shrank down to about the size less little less than the diameter of a dime. And that is what uh required me to have a an operation, so-called Ross procedure, same operation that Arnold Schwarzenegger had. Uh, in his case, they accidentally cut into the one of the pulmonic valve leaflets. The procedure is to take the pulmonic valve, which is a three a three uh leaflet valve, put it in the aortic site, and it can it can tolerate the the cystenite pressure, which is you know 120 over 80. And then in the pulmonic site, they put in a homograph from a cadaver that has been purified. And uh that whole period of time, when from I when I first found out what I had, and I noticed that I saw the atherosclerosis and the calcium, I was concerned about it, and I took various measures. For example, taking aspirin in high doses, which I think did slow down the process. And it was a concern all my life. I mean, when I went to the heart station, uh Park Willis was uh the uh physician in charge, and he he told me I shouldn't do anything like uh it was in Michigan and and pushing a a car out of the snow if it was stuck, or playing basketball for an hour because of the stress on my heart. Now that's no longer a belief, but it it affected me in various ways, I mean, psychologically and thinking about these things. And it turns out that a lot of people who are interested in age science are have some kind of a history like that. So I had one uh when I was 56, I had this procedure. I went to Oklahoma to have the the guy that had done the most procedures do it, and that that's a big operation where they take out the aortic valve and take out the pulmonic valve and put it over here and then put this valve back. And then in addition, I also had an aneurysm, six six centimeter diameter aneurysm of my aorta. They had to replace that. So it was a it's a big procedure, and a lot a lot of most cardiac surgeons had have never done the procedure, and I think it takes uh somebody with extraordinary talent and can do it fast, because you're uh you have to be on a coronary bypass, pulmonary pump, you know, for some length of time. And I I was on it for two hours and ten minutes, I think, which is pretty pretty lengthy. But I, you know, I I did fine. I've never had any problem with it. Unfortunately, Arnold had one of these valve leaflets that uh they cut into accidentally when they were taking out the pulmonic valve, and this is common knowledge, I guess. And they sewed it up, sewed up the leaflet, and went ahead and did the procedure. But the next overnight it became apparent that he had a complete insufficiency, meaning the the blood was being pumped through the from it's from the heart into the aorta, and then it would come back in. All the all the blood would come back in, and they had to take him back and do a replacement again, which was I think they used a pig valve, which is used for a long time. I they probably still are, but it was it was a uh it just shows to me the the complexity of the procedure, and I'm extremely grateful that these these people were so skilled. And uh Fray Elkins is now the the son of the guy who originated the procedure in the United States, and he's he's he's moved on to doing nothing but heart transplants. Um that was in 2003 when I had the surgery. But the the whole experience made me acutely aware of what what things can happen and the nature of atherosclerosis and all kinds of things. So and then I became diabetic when I was 44, I guess, or 46. Type 2. My parents both became type 2 diabetics, but at a and a later age. So but I had the genetic predisposition. And those two things certainly made me much more conscious of uh what it takes to survive.

