Rapamycin for Longevity in Clinical Practice
Rapamycin (and its analogues) is the powerful mTOR inhibitor [and ITP favorite] that has extended the lifespan of organisms from yeast, worms, flies, and even middle-aged mice. The physician with arguably the largest clinical experience in prescribing Rapamycin for longevity talks about the challenges and benefits of this fascinating and controversial practice. Dr Alan Green takes us on a deep dive on the use of Rapamycin for longevity.
Take away points:
-Rapamycin has extended the lifespan of organisms from yeast, worms, flies, to even middle-aged mice.
-In a 2014 paper, rapamycin extended the median lifespan 23% in male mice and 26% in female mice.
-It is an FDA approved prescription drug with indications for use for the prevention of organ transplant rejection and for the treatment of lymphangioleiomyomatosis.
-The drug requires a prescription and should only be used under supervision of a physician
-Rapamycin acts by suppressing the master nutrient sensing protein mTOR [mechanistic target of Rapamycin]
02:45 Blagosklonny papers (Blagosklonny 2019)
05:23 Jane Mannick rapalogue paper (Mannick 2014)
08:04 Cardiomyopathy diagnosis : Apical hypertrophic cardiomyopathy
09:14 Elevated mTOR as common factor- Inflammation, fibrosis,
12:03 Rapamycin role to decrease mTOR overview common pathway
14:23 mTOR is essentially command and control of the cell for the last 2 billion years
15:00 Mitochondrial complex 1 affected by common pathway by rapamycin, caloric restriction, protein restriction, methionine restriction has universal anti-aging effects
16:05 Increased mTOR causes increased innate immune system/inflammation
17:28 2009 paper showed increased mouse lifespan not by just decreasing cancer but most other diseases of aging
19:15 Osteoarthritis inflammation improved by decreased mTOR and increased autophagy
23:00 Alzheimer disease as a disease of senescent cells
26:00 importance of dose timing for Rapamycin
27:00 Anti aging effects on mTOR1 and other effects on mTOR2
32:00 Rapamycin as off patent drug
37:00 Dosing considerations and subjective effects
40:00 Tracking HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) score
42:00 Improvement in exercise related to maximum cardiac output
45:00 Age associated cardiomyopathy
49:00 Untoward effects- Aphthous ulcers and decreased innate immune system. Be on guard for bacterial infections.
57:00 Personal lifestyle choices
https://www.mdcalc.com/homa-ir-homeostatic-model-assessment-insulin-resistance
Blagosklonny, Mikhail V. “Rapamycin for Longevity: Opinion Article.” Aging 11, no. 19 (October 4, 2019): 8048–67. https://doi.org/10.18632/aging.102355.
Harrison, David E., Randy Strong, Zelton Dave Sharp, James F. Nelson, Clinton M. Astle, Kevin Flurkey, Nancy L. Nadon, et al. “Rapamycin Fed Late in Life Extends Lifespan in Genetically Heterogeneous Mice.” Nature 460, no. 7253 (July 2009): 392–95. https://doi.org/10.1038/nature08221.
Mannick, J. B., G. Del Giudice, M. Lattanzi, N. M. Valiante, J. Praestgaard, B. Huang, M. A. Lonetto, et al. “MTOR Inhibition Improves Immune Function in the Elderly.” Science Translational Medicine 6, no. 268 (December 24, 2014): 268ra179-268ra179. https://doi.org/10.1126/scitranslmed.3009892.
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Robert Lufkin 0:02
Welcome back to the health longevity secret show with Dr. Robert Lufkin. Today we’re going to hear from the physician with arguably the largest experience worldwide in prescribing rapamycin for longevity. Dr. Greene is a Board Certified pathologist currently specializing in the treatment of age related disease. He has an MD from the State University of New York Downstate Medical Center College of Medicine, and a residency in anatomic and clinical pathology from Winthrop University Hospital. Now, rapamycin, also known as sirolimus. rapamune, is an FDA approved prescription drug with indications for use for the prevention of organ transplant rejection. And for the treatment of lymphangioleiomyomatosis. Any other use is off label. rapamycin should only be used under the supervision of a physician. The information in this program is for educational purposes only, and is not medical advice. Please also see our disclaimer at the end. Now, enjoy this interview with Dr. Alan green. Dr. Green, it’s a pleasure having you on the show. There’s so many things I want to ask you about your practice, but maybe start off just how you became interested in the study of longevity.