Diabetes And The Longevity Wake Up

SPEAKER_01 8:39

And uh I just was extremely grateful that I could have the kind of medical care that I had by these really expert surgeons and and the uh treatment of diabetes also. So I was practicing plastic surgery, but I became interested in lots of topics related to longevity, especially calorie restriction, because Roy Walford was the scientist at UCLA who did a lot of work on calorie restriction. And uh he he uh was a I I read what his work was about, but I I got to the point where I was uh I was still practicing, but I became interested in what what was in the uh the science going on regarding calorie restriction, because it's such a a powerful force for good health. If you can get people to follow a a calorie restriction plan, by calorie restriction we mean giving an animal less than it would normally eat to maintain its weight. If you re restrict the can the animal by 40% of its calories, that is, to a 60% level, they will live 40% longer, which is a striking fact. And then uh in 2003, Mark Matson of the National Institutes of Health, who is the the uh theorist behind all the calorie restriction forms that humans have adopted, that is intermittent fasting, wrote a paper in which he showed that a fat mouse could be healthier than a thin mouse if it was fed every other day, which didn't make any sense to me. But the the the the fat mouse was modified genetically so that it ate most of the food on one day, and they they studied it and showed that it's uh it's uh the level of insulin and glucose in that fat mouse was lower than it was in a calorie-restricted mouse, which is very significant because those two biomarkers are very significant. And so it it it was sort of like an epiphany for me to hear this because it was it went against all the information we have about obesity. And so I decided to try something like what he was doing, and I uh figured I could probably get by on 20% of my normal calories, because if you have a hundred percent one day and the next day you have twenty percent, those two days 120%. If you divide that in half, that's 60%, which is a level that imparts these really miraculous kinds of uh defensive mechanisms against uh aging process. And I had my patients start doing it and friends and people thought I was nuts at the time. And uh but I I organized a trial. I I wanted to show that it had strong anti-inflammatory characteristics, and uh so I chose to use asthmatics who had who were obese. And because I I didn't think that I could recruit people simply on the basis of wanting to go on a diet, and I did recruit uh, you know, the sufficient number to do the study I did, and it I got one of the the pulmonologists at LHU, head of the department, and uh we did the study, it was eight weeks in length, and it showed remarkable changes in the all the various biomarkers by reducing markers of inflammation. I went to a meeting of the Calorie Restriction Society where it happened coincidentally that Mark Mattson was speaking. He was a paid speaker, and I introduced myself and he became very interested in it because nobody had done any any trials like this. And he said, Do you have frozen samples? And I said, Yes, 180 of them. He said, Why don't you send them to us? So he and six postdocs worked on these things to analyze things that you couldn't get done anyplace except you know the NIH. And the results were striking and remarkable. The the level of one thing that is a part but related to oxidative stress, a uh molecule called nitrotyrosine, and has been shown to be the most accurate predictor of uh a future heart attack. And it went in three weeks it went from the the initial level down ninety percent. And there's never been any study that showed that degree of change. Then other markers like TNF alpha, which is the primary source of inflammation and rheumatoid arthritis and other things, went down by 70 percent. These are very striking changes. And so we published it, and uh it uh there thereafter, this is in 2004, a long time before anybody really caught on to it otherwise, then other researchers did catch on, and uh they have done a lot of work that's very uh explicative of what the various processes going on are, the molecular mechanisms, the downstream effect of calorie restriction. And I I had I was satisfied at that point in doing that because I it it I had exploited this this this process, the calorie restriction mechanism, which has been in living creatures for three billion years, all creatures. And uh I didn't I did I wrote a couple of other minor papers, but it it was I I decided it was not sufficient interest thereafter to do a study because the one I did was so all-encompassing, I mean, in my life. And I was still practicing plastic surgery, and I had I paid for everything to get the assays done. I went uh my uh vacation home to the polynologist to get him interested in doing the the work that had to be done with the with regard to the asthma. And it was, you know, a thrilling thing, but it it it it takes the you know, you see studies in journals and uh you think, well that's not that can't be very much work or something, but it it is it's not true. They're they're prolonged processes and they're they're difficult to get done, and it's uh and I I just decided that I I was did not want to be a diet doctor anyway. So I kind of uh stepped back from that. But I the I wrote a book called The Alternate Day Diet with my colleague Don Lau and uh at times there were some of these sites on the internet, like I think low carb something or other, had people 250,000 people followed my diet uh for periods of time. And so I had this strong interest because i i I used it myself.

Fasting Approaches And Early Backlash

SPEAKER_01 15:44

I still do, I still do fast, not in such a formal fashion, that is every other day doing 20%, but uh I'm always fasting either in the in the manner that uh Mark Mattson favored thereafter, which was not eating for twelve hours or something like that. And so that's that's probably become the most popular form of intermittent fasting. But I wrote the first paper that was on alternate day fasting, which was really the the original intermittent fasting paper.

SPEAKER_00 16:18

Yeah, there's so many I I feel like there's so many different ways that fasting can be, you know, achieved there. Like you had the alternate day fasting there, and then I feel like one of the real popular ones now is the 16-8, you know, like sixteen is not eating and then eight hours, and then which, you know, some people can stick to, and then I I feel like Brian Johnson kind of came along and started doing the more fasting towards the end of the day instead of the beginning of the day, which I feel like a lot of people do, you know. So I don't know what your thoughts are on just like the different timings of it, uh or just maybe it's I think it is all good for you.

SPEAKER_01 16:51

And I think Walter Longo is probably the thief uh guru in terms of uh fasting now because he demonstrated that uh if you fast for three days or four, I think maybe, that it uh renews your uh your immune system, which is for people my age, as you get older, get past fifty, is a very significant concern. And I was gonna actually do a study with him, but then I thought, no, it's I I I I didn't I didn't have the the motivation because it was they're so they're so all in enveloping, you know. They're these studies are are a major part of your life. And uh so I didn't do any more after that. Uh but uh the book came out in 2008. I was on uh national TV. I'm still on you can still find me on the internet, and uh I was on Fox News and that Dr. on their Siegel was the opposing view that they have, you know. And uh he basically said this is nonsense. And I said, no, it's there's an abundance of evidence for this to be exactly as I'm saying. And of course, as time went by, it became obvious that it was a very valuable thing for human health. And Mark Matson has written several articles since then saying that part of what you do uh if you want to age slower and be in better health is some kind of fasting, intermittent fasting or the 68 or what whatever. It and it it it's it's very difficult to um you know exclude all the variables that are involved. So I can't say that one works better than the other, but I know that our original study, which is still the most cited on alternate day fasting, had findings that were I've never seen anything duplicated. And uh so it's I when I when I re when I retired, I moved to Marin County, California, and the Buck Institute is about 15 minutes from my home, and I was very interested in research, and I went there and I gave some money to a couple of people for specific projects that they were working on. And uh they then uh asked me if I'd want to work on a a study of uh ketone esters, which I did, and uh they demonstrated, you know, that in older patients that is, trying to try to re repeat or reduplicate what the have the studies that have been done in young people. And uh there's they're still continuing to do it. It was the first clinical trial at the Buck Institute, and they they uh that's the bike trial, yeah. Bike bike trial, yeah.

SPEAKER_00 19:43

Yep.

SPEAKER_01 19:44

And uh so since then I've uh branched out and I've given them substantial amount of money and various studies that that interested me, but it was it's it's very nice because I can talk to them as a clinician. I'm not I'm not a bench researcher, but I like the relationship because I'm working now with uh a neuroscientist, uh Lisa Ellerby, and Birgit Schilling on a a s a study that's gonna be very interesting, and we're gonna re uh relating the the bone to the brain, and we may have some information that would uh change the way in which Alzheimer's disease is is uh treated. Wow. So that's very exciting to me. Yeah.

SPEAKER_00 20:26

Yeah, that's awesome.

SPEAKER_01 20:28

But uh uh I met David uh Dolly, he was uh he came through to uh interview I think Eric Verdon and maybe somebody else at the buck. Eric Verdon is the CEO, and he interviewed me because I was the spokesmodel for the the uh Tetone Esther study and and he videoed me and knew who I was, and then a couple months later he got them to call me to see if I was interested in being involved in a film that he was making. And I said I was interested, but I wasn't gonna give me any money, but that soon changed. And I and I and I I sponsored basically the entire film that we have made, which has turned out to be uh uh an absolute delight in in my life and the others because it's it's such a good film, and uh, you know, it's it's exciting to see something like this happen.

SPEAKER_00 21:26

Yeah, yeah, that film is is amazing. When I was talking to David, he let me watch uh the movie uh this pre-lear release, and I got to see it, and yeah, it it's really cool. And I love how you are featured, you know, just all throughout it, you know, like the opening scenes of you working out, and then you know, towards the later scenes of you know, like we mentioned right before we started hitting record here, he's like you playing music on your Stratocaster, and I'm like, All right, this is this is pretty cool stuff here. So just to drop a quick plug for I I think it's coming out this month or is I think it's June today. Today today. Oh, amazing. On Apple TV. So I know it's available for pre-order, so people can actually watch it today on Apple TV. And it's titled Forever On.

SPEAKER_01 22:12

If you just go to your TV and turn on. If you have Apple TV, you can watch it right now. Yeah, that's so cool. And then we just found out we're going to be on Amazon and uh YouTube and probably a couple of other streamers. So that's so cool. It should be available to you know anybody that wants to see it.

SPEAKER_00 22:32

Yeah, yeah. And I highly rec recommend it. I mean, I always geek out on the longevity films. Uh you know, the the there's a few of them out there that I really enjoyed, but I really enjoyed this version because it really and I feel like a lot of these types of documentaries based around aging and longevity are all gonna have this element of the future in them now, you know, and that's what's really cool about this film, the Forever Young film that you uh were in, is just I just love the technology aspect of it. Talked about like, you know, toilets is gonna are gonna like after you, you know, take a bio break and it's gonna be like, hey, you know, you got this going on, or you know, just like your personal assistant is gonna be sitting on the countertop with you and say, hey, these are the vitamins you should take today and custom formulate. And it's just I'm really excited for that type of future, you know, where we're just like, you know, it takes the all the things of the wearables that you know we wear and all the data that we have, but actually turn it into actionable things. And so yeah, that's what the film the film is so cool.