Alan Green 1:24
Well, about the early Sue like it, but just as I turned 70 and occurred, it seemed to me that I was sort of like having a very rapid decline of my health. And based on the rapid decline, I thought I was going to be dead in a few years. And I mistakenly thought that I was suffering from aging. That was so I didn’t know anything about at the time. So like most doctors, I had zero knowledge of aging. But I had like confidence that I could look up aging and medical textbook and find out what I’d like to know about. So I looked at medical textbook, and I was absolutely amazed to find that it wasn’t there. I mean, I just I be I was so flabbergasted, I was like looking through all these books, looking at the index, like in the table of contents, he is simply not there. And I’m like blown away by this. So then I decided to sort of like start studying aging on my own. And, like the first thing I came across was this de de de like UK about Metformin and that people taking that form and we’re living longer than sort of like non diabetics, none of it formal that was like, that was like amazing that that anything like that could happen. So that’s really got me like interested in that there might be something to this and eventually I came across like lack of scaloni now I was just extraordinarily extraordinary impressive blackice flurry us the only person who was like making any sense of lack of clarity just had an extraordinary Philly conception of the whole thing. So after like studying black skies works to about like six months and shading everything had to say I say is that I which tie is like, formula like that the bison is like suggest to take that but I said it’s like 2006 paper. And so you know all this paper since then. So this is sort of like January 2016. Now prior to January 16 and December like paper that came out Christmas Eve and 2014 by Jay Matic like that changed everything because prior to that paper, it seemed that you can take that the Meissen because it had an adverse effect on your immune system. Well, Jane Mannix has showed that no that was just a case of how you were taking it when she gave it to people like once a week for a short period of time. Like she showed that she had an improvement in just like acquired immune system they had a thorough response to like oh like flu shots. So that changed everything. That meant that if it wasn’t having a bad effect on you, it cell function acquired a new system that made it safe so I decided to sort of like try it. And I like you know by going to score it’s like papers, I decided to come up with a dose of sage 60 milligrams once a week because blackest glow was real queer. They actually used internet only. And wagas guy also had a paper in which he said that they gave a six milligram dose to volunteers and it had an effect. So like six milligrams seemed like a therapeutic effect. anti shame like, pretty good. So I decided I would just try that I was trying to have like a high dose because I wasn’t too concerned about side effects, I was much more concerned there is simply, when I have any effect, I was not really expecting much of an effect, I had very low expectations. So I like started like January of like, 2016. And going along, and by like, you know, like three months. And so I am just blown away. I am like, unbelievable. I like feel like I’m like five or 10 years younger, I am not settling for any distress whatsoever. Prior to that I was suffering from severe. So like, like, you know, definitely like heart failure, like an early stage of luck, failure. And then I exercise I get like, like signs of like heart failure, chatons addressed and both things like that. So now, but now I’m just doing unbelievable, I’m not having any symptoms whatsoever. Like pick up cycling, I’m riding my bike like 1000 miles one time, like feeling fantastic. I just could not be so like dealing in better shape.
So I’m continuous going along with that. And I said, Well, this is like the greatest thing ever. I can’t believe how great this stuff is. The only problem is, if you were in a position you can’t get. So I feel like that was there wasn’t any way to get it. So I figured, well, if this continues working in like really, very good like this, after a year, I like open up a little practice, since I’d already been retired for 10 years, I said that ologists I had no intention of starting fact. And so I just decided that I didn’t make this available. For a few people who were like studying all this or like the literature, they decide they want to use the APA license, but they didn’t have any way to get it. And they didn’t really know quite how to use it. So I just thought I’d do that. So I just set up an office and I parked my house is like so it’s like zero overhead. And it was just set up the practice that I would say like knowing two patients a month. That was perfectly you know, that is that was the idea. No overhead, the two patients in mind who people who had like made a special like especially interested in this and want to try it but they were in a position so they could write a description. So this is going on that first page patient and make a march of 2017 is going Oh great. And then like a couple years later, I have an opportunity to have an echocardiogram. echocardiogram, I find out. I wasn’t suffering from aging at all. I was like totally not suffering from aging. That was like totally not what was I had like an extremely rare cardiomyopathy. And that’s what I had. And then I realized, well, then it’s like, I realize that’s what my mother died from. That’s what my grandmother died for. That’s how there’s no old people on the other side of the family. It was like an autosomal dominant cardiomyopathy. And that’s what sir, like people like that’s what they had. They initially they initially it was I am presented with atrial fibrillation, my 50s. But there was no other flattening. And both my mother and my grandmother, they had died for like complications of atrial fibrillation. But other people I die from complication to that complication. So it’s like real clear that that’s what people had is like a very bad thing is atypical hypertrophic cardiomyopathy, which is like, say cardiac hypertrophy, primary apathy is rare. And this was about 5% of those cases. So it’s like, wow, that was quite remarkable that that responded, terrific to rapamycin, which turns out to be most of our hypertrophic cardiomyopathy is C spine to about the waist, in case it doesn’t, doesn’t seem to matter too much about what the initial genetic code says. And they all have this whole big wide array of an array of different genetic causes. But they’re common. So like the denominator, at the end, is a, whatever is going on, they wind up with elevated and to a to M to a stance, we’re talking about the license to that elevate m to a, and that’s what’s causing hypertrophy, that’s what’s causing that fibrosis, that’s what’s causing inflammation and the disease process. So, Jay, so that that was so that I was simply a case of complete work, that I feel like wound up with this because if I had done the right thing, and seeing a cardiologist the cardiologist would have done an echocardiogram and they said, Well, you have this cardiomyopathy and come back when you need a heart. Check. Plan.
Wow. There was zero treatment available. Silva is doing great. And I like Intel realized that the license worked extraordinarily well and all sorts of things. Curiously, I found there was something like this or like a patient and a couple of brothers who had an addition, additional, like a different extraordinarily rare quality mouthy Lamin a Claudia my opposite it’s like that. I never even heard that. They did great on rapamycin that is like day to day they doing like was like the one person he was at the festive. So he did some independent research and he found out that people were treating a mouse now that is exactly bison. Do you want to try rapamycin? So he did people here Derek identical treatment, but they weren’t getting a map, the wikia map amazing. So I came he extraordinarily good response and went back to like teaching full time. So I did like, a lot. So after my son turned out to be real, real good for hypertrophic cardiomyopathy. Oh, I had like a very nice like practice, I realized it seemed to work with just about all sorts of things that seemed to work, but mostly, all the age way diseases that were especially associated with increased risk with diabetes. So if you had an ace Ray disease, and people with metabolic segment syndrome, overweight people, diabetes had an increased risk, randomizing work with that, because all those people, they they were they was all elevated and to diseases, there is going to be like a few other states or like a more unusual age where diseases that don’t have that. If you’re at an age where disease occurred in 10 people, there is less likely that elation will work. But because of that people increased with that device it was going to work.