SPEAKER_01 23:30

It the the my motivation was that I had been doing philanthropic things there for several years. And uh when he c came through and he said he was gonna make this film, I thought this this is what I want to do for the buck because it'll raise their profile, and we could make a very very good film that was not uh biased in any way that we could avoid it, and uh that it would uh be interesting to people because it would not be all science, but uh some of the humanistic emotional aspects of what we all face in life and what what our decisions are gonna be when the choices e exist to live longer and many different uh sort of existential musings, as as you saw. And my daughter was in it, she stands out, I think, in it uh she's a psychiatrist also, and so we we uh we really had no idea from the beginning what it was gonna be like. And I mean, I'm sure that David had a a better image than I did, but it it was it evolved very greatly, and uh we just are thrilled that it came out the way it did. We we've had we won the Audience Choice Award at the Mill Valley Film Festival, which is quite a prestigious festival. And the the scientists that were in it make such uh complimentary statements, like Eric Verden said, it's an absolute masterpiece. And uh Steve Horvath said uh it was phenomenal, it's a wonderful film. You know, virtually all of them are very complimentary. I mean, notwithstanding the fact that some of them are in the film, but it's I think it's quite objective in in the uh treatment of the various uh things that might be controversial.

SPEAKER_00 25:23

Yeah, yeah. I thought of the the film was uh i incredibly balanced and very easy to watch. You know, I always feel like my wife is like, yeah, yeah, another longevity thing, you know, she sees me, you know, taking all kinds of supplements and doing crazy exercise routines, or you know, like we're just talking about fasting. Uh usually I fast from Sunday night to Tuesday morning is kind of my once a week fast. So it just works best for my schedule because I love a good coffee and and avocado toast too much, and I also like my dinners, so I try to get it just out of out of the way. But anyway, she was able to watch it with me and and really enjoy it as well. And even my five-year-old son, he he got a kick out of some of the animations and stuff, even so,

Cellular Benefits And Inflammaging Explained

SPEAKER_00 26:04

Jim. I want to talk to you, just double-click back on fasting for a second. So for the listener that might be hearing this and be like fasting, and just immediately tunes out because it's you know, it like you said, it's it's it's a hard thing to do, right? To deny your body like, hey, I'm hungry. Okay, let's not eat for longer, you know, is this like natural response that I think we a lot of us have. But sometimes when I at least when I talk to friends, I know like they're like, yeah, intermittent fasting, whatever. They kind of tune it out. But I would like you to maybe elaborate on why simple just fasting works at a cellular level. I I know you talked about the immune system a little bit, but can you explain a little bit more of what's going on in our bodies when we do fast and why it's so good for you?

SPEAKER_01 26:47

Yes, it's uh the it's the first step in a long series of changes that occur downstream, as they say, that result in the formation of various helpful molecules and the suppression of inflammatory molecules. The uh the the net effect is that there's a a reduction in in systemic inflammation, which I think probably most people are aware of, is a is the the main action of the of the physiology of the body as you get older and as you get past 50 or so, the amount of inflammation increases, and when towards the end of life it is increasing logarithmically. So this inflammation can be suppressed by the the cellular and the molecular mechanisms that that fasting induces. Um I don't I mean there are there are a number of uh strands a number of molecules that are formed, like the the the adverse ones, as I mentioned, are TNF alpha tumor necrosis factor alpha, that is responsible for rheumatoid arthritis. There are now medications that block the effect of TNF alpha and have produced miraculous results in people that have severe rheumatoid. And they also use these uh blockers for medicines that uh that that are medicines for ulcerative tollitis and and and other really potentially severe diseases. The I say that the if somebody is interested in the the molecular changes and the downstream kinds of effects, they could find a a chart on the internet, uh just look up inflammaging. That's a term coined a few years ago, meaning as you get older, for some reason that's not really understood, the the amount of inflammation increases and it causes damage to the the cell, all cells, and the uh the suppressive effect of the fasting reaction to it is is highly effective. I mean there's no there's nothing that is comparable to fasting in trying to slow the aging process, really. There are a a bunch of factors that uh I don't see any point in using the w the terms for because they're they are not really rememberable. But uh it's uh it's it's uh this is all worked out pretty well. Um if you just uh look for it, you know, on on the internet, you'll find uh a description of why inflammation is the number one cause of aging. It's um and there are there are a number of supplements that are used to uh counteract that. There's evidence that nicotinamide mononucleotide, which is a precursor of NAD plus, is effective in suppressing inflammation, protecting the central nervous system, as are others, such as urolithin A, N-acethyine. And those are uh over-the-counter supplements that can be used to reduce the amount of inflammation. And I take several different things that have that responsibility or that effect. And the the fasting part of the picture is at least as important as any supplement. To try to differentiate the benefits from supplements versus fasting, it would is a little bit difficult or has not been exactly worked out. But uh, metformin is a drug that uh there's been an attempt to categorize as a life-prolonging drug, but the FDA does not consider life a disease. Near Barzalai, who is in our film, has spent several years working on getting this study started because there's clear evidence that metformin w prolongs lifespan in people in a number of large studies. Um as as there are four other supplements, but the the exact molecular function is not often worked so far it has not been worked out. One one of the more recent uh supplements that I think everybody would be wise to take is spermidine, which activates autophagy, which is the process in the cells of eating the the garbage proteins that are misfolded or made incorrectly in their they just clog up the uh the cellular works and the uh spermidine causes those that garbage to be picked up and chewed up and and re-recirculated into uh healthy proteins. Uh and those phenomena, that is the uh autophagy, is also uh induced by uh starvation or calorie restriction or reducing your intake. And it's it I think the the best thing to say would be that if you try to do some kind of fasting every day in the form of alternate day fasting or uh eight, eight and sixteen, or one that you can tolerate yourself is is a very good idea. And there's there's an abundance of science that has shown that those things prolong lifespan, or since we can't really measure what the effect on lifespan in humans is, we l we look at biomarkers of health and reduction of inflammation. And there's no question that these things occur with uh both fasting and using something like spermidine.

SPEAKER_00 32:56

Yeah.

Autophagy Supplements And Natokinase

SPEAKER_00 32:57

Yeah, one thing that you just kind of touch on there too. I I guess earlier you were talking about Volter Longo and his fasting mimicking dialet, which I always thought was pretty interesting with like prolon or something like that. I've even heard Peter Tia talk about, you know, just making a salad with, you know, five olives and a little bit of olive oil to hit that whatever 600, 700 calorie mark for the five days, which is also really interesting, you know, just to do that. And then I'm sure pairing it with something like spermidine, you know, is like do you talk about the cellular trash, but I always hear laugh at the the coined term of uh zombie cells, right? You know, it's like clearing out the zombie cells of of uh, you know, with that.

SPEAKER_01 33:36

So that's true too. The the the uh stenolytic substances, which are effective in getting rid of senile cells essentially, are in combination, I think, quite effective. And uh there's more and more known about that. And uh I think most of the people that are in the field take one or more of these things like physicin and quercetin and uh there's a whole range of things that are have come to light as being effective polyphenols. And uh the I think the best the best new thing that I've heard about in the last year or two is uh natokinase, which is you may be familiar with it. It's uh a product that is derived from natto, which is a Japanese food that is made by putting soybeans on rice plants, which have a certain bacteria that cause the the soybeans to turn into a uh something that you probably wouldn't like eating, but the Japanese do eat in certain areas and and not in other areas. And it's been shown that the in the areas where they eat natto, their incidence of heart disease is about 50 percent of those who compared to those who don't. And it works by the natokinase is an enzyme that breaks down fibrinogen, which is an element of plaque. And if you you take it on a regular basis, and I'm talking about a thousand milligrams a day, it uh it reduces the plaque burden in your entire body by about thirty-six percent, but after a period of eight months, which is a remarkable benefit, and I I enthusiastically take it and endorse it.

SPEAKER_00 35:26

Yeah, uh I remember first hearing about natto and natokinase, I don't know, years ago, and I was like, I'm just gonna go try some natto, and uh I was surprised that it's a very interesting taste to say the least, but uh but yeah, I will say like if you've never tried natto, go try it just because it's a very unique um thing and just all itself. But yeah, nano kinase supplement is a much easier thing to take and digest tolerable.

SPEAKER_01 35:53

I think generally speaking, I would just say to try to to try to fast every day. Um you can just not eating all day and uh one meal a day is is beneficial. The most effective thing, though, is alternate day. I think the evidence is clear that if you can reduce your intake by by about 80 percent on the the alternate day, you can have remarkable effects on the levels of inflammatory markers.

SPEAKER_00 36:24

So you're saying one day just eat as you normally would, breakfast, lunch, dinner, coffee, tea, all that, and then the next day you're saying cut your calories down to about eighty percent of normally what you could. So you could still potentially have a coffee or something, light meal.