Robert Lufkin 12:11
Maybe for our audience, you could just go over some basic fundamentals about how what how, how does dialing down mtorr as a nutrient sensing protein, how can it affect all the so many diseases like that?
Alan Green 12:28
Well, effects all diseases, because it looks like all diseases have a serve like a common pathway, because that the Meissen is only doing one thing. So this only effect is to decrease mTOR. And if you can use it, and how you use it, it’s decreasing mTOR One, and two or two. But it turns out that mTOR is basically at the center of everything that’s going on in the cell. peculiar thing, so mTOR is basically then the command and control the cell for basic seems like the last 2 billion years. And how you can trace it back to 2 billion years is because it’s in the plant world, as in the animal world, and they can sort of like trace that that sort of like split between a one celled animal that was a common ancestor splitting into say, like the vegetable world on the side, and the animal world and the protozoa side. That was basically 2 billion years ago. So is it amazing?
Robert Lufkin 13:43
Yeah, that we can see the we can see and tours as a major signaling protein all the way from yeast to human beings and, and turning down mtorr has longevity benefits. And every single one of those animals and plants that
Alan Green 14:01
it sees, there’s like a couple of that there’s like two genetic different effects. And two, I seems to what to like increase longevity by working on mitochondrial complex one. And that seems to like work on there. And it seems that seems to be in common with a lot of pathways. It seems like you get turned down by a complex one with like caloric restriction, or like protein restriction, or refining restriction, or rapid Meissen, they all seem to have the same sort of way, like, like changing the mitochondrial function. So, so that empty to that complex one is less sloppy with ends with electrons to sort of like describing once they’re away. Now the words that this like less sloppy was spilling edge. with electrons, that slows down, that causes less DNA damage and slows down aging, that seems to be sort of like a common sort of like technique for controlling aging, because when the other sort of like several very, very slight top researchers, it is like Baja, or something like that really can David like saying he showed that that was what was going on. It’s like controlling aging, and different different species that he was having, like you had like a bird, which is the same size as a rat. And the rats have been three years in the bursary 30 years. And he was showing it was like basically, it was like that mitochondrial function that was doing that, that how they sort of like adjusted the mitochondria would affect like a dot factor like that. So that was one thing that there was like that my son is doing. But the other thing that was doing is just an attorney down like M to M to a sideslip, this direct mitochondrial back was having a very adverse effect on just about everything, as far as age related diseases. For one thing, one thing was doing very directly it was causing increased inflammation that it was it was having a direct effect on what’s called the innate immune system. Now, the innate immune system is involved with inflammation. And like macrophages, it’s not acquired immune system, but that that system, and OFAC response to that system seems to be involved. And downstream, this like huge all these like, don’t like new nuclear attack, okay, they deserve like, you know, and then all these other factors, all these different factors, which is causing like inflammation, and like, damaging effects on all sorts of like diseases, it’s tearing us down. That seems like So this seems to be like a host of like this huge ship and things. And they all seem to get involved. And like diseases because it’s
basically a side, I say about 2010. Now prior to that I in 2009, that was the first time they showed that randomization increase the lifespan of mice. So money show to increase the life span of mice. And it showed that was it just decreasing cancer, they were they evaluated, they could see it was slowing down aging, that was sort of like the that was the general consensus of what it was doing. And it’s not just decreasing them that the mice is risk of cancer, it was really slowing down aging, because it was affecting, they could see all the other so they can see all sorts of other things like flies and worms that didn’t get cancer, it was increasing their lifespan too. So it was having a real effect and slowing down aging. Well now all the different, like researchers started looking at what mtow was doing, and all the different diseases, like none of nobody was interested in reclamation. They were interested in what’s the what’s the pathway, and these different diseases, what’s this, what’s the actual like cellular pathway, like molecular pathway, and what is sort of like mTOR doing and what happens when you turn it down into it. So they’re all using rapamycin, just to turn it just as a convenient tool to turn it down into a second see what well enjoys playing and all these different age related diseases and basically almost all the diseases so looking at Anatolia is in the middle of the disease and basically where the sort of like top research scientists said it’s a disease a scratch in the middle of it you’re fine You’re trying to enter in the middle of that disease driving that disease lowering into a is like status like lower like stopping disease it’s sort of like going on with like, things you won’t even think like that. Like I mean like things like osteoarthritis I mean I’d like to do it right away person is like aware of Town Car like thing that turned out there was no wear and tear tie thing. It was an inflammatory kind of thing. And if they turned down like enjoy it, they would have they would like these like very much improvement to disease because they were increasing our tapa g so the cartilage cells are still surviving that better and they were decreasing the inflammation that was a destroy the Highland cartilage. So it’s like even like the thing like that. It’s like amazing that disease like that was that will lead to a disease. He said the same thing. Yeah, I was like these basically it’s like one disease after the other, that
Robert Lufkin 19:56
maybe the degenerative changes. I’m a radiologist by training. So I, you know, I was looking at all the degenerative changes over the spine and everything and in Yeah, we were taught that, oh, that’s just age related degeneration, you know, wear and tear like you say, but but the evidence now is is that no, this is a specific amatory process.
Alan Green 20:18
Yeah, amazing thing. Every guy in the spine is when they came up with showing that the spine was a senescence cell disease. Yeah, it was, yeah, it was like, it was like senescence cells that was damaging to cartilage. And they’re like, by reducing senescence cells in there. So like animal models daily. So like, we do, say, like that this disease, that was like the same section, that was the same, like, I mean, my understand is like, well, it just, it just dries out and dries out. And then it like, breaks down. I mean, the idea that it was like a laboratory, senescent cells, were actually sort of like dissolving the disk is an act of sort of like process. It wasn’t just these things weren’t just wearing out. They were being destroyed by either. And then the other that’s the other thing that was extraordinary. Yeah, this whole like blue sky train diseases that had been come together by being presented like really vague was blowing enter with that message, then you had the senescent cell people, and they come up with like, a totally different approach. No, like, if nothing ever, ever even mentioned em to understudies, they never talk about em. They just like learning questionis itself. And they develop all sorts of like, they used to stop to request to have to study for half the stage, they just come up with a dwelling survey thing to destroy Smith himself in that area. And they’re coming up with like the same sort of like, whole very long list of diseases that are being stuck. If you if you remove certain cells. And you look at this list, it’s like it’s the same list. Went disease, if there were diseases was one, it wasn’t the other is like no one had checked it yet. But basically, all on the same list. But the only sort of like big disease that wasn’t on that list was our son’s dow samesies. Because I get outside with these dailywell to show in 2010 some like great researchers. So like University of San Antonio toyshop Institute for like one of the world’s great research places, they showed that they could like two different groups, they could prevent Alzheimer’s disease, and right now smiles of Alzheimer’s disease in 2010. And they will continuously show like, you know, protecting that different words different sort of like models, everything else come along. But so that was like the only disease that is like, Okay, how fat This is mTOR is not this and cells that way. So that idea was totally exploded in 2018, when they showed that the major cells driving outside disease was senescence cells. It was like that they said, like, like I boosey from San Antonio. He was just like one of the people that made the first name on the state paper, they showed that the cells that everybody had been wondering about since 2006, that the new ones with the new February tangles that no one knew what they were sort of like doing because john one and they had known February tangles. On the other end, they kept on surviving and they weren’t like die. He showed that they would send this in cells that they were senescence cells. And if you remove those senescence cells with the sap to them, you stop the disease process. So that was absolutely extraordinary. That was 2018. And now San Antonio is doing an actual study with this optimum actually treating patients with the same sort of like this outcome routine, but that was just, that was just the start of it. That was just the new ones. And the same sort of like between 2018 2019 they showed that all go down to ugly, making violin. Davis to this they became senescent cells. And then microglia was listed. And he asked your site to solicit the whole group of all this sort of likes for all the players. Like the three different types of glial cells, and plus the new one with the new template tag, those will all send this in sells.
Robert Lufkin 24:49
Wow. Well, we before we get into this senescent cells that I really wanted. That’s very exciting just before we leave or before we transition from that forum, and and For our audience I we will link to all these important fundamental articles in the show notes. Everyone will have access to them on Metformin I mean I’m sorry, on on rapid mice and the you mentioned complex one. Could you talk just briefly about complex one versus complex to and why we why we dose why we don’t do continuous dosing of rapamycin?
Alan Green 25:26
I’m not talking about that until when when toto is talking about complex where the mitochondria, Oh, okay. Complex where the mitochondria, just as far as I can go with it. I don’t understand why school came with it. I should have like one, two and three and four. That’s it. That’s very, very complex. That’s your like the work. I’ve always say, like, no, I baja from like Spain who like showed that but as far as like that the mice in Napa nice. It has m two one and two. I two. Yeah, sort of like tricky, necessarily, like tricky thing that turned out when they introduced rapamycin, and 1999, and transplant medicine, they had no idea about a thing from anything. All they knew was that randomizing was like you can give the Lamb of affirmation, it alters the effect of the lymphocytes data recognize a fine organ didn’t recognize a dying kidney. You can do you could give it and you could use it for transplant medicine, it was more ever safer and better. The medicines I had for transplant medicine. And it had some side effects, but not a particularly sort of like serious side effects. But and what they knew is that you had to give it every day. That was what that was the Wednesday that they knew that you gave it every day and you maintain a continuous high blood level because the half life of rapamycin about 65 hours. So if you give it every day, you’re just building up into like blood level, and you have a continuous high blood level. And with the continuous eye level. That worked. And they never they knew why that worked. They turned out that other set of like researchers and cancer researchers figured out what was going on. And I noticed they’re like, well, it taught me searches in 2013 Sega and Sega two guys named that way now, here I said all the benefits of anti aging effects reducing and tau one. And all the harmful side effects with reducing m two I do. So if you just sort of like use it to so like reduce m to one and not reduce that to a two. That’s all you have to do. And that’s your like, so that was to sort of like key that was sort of like it is like no laughing because I’ve done through lightning. So if they want to came up with that idea 2013. So that was that was the key thing. The key thing was to realize that decided X to M tattoo and benefits the anti aging benefits and to enter one. And they’re both sort of like they both have very, very different like compounds, but they can see they’re on the same platform. The same, they laid it that way. But they’re like not related. As far as the function very much, the function is a quite different different. And it turned out that M toi. Two was 1000 times more insisted to have a bison for M to one. So when you just take a single dose of wrapping bison, you reduce them to one because I’m told one was set up in the body to respond to everything, right food, this that because it was controlling everything. It was the spine to mTOR when we spied everything out it wasn’t responding to anything. So it was just maintaining, like a level of function