SPEAKER_01 36:38

Is that is that where you say No, you you cut it down to twenty percent. I mean, it doesn't have to be that severe. There was a study done by a Spanish uh gastroenterologist in the 50s named Olefo who had a he was in charge of a nursing home, so it was all people 65 and older, and divided there were 120 residents, and he divided it in in two groups, one which just ate the normal cafeteria food, which was a well-balanced meal, 50 grams of protein, you know, standard kind of good proportions, and the other that every other day got a quart of milk and 500 grams of fruit, which amounts to about 900 calories. So the reduction, and they this we we wrote a paper on this, correcting a previous observation that was incorrect. The level of calorie intake when this was done was probably about sixteen hundred calories a day. And so on the day in which they were eating a low calorie diet, it was 900. So the difference there is, you know, maybe a 40% reduction. And at the end of three years, there were uh significant differences in the in the health of the two groups. There were three times as many deaths, but it was not significant statistically. But in those people who were on the milk and fruit program every other day, they uh had very statistically significant reduction in visits to the infirmary, which is is correlated highly with mortality. So if you carried the the uh study out longer than three years, you would have seen probably a lot more deaths. The one of the greatest predictors of of uh future death, near future death, is the the occurrence of the visits to the hospital within six months of the of the time of the time of death. And so the significance of it was uh even though it it lacks some some significant data, but it was it was clear that they were only eating the difference between probably 120 percent of food on the the day when they were eating the cafeteria food, and uh the other, which would be uh something like 40 percent of their daily requirement. So it doesn't have to be as severe as 120. Uh that was just my original design. And so it's I think it if you can cut down your caloric intake by 50 percent, you're probably getting uh sufficient stimulus to uh experience benefits. And these things will be worked out in the future, I'm sure, but it's it's a slow process simply be because doing a study like that would be a very expensive process nowadays.

SPEAKER_00 39:37

Yeah. Yeah.

Practical Fasting Rules And Real Results

SPEAKER_00 39:38

So you're so Jim, you're not theorizing any of this. You're you're actually living this in your day-to-day life, obviously. You know, when you're younger and you found out you had the the heart condition and stuff, this kind of set you on this path. So what does a normal day look like for you for for now? And then you kind of alluded to that you've changed your approach as you got older, not necessarily that you would be doing the same things, you know, say 10, 20 years ago, but what does your day-to-day look like now, and how's that kind of changed a little bit over the last, you know, say 10, 15, 20 years?

SPEAKER_01 40:11

Right. When when I started, I as I said, uh people thought I was nuts because nobody had ever done it. And uh I had some ridicule and I d uh for three and a half months I followed the the hundred percent, twenty percent. I said it wasn't actually a hundred percent, it was uh eating ad lib, so I might have eaten more than a hundred percent, and that doesn't seem to matter. But on the down day, the low day, I stuck to as close to twenty percent. I liberalized it a little bit so that uh it was uh raised it to about five hundred calories a day on the down day. That's that's more feasible, it's much much more pleasant. And in the study we used uh canned shakes because it's difficult for people to estimate exactly what the food that they're eating is, and if you give them the option of a salad, for example, they'll put on you know five tablespoons of salad dressing that have sugar and and and oil in it. And I think that's the only way that you can really start on it because otherwise you j you just you misjudge. You say, I can have this hot dog on top of this uh piece of tofu. But you know, it's it's it you have to have certain restraints at the beginning. And there have been other a number of other formulations that that have been effective. There's a woman named Krista Veridi that's written several papers on this, and uh she really kind of uh dominates the field or did after the uh the early when I wrote my paper and which was published in 2006. But you know, the popularity of the diet or the the belief that the diet was effective has grown over time. In 2018, the most popular diet, I guess nationwide, was intermittent fasting. Intermittent fasting doesn't mean anything because it it doesn't define exactly what you're talking about, but it's uh there's little doubt that fasting of some sort is very effective. And what you're doing is very effective one day a week. That's a that's a very uh admirable program to follow. There are years ago there was a study in the in Mormons that fasted one day a month, and and they had a 40% reduction in the incidence of heart attacks just from one day a month. But it's the what I was convinced by the when I first started it, and I I lost 35 pounds, and I had a patient who was asthmatic, and I that's what where I got the idea of using overweight asthmatics as the subjects because I wanted to be sure that they were going to be motivated. And she had she used two inhalers twice a day, and after three weeks on the diet, she was off everything. And uh it really had some really remarkable effects. Another woman was 69 years old, it had meningitis ten years before, and it seriously damaged her balance. And she couldn't walk without having somebody support her. She had to get her get weighed, she had to have two people, you know, help her stand on the on the scale. And, you know, the balance is dependent on the health of the vestibular nerve and the vestibular nucleus in the brain. And the she was on the diet for three weeks, and she came in one day and said she could and she was walking without assistance, having been really disabled by it for ten years. And you know, I it's it's hard to really reveal what what uh is happening there. But it has to be because of inflammation in the brain at some point, you know, in the vestibular mechanism. And uh I had I mean there were many other amazing changes just in an eight-week period. The palmetologist said that the as a as a whole, the group had been raised by one category of severity with their asthma, and they lost about 19 pounds, I think, during the eight weeks. So the the reduction in inflammation is a measurable biomarker. I mean, if you uh if you have sinusitis, it it goes away, or if you have uh some kinds of arthritis, it it goes away within two weeks or so. And I had several of the people continue following the diet for for many months thereafter. I didn't I lost contact with them eventually. But there it's if you look for it, you will see that there are things that are happening to you that are favorable and you feel better and so on.