of all these different things. So you never wanted to decrease mTOR to and transplant medicine. They introduced our device into be a biologic poises that was they weren’t introducing it to do anything good, whereby they were introducing it to poison the acquired immune system to alter the function of the lymphocytes. so that they could do better following kidney antibody would not react to it, which is a pretty deranged immune system to not react to a foreign kidney. But so that was an but why turned out with like they gave it every day is it was a case of M toi. Two is already formed. The pieces are put together. We all nice and tight. That my son can jump into little spots. Can’t like mess it up. But when you’re when the value has to be placed Enter to continuously add the weather to when you’re doing that, and by sooner, so it has to Nate what Enter to make em to add to, it has to build the little plots, and stick another little plots together, can stick together at a high level of affirmation, because we optimize and competes with some of the spots where the things go. So you can assemble a functional level of M to a to in the presence of a continuous high blood level of randomization. So and when they use it, they have like a level, no continuous high level of blood level that amazing and they check continuously, they do blood levels to make sure that the native or low level doesn’t get below a certain low level. So they’re keeping it a high level and that high level they keeping at that events to buy for making a functional and now add them to add to you don’t have a functional now then totoo works great for to transmit medicine, but it does have to have some significant so exciting things. And because it’s like you know, it’s not good. Insulin resistance is having an adverse effect there is happy that there’s a lot of adverse effects and but the bottom line was, those people receive know that they did not have a increased lifespan. Whatever benefit they have from decreasing m to one was overshadowed by decreasing m to a to z, I had a kidney transplant, but they did not get any sort of like beneficial side effects. So that was how it worked with that. But the power of rapamycin is a better way she got typecast as like a bad guy. And that a million people have used math to Meissen and transplant medicine, they will take it every day, they have all the side side effects, or show my synthetic every day is not good for you. And your capital TDI you I was just excited. Thanks. This is nice, it’s like not good for you, when you take it every day. Because it’s it’s all the side of things that we do see em to add to. So based on that, it’s very difficult to other people to use it because it has all the side effects. And because we have to bison is a generic drug is called syllabus. Nobody’s selling a few 100 million dollars to do clinical studies to show that like, no, and they have to start off with like stage one class one clinical studies, it’s showing a safe way to use it just say using it once a week is safe. And that’s that before they can even do anything else. So it’s like people doing studies with it. You can’t have it if you want to have an FDA approved study, or like a study that you listing with clinical trials.gov. You can’t use it once a week, because it’s not approved once a week. You’d have to use it every day. But to follow this, it doesn’t work every day. So they would they’re like stuck because they can’t they have to they can’t just say we’re going to use it once a week. It’s like well, it’s not approved once a week, you have to prove it show is safe to once a week was loving the idea that was safe to give every day but as we said teams once a week that no that’s not to a higher dose once a week, you know, Western medicine you’d have you want to use it different than when it’s a food, you have to show that that’s a safe way to use it. I mean, if you’re doing a clinical trial, you want to have approved by the FDA, whatever, like mission trials with political stuff, you will have sir, like the
just institutional review board. So like if you can, okay. Like I say, well, well, that’s they can’t do that they can only side effects without clinical trial.
Robert Lufkin 34:08
Yeah, it’s sort of a catch 20 catch 22 well, so I have a
Alan Green 34:12
catch 22 and now they’re sort of like seven political positions they look at and say well, we see all these greats like affected like nice. Show us a human trial. Well, that guy like we don’t that we don’t we don’t work on like my studies. Show us that good human study, and then we’ll, they’ll be good. You will like to see that was done. Sophia said show in studio clinic, a human study. No one’s paid for it. No, it’s a study so it’s like it’s very difficult for people to like to use it. If they have a go to have a huge amount of experience use you get. Although a few people now are starting to say different places I’ve heard I’ve definitely been using
Robert Lufkin 34:57
for you. You have arguably the The world’s largest experience of clinical use for longevity, I think you mentioned you, you’ve just had over 700 patients now on rapid mice and that in your, in your private IP,
Alan Green 35:11
it’s like five years dimethylated, just like, you know, January 2016.
Robert Lufkin 35:17
And you specifically we, in your practice, the use is to pulse the dose to activate mtorr I’m sorry, to, to affect mtorr one, but not affect mTOR. Two, and that’s the whole purpose of that. And that’s,
Alan Green 35:33
that’s the whole purpose, I always use it just like no more frequent than once a week. Because once once a week is two and a half half lives, there’s like 55 hours. So if you take me up to like fairly low dose like six milligrams once a week, by two and a half half lives, by the end of the week, you have a low enough level this not getting into fields add to to play as far as like the other sort of like dose I’ve been experimented with. And this is suggested by bag a squared bag is clearly suggested 20 milligrams. And the I his idea of 20 milligrams was that that was the dose they used in cancer medicine, that was a well tolerated dose. And he is who he was concerned that it did place it might not be crossing the blood brain barrier enough anyway to like to have to have what was the of the blood brain barrier, he suggested a higher dose and have a higher dose to like gum. That’s what I’ll do now is up. Now this actually using it. Additionally, I would use it for about three years and six milligrams once a week. And then I have a couple of my patients, they were using at 10 milligrams and they had a very good response. And they test on their own. on their own. They said like you know, and they said, No, this is working great. So I would try that. So I had like I notice it went up to 10. And I still I get better, it’s felt that we sponsored that shows. So I stayed at that dose for like a year or so. And then for the last like four weeks, I’ve liked to I play milligrams every other week, like the idea of 20 milligrams. 20 milligrams is you’re like seems like a maximum dose. But two weeks is five half lives by attack glasses a theoretical like zero, like wherever you wherever it goes to start off with. By the time five half lives later, you should be at zero. So if you took 20 milligrams and you waited two weeks, you should be a zero by your new dose. So that’s just sort of like work out.
Robert Lufkin 37:48
Yeah, it’s just an N of one. But what have you noticed in going from six to 10 to 20? If anything in your personal experience
Alan Green 37:55
10 was better. And I 20 seemed better when entering
Robert Lufkin 38:01
in what way? Like what sort of what, what biomarkers or what did you feel?
Alan Green 38:07
I lost a few extra pounds on sir like 10. And I still like felt that. And I still like that boy, like they like notice it’s there. Like it’s sort of like it’s very subtle, but it’s sort of like I could say like No, I said yeah, this seems like, like a better dose. And it’s, it has a lot of side effects. And but you can sort of like notice the effects. You said, What’s going on? So I it seemed to me that like Yeah, I like that dose better. I like 20 milligrams every two weeks better.
Robert Lufkin 38:44
For your for your patients.
Alan Green 38:46
What are the web pages with my patients? Now? I haven’t tried them still answer like that. So I haven’t like gotten them still at once a week. And that’s still like the experimental sort of like stuff. And the following blog is slowly suggested on that. But I’m still think that most like like patients is still on like once a week. And mostly it’s led to weaken six no events. And last is a very dramatic problems. But as far as the wasted verbalizes remarkable through like also losing weight. It’s like the world’s greatest weight loss drug. And I mean, that’s the number one thing I feel like that measure is everybody is everybody’s home I i squat. What that stands for is homeostatic model of insulin resistance. So that’s a sort of like, it’s like insulin resistance, insulin sensitivity. Yes, the most important thing and being real healthy, and to make sure to get the message that you have to measure insulin, and then you measure fasting insulin and fasting glucose and you multiply the two together. That gives you your insulin resistance. Because that because the insulin is controlling the glucose, so the critical thing is, well, how much insulin Do you need to control to get this level of glucose. And so you won’t know what the insulin so you just multiply that together. And then you multiply together, you divide by 405, which is the magic number. And then you do that when it’s healthy. To come up with that number, so what is until is earliest resistance is three is significant for distance. But if you don’t want to do that, you know, there’s a very nice website, it says home is go up, and you just plug in glucose, plugin inside and push calculate, it comes up with your home is gone. So that’s something that well, every single doctor should always use, they should always measure insulin and glucose and calculate your home is good.
Robert Lufkin 41:03
Absolutely fasting insulin is such a powerful marker, why wait until your glucose becomes elevated, the fasting insulin can be can be elevated for 10 years before.
Alan Green 41:16
Right and the idea is that the hemoglobin a one see that you average blood sugar, so that so he shows when your blood sugar is failing, like a high level of insulin, and you’re controlling the blood sugar, you can have a perfectly good warm up, you could have perfectly good hemoglobin a one C. But your insulin insulin resistance hemoglobin a one C is that up until you’re basically now you’re failing to control your blood sugar. Now, it’s going up, but it’s a late Walker, but the hemoglobin a once the Homer II score, you can calculate that everybody. And it’s just extraordinarily effective. I mean, like they they people in fantastic shape. They’re like under one and healthy people around one peoples a little bit overweighted, too. And people fairly significantly tend to get into round three. So it’s like it’s a very, very heavy Stein’s very, very well.
Robert Lufkin 42:17
Yeah, yeah. That of your patients that are on the on the six or the 10 dose, what what are the most the most things they report both positive findings or side effects that you that you’ve seen in your practice?