SPEAKER_00 45:04

I love that. I love that. I I I just love seeing especially something such as simple as fasting, where a lot of things I talk about, you know, is like there's uh a a vast divide between a lot of longevity and anti-aging stuff is is very expensive, right? You know, very experimental, or even just having a longevity doctor is quite a financial uh uh commitment. And a lot of people can't make that jump financially a lot of times. And so I love hearing you talk about something such as simple as fasting. Yes, it's difficult, but it's also free, you know, or or low cost, if nothing else, and likely even saving you money because if you're eating, you know, it's like every other day or whatever. So but also having the the compounded benefits of over time of something like that of obviously the more you do it, the longer you stick to it, it sounds like greater the benefits of you know, like weight loss eventually and inflammation and and all of that. So that's it's just such a cool thing to hear you talk about. And then you're such a pioneer in the space too, you know. It's like it's like way before everyone was, you know, the Instagram influencers and and and so many people are talking about it like it's the greatest thing since sliced bread nowadays. Um but it's just really cool that you've been doing this and investigating and actively researching and even just with the bike study with the Buck Institute and stuff, like you've you've truly believed in this and and funded research and and really has has shown that it to be quite an effective thing. So that's just an amazing contribution. And I I I mean, I just want to personally thank you for being involved in it and pushing the needle because you know there's so many people that reap the benefits from you know that that research, or even just like that first time you went to the Buck Institute to, you know, help them along with, you know, the clinical trial, you know, to it's just super amazing. So I, you know, just thank you for that. So and I also want to wrap this up because we've been talking for about an hour now, and I want to respect

Forever On Film And Where To Follow

SPEAKER_00 47:02

your time. And how do people find out, you know, I mean, we talked about the Forever Young film that you're in. Um, are there any other ways that you know people can find out more about you or the research, or should we direct them to the Buck Institute?

SPEAKER_01 47:15

Well, we have a s we have a substack, uh, I think it's called Forever Young Movie, and we put articles on there regularly. We have something like 80 or 100 articles, as well as videos that are instructive, and and we try to uh find subjects that are not covered elsewhere. I mean, certain people like Peter Ati are going to systematically through the cardiovascular system and the GI system and so on. And we tend to we try to be eclectic and and pick things that are maybe not not uh as uh conspicuous as as others and and we we get good feedback. One of the things that we reported on is the use of bisphosphonates because there's apparently a very strong pro-survival effect. It's very good for longevity. And I would you can if people can find our our articles. If people want to know the the basic uh concepts, they can read uh articles by Mark Matson. His are very clear and he's the original. And I learned from him everything I know, and and uh he's a wonderful man and and surely devoted scientist. I mean, he just doesn't waste any time.

SPEAKER_00 48:35

Yeah, he he's a legend.

SPEAKER_01 48:37

Right. He is, and he's he's a great guy.

SPEAKER_00 48:39

And for those listening that might want to look him up, his last name is spelled A-T-T-S-O-E. Just so you know, if you want to do some research on him, he's I think he still works at the NIH, right? I think he b I believe he does.

SPEAKER_01 48:52

He retired from that and went to Johns Hopkins about six or seven years ago.

SPEAKER_00 48:57

Okay, okay, okay.

SPEAKER_01 48:59

I'm thinking I'm gonna contact him and we're gonna do a I hope he will do an interview on our substack.

SPEAKER_00 49:05

Yeah, that'd be great. And then also we have the the article you wrote on our website, Spanner, S-P-A-N-N-R, about the longevity mindset that actually uh we're gonna have that go live probably right when this podcast is going live. So especially now that the film is officially released today, uh it's kind of waiting to publish all of that and then have that. So I had David's episode go live a week or two ago, and then we'll have yours go live as soon as possible, as well as that article about the longevity mindset. So that was a super cool article. And again, I appreciate you writing that and and able to guest post.