Alan Green 42:33
Well, a typical report is it’s just a middle aged 55 year old women position. And she said, the cycling speed went from 15 miles now to 18 miles an hour. J so like, a good response. Like people so like notice that if they’re like, at maximum flooding at maximum cardiac output, so like cyclists, notice that the cyclists are always at maximum cardiac output sometime in the wake. But these are like when they’re cruising along, but like when they’re going up hills, or when they’re just like, they flat out as fast as they can go. Cyclists know exactly how they’re doing. They like yeah, they know exactly what’s going on. And then they have better cardiac function. They know it. And so cyclists are like, is that cyclists knows that they have better cardiac function. And, and other people sort of, like notice that if they are at a wheel, so like a strenuous activity, that’s the way it says they sort of, like do something that’s like, really, really challenging, and that they could usually do, and they notice it nicer, like getting short of breath to, to be able to do that better, like so forth to do something like you know, go on a big hike or do other stuff. But if you’re not sort of like doing very much, if you’re not challenging yourself, you don’t notice much of a change at all. It’s interesting. I mean, who is young, if you just if you’re not doing anything that requires you like maximal cardiac output, you know, I don’t like doing things that make you We’ll show the best you can do but different people might have different things can be if you’re you might, it might just be walking on a steep hill and I are supposed to sort of like you know, jackets or like tops like so but if you like you tend to tends to improve that the tests prove a thing called age associated quality of aptitude. That now that’s a sort of like thing, cardiologist never talked about the deaths, the number one thing that like, oh, the animals die from, like basically, that’s a universal thing in the animal world. I mean, they get cancer. So they get age associate quarterback apathy. And so it’s like a decrease in cardiac function with age. And that was to say that, like Matt Kapler was studied in a stock study in Seattle. And he was showing that we had like the middle aged dog, say gay rapper, bison. They improved their cardiac function. And he was showing that echocardiograms and Geico light day in the dinner, which they were like, it’s the same sort of like places like Seattle, they were showing they were doing the same studies on mice. And they showed a dramatic improvement in the mice. And why it is interesting, they show the same effect on either 40% to a restriction of approbation. And also like studies, they show the same kind of like, like improved cardiac function, but those guides went even further and they did a complete sodium then he would say, I printed out all the like, all the proteins in the heart muscle, and I sell my seminar to them, they can see which ones are up and which ones are down which ones change, which change with aging, which change of rapamycin, and they can see that they would have a reversal, but basically, it was a reversal of the mitochondrial function. And instead of like that burning function, and
it was the energy burning function, it was a shift from all that old plots were burning glucose, and young lights are burning fat. And a cancer like so is a shift. And basically, like the substrate that you were using, like they were using a better fuel is like yaguas use, burn fat in that show, like and it’s like with deterioration, they’re like shifting of the subject. That’s what sir, like, Jay like showing when they actually like, traced it down to what was going on. But they were both showing, like a marked improvement of cardiac function with so like that bicep, and that’s what I say to my patients, Mr. Like improvement of heart function. And they have like, they, they basically have to bid of their age way decline. Now, they say they’re not going like, if they were like, 25 it was a bad bit, but when they’re 50, they gain back some of what they’ve lost in like aging. That’s the sort of like what they’re doing. Ah, so that’s one thing people notice. And the other thing people notice is a lot less inflammation like aches and pains and sort of like joint pains and things like that. And people who have a like a, like degrees of mental fogginess, they notice that they’re working to do that and mentally more mental clarity right they feel that they do have a better mental function that’s sort of like the type of things people like notice people don’t notice that nothing that didn’t get any bad diseases that’s you don’t notice that he said I didn’t have a heart attack last week that he says that but people notice over like a couple of years that nothing bad happened to them and feeling pretty much the same not always there like I said typically science I feel the same this they get any better they get any worse they get a gay diseases they like feeling the same and feeling the same for like three or four years since like good.
Robert Lufkin 48:43
That’s a good thing. Yeah. What about what about untoward effects? Side Effects athletes ulcers what what what do you see
Alan Green 48:53
Michelle successor like like tend to be very mild but much more sir like serious and the transplant patients because transplant patients can never stop. But people like people you say ever get them actively taking a job for sir like six months, but in the first couple of months, so if they increase the dose, they’re likely to get them but they tend to be very, very small, like hardly like to say it’s not as much of a problem is something that you notice it’s like a pinpoint little area that you can tell you like you can fit like barely feel there’s some little thing and you’re slumped down that you can like feel inside likely to get this I mean, the size of an electrical signal. I think you can see we all sort of saw that some people get that but it’s usually not a problem because if it’s so like, you can simply start taking reclamation here I killed a couple days a week. So like you’ll feel fast when you start picking up a Mason. So it’s usually there’s not much of a platform. And there’s usually plenty of people can take things so there’s something called Olson swish which is So I could still go, I did a couple of other things that like will make it feel better. But that’s usually not much of a problem for the transplant patients, because this they can do on a higher tenuous dose, and they can stop, and they get laid off, but still is unclear, but it is, I think it’s an M to one effect. Now, the way I think that desyrel, like the M tau one, I think it’s basically a disease of unknown poised. But I think what’s happening is that no one is stopping the proliferation of cells in the slows down the restoration of some group of waking coastal cells, then you have a little spot relating to like that, like we share that. I think that’s going on. But I think over the fact that just happens in beginning and overthrow time, I think the stem cells doing that, they’d get a better function. So I think but i think i think it’s just a stem cell function. And I think I said mTOR, one function, I think the mTOR one initially is slowing down the function of the stem cells, the dead is sort of like afterwards going on for a period of time you take it, now you have a better function of stem cells, because now you’re not getting the topic because it’s just happening early. But it’s not. But it’s much more of a trivial kind of thing. So the main sort of like, serious problem is, the decreases is that a direct effect of M to one that decreases your innate immune system. Now your innate immune system, that’s decreasing chronic inflammation, that’s generally good for most h laden things. But it’s not good. If you have a bacterial infection, that innate immune system is sure. Number one defense against bacterial infections. So when you’re taking that your resistance to bacterial infections is definitely decreased. I mean, I saw like one study in which they had mice on coolock restriction. And they supposed to say like a bird. Now, they were much more likely to die, because they were like that, and floppy sticks in it’s depressing their innate immune system. So that would probably be a problem. If it wasn’t for the fact that we have like a new generic drug called antibiotics. So it turns out that like, with evaporation, it actually makes you a lot better off fighting a bacterial infection, then nobody buys it and no antibiotics. So as long as people have had access to antibiotics, anything that’s suspicious for bacterial infection, if you take antibiotics, it clears up within a couple hours. I just like a neat because up, so it’s, but if you did not have a few sir, while retaining that information, and you didn’t take antibiotics, and you had a cough, and you didn’t take out, you kept on going, and you just figured, well, I that cost before they get better, you could wind up in the hospital. So it’s really important to figure that you’re welcome. I said, your native immune system, fighting a bacterial infection is decrease. If you have a thing, like a cough, that could be a bacterial infection, you should take an antibiotic like this remixing. And then whatever, you have thoughts of bacterial infection to clear up to death.
I would say that’s the main sort of like thing, as far as the other type of side of things, is, is a transient increase in lipids. But that’s not sort of like is that’s not a dangerous effect does was usually if your LDL and so forth and up, it would seem like you’ve had an increase this, but if we optimized it, you’re not going to increase this because you’re decreasing the levels are leaving the tissue supposed to enter the tissues is decreasing, the ability to enter is decreasing due likability oxidized as decreasing inflammation. So they did various like studies, it’s like polio disease as their sclerosis, it didn’t matter that they had like the adults could have real high cholesterol levels, the cholesterol still leaving the tissues, and the lesions were clearing up to recently clearing up the guys about the blood level. So so if I grab the mice in the blood level, that would be dangerous, if you were about basic is much less dangerous if you take that with my son, but people always sort of like just stare into it. If it’s sort of like at this like elevate, as you said, that effect tends to be changing. So I’d say that’s not too much of a joke. For the most split, it might, it has the effect on insulin to like, lower insulin. And the idea is like the balance that you’re supposed to like, lower inside and improve your insulin sensitivity and like lose weight. If you simply lower insulin and you didn’t do anything to get insulin sensitivity, you’re against, like, glucose could go up a little bit. But for the most part, it’s happy people, the net effect for most people is improving your insulin sensitivity, because like, your insulin is going down, and insulin resistance is going down. And so you want to have those two effects, though insulin improve insulin sensitivity. But so then you want to have that. But it’s a, it’s an extraordinarily good, you’re preventing diabetes, because type two diabetes, because it’s a very good drug for losing weight. People like to lose like, mice and people can lose, like, the extra weight and become insulin sensitive, and totally reverse insulin resistance in a type two diabetes.
Robert Lufkin 56:15
Yeah, this is a fascinating experience you have, if it’s alright with you, this, this has been so useful and so fascinating. I’d love to invite you, I’d love to take the Sat Nav discussion in this analytics. And if it’s all right with you, I’d like to invite you back again to spend a whole segment on central Linux if that’s okay, that’d be great. And, and, and this time, before we go today, just you already mentioned your your current regimen of rapamycin, and and then we’ll talk about the analytics I guess next time do you can you share with us any of your choices about diet, any particular fasting that you do, or any exercise or other lifestyle things that you do? Well,
Alan Green 57:09
I suppose like exercise, I like to just people like get it out of walking three or four times a week. I think that’s still like very, very important. As far as the number one thing I think people should do is they need like a tape measure and measure the waistline. If you’re, if you’re five foot 10 and seven inches tall, your waistline should not be over half the height, your waist size should be 35 inches. So I think that’s the only sort of like diagnostic test you need is a tape measure. And sliced in the diet do any fast. I think fasting is good because it was like enter. So like, but as far as like diet, the diet that I like to try beyond that I’d recommend is alone with tiny diet. It turns out that like the thyroid is a very strange amino acid, it’s code on one to every amino for every protein made by every sterile like, like, you can’t ever see that in the nucleus. So every time they make a protein, position number one is a tiny. So if you buy a flow of assigning it thinks well I better not be like it says the same squat restriction. Well, you might be tearing things down or they are tiny. And the tiny is so low this tiny diet is pretty much a vegan diet. It’s like nothing was designed you decide like fish and chicken and beef and eggs, but low and most vegetables. So like I was so like, he like basically vegan diet you eating a lot of the time diet deaths are like very similar to a floppy sticks. But I see Oh, that’s that’s great. Yeah, yeah, they had they just started to like, that’s bad, bad 7.2 cent lawyer flowing up, and just Aloma tiny die. She’s actually sort of a thing I like about diet. And also I like a diet that’s like, Whoa, and what hell is this era called Advanced glycation end products. They’re the things you sort of like get when you like cooked meats at a high temperature and I grilling and flying and so forth into things that get foods taste great.
Robert Lufkin 59:32
That’s right. It’s a balance. Yeah, well that that that’s great. Thank you. Thank you so much Alan for spending time with us and and I I’m really looking forward to our next session when we when we talk about cinematics and the great work you’re doing there but I just want to thank you for your time today and sharing the the beautiful things you’re doing.
Alan Green 59:58
The thing I say like no The chatty squeezely about San Antonio, Texas is now treating people with early Alzheimer’s disease. And I MCI, say late this afternoon. And I expect based on this, so like this day, they mentioned, I expect them to get very, very good results in that. And as soon as people start the treatment, the data.
Robert Lufkin 1:00:20
Great, great. All right. Well, thank thank thank you again for taking the time to be on the program. And look forward to speaking with you again soon.
Alan Green 1:00:31
If I put one last thing, sure, basically go to 23andme. And get genetic testing done.
Robert Lufkin 1:00:38
What snips in particular to look for,
Alan Green 1:00:41
everyone needs to know, if the average gene for a P e. for 22 cents, the Hebrew e4 applies to 50% of the cases about 10 disease, there are three times more likely that 10 times 10 years your mindset. That’s the people who still like this, people have to know that this says they can take proactive steps to prevent it because it’s very preventable. If you know you have this.
Robert Lufkin 1:01:09
Great, I love that and we’ll link to 23andme. And also, we’ll put the links to the snips in there. So if people want to do their own searches on after they download their data, we’ll show them how to do that as well. Okay, great. Thanks again, Alan, it was great talking with you. Okay, bye.
Unknown Speaker 1:01:31
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