SPEAKER_01 49:42

And I will make sure this is my mission, you know. When I retired, I decided they all everybody says you have to have a mission. This is the only uh thing that I would consider to be making my mission, except learning to play the guitar.

SPEAKER_00 49:57

Yeah. Well, I I was gonna ask, do you have a band or is it just a solo project at this point?

SPEAKER_01 50:01

No, I'm uh I one of my grandsons has really passed me up just uh period of a year. He's amazing. And but I do it just I take one four-hour lesson a week with a a very with a professional musician, you know, and I love it. I I know uh yeah, for that four hours I'm in a different world.

SPEAKER_00 50:21

And uh Yeah, I feel like it's like that's one of the keys to staying young too, you know, keep constantly learning, you know, that that mindset of always learning things, whether it's the language, music, what you know, what whatever it is, but you know, it's like having that healthy part of it. So Jim, thanks thanks for coming on today. I really appreciate your time and your just wealth of knowledge. I I wish we had four hours to just go into everything. And uh it does take time. Yeah, it just it just time flies. But uh, and I hope to meet you in person at some point. Like, you know, I was talking to David about getting together with him at some point, but but yeah, maybe we'll see you at some longevity event or at the Buck Institute at some point in the future.

SPEAKER_01 50:57

But do you go to the some of the events? Yeah, yeah.

SPEAKER_00 51:01

I I try to do as much as possible because I've I've got three kind of longevity businesses. One is the longevity clinic marketing that I help clinics get found online. So that's kind of like my MO is because when I was looking for a longevity doctor in 2017, I didn't even know I was looking for a longevity doctor. I just wanted a good doctor. And then I stumbled across a great doctor uh in Austin, Texas. They run a peer on, Dr. Dan Stickler and Dr. Michael Hamilton. And they just gave me a whirlwind of an education while I was under their guidance and care. And I was just like, I really need to find more of these practitioners. And so I took my whole marketing agency that kind of worked with everyone, and they just completely shifted to the niche of longevity because I've just so interested. I love talking to people like yourself and practitioners and clinicians, and so that's one of it. And then we have Spanner, which is kind of the longevity umbrella of everything, and then of course this podcast, the longevity loop podcast. And so, you know, I feel like my mission is as well is just, you know, like get just getting people excited and more people tuned into this kind of medicine because it's so life-changing, you know. It's like my parents, like, you know, just getting them tuned into it and so they can extend their lives and be healthier, like moving forward. And and my son, you know, it's like being five is such an incredible thing to hit for him growing up in this environment that like, you know, the possibilities are endless, I feel. So it's it's just an exciting time.

SPEAKER_01 52:27

I have no doubt that uh what David Sinclair says is gonna turn out to be pretty much what we expect in the next few years. I'm very excited about it.

SPEAKER_00 52:41

Yeah, I love his book. I mean, still like the hi his book is just one of my favorite kind of just foundational, you know, and even you're talking about Mir's book. I I think Age Later is his first book. But yeah, I mean, just yeah, there's so many good books out there, and just so many people just do an awesome work. So with that, Jim, just thank you again so so much for coming on. And uh and then I'll put the links to the Substack and the movie on Apple TV and everything in the show notes so anyone listening to this can easily find all of that stuff. And I'll also link link to Matson's work and and and a lot of that stuff because it's it's all awesome place. So with that with that.

SPEAKER_01 53:17

I think I think you're doing a a a great thing with what you're doing. I mean I'm you know, I feel like I'm part of a a team that is sort of motivated one individual by individual, and that it's uh it it gives me great pleasure.

SPEAKER_00 53:34

Yeah, yeah, it's exciting. I mean it's a it's a great community and it's just always so much fun just to run into I I mean, just so many brilliant minds. I mean it that's that's the thing that that that I'm just always floored by is like how many smart people are involved in this space and I don't know, it it it's just a cool time to to be part of it.

SPEAKER_01 53:50

Wait till you talk to Tom Lewis, talk about brilliance.

SPEAKER_00 53:55

Yeah, we got him scheduled, like I said, like neck next week. Uh I think that's when he comes on. So yeah, I'm super excited to talk to him as well.

SPEAKER_01 54:02

So we're gonna we're gonna go to uh Cape Cod and give a screening to or a couple of screenings to the Harvard Club June 17th, and we're excited about that. We were invited by another podcast host to do it, and he's he said that film is a national treasure.

SPEAKER_00 54:23

It's amazing. That's a great compliment. That's great. Well, cool. Well, thanks again, Jim. Thank you very much. And we'll be in touch, I'm sure. So take care. Bye-bye. Bye. This is the Longevity Loop Podcast.