134-Top Podcast of 2023

Got a minute to ponder the fleeting beauty of life and the tantalizing possibility of extending our time here? Come on a journey with us, as we reflect on gratitude, transience, and the magic of potential longevity drugs. In our year-end episode, we're revisiting one of our most engaging topics from the past year - the promising molecules of Rapamycin and Metformin. 

Have you ever wondered what would happen if we could use modern medicine to extend our lives? We're taking a deep look at two fascinating drugs that might just make this sci-fi concept a reality. We'll walk you through the ins and outs of these potential longevity gems, discussing their mechanism of action, available evidence of their lifespan lengthening effects, their rich histories, and important safety considerations. You'll get a glimpse of the intriguing study that sparked interest in Metformin's potential for longevity and the ongoing debates surrounding these potential life-extending drugs.

But we're not stopping there. We'll guide you through an exploration of Metformin, commonly used for type 2 diabetes, and its potential to reduce all-cause mortality, cancer, cardiovascular disease, and neurodegeneration. Rapamycin also gets its fair share of the spotlight, revealing promising anti-aging effects in animal studies and potential benefits for diseases of aging. 

As we cap off another year, join us in appreciating the present moment, expressing gratitude for each day, and contemplating the exciting possibilities that the future of longevity research holds.

ReverseAgingRevolution Summit June 20-22, 2024 https://robertlufkinmdcom.ontralink.com/t?orid=49&opid=2

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Transcript

Speaker 1: 0:02

Welcome to the Health Ungevity Secret Show, and I'm your host, dr Robert Lufkin. This is actually the very last podcast of this program for 2023. And it's become a tradition that here on this last episode, we use it to replay the most popular podcast for the entire year from our program, and we're about to do that. But before we do, I just wanted to take a moment to talk about gratitude. In this holiday season, one of the most reliable ways for me to find gratitude in myself is to examine the world through the lens of transience, and I'm about to play a short piece from the great Sam Harris about how he thinks about the transient nature of our world. Sam, as you know, has an amazing podcast which I highly recommend, as well as a wonderful app called Waking Up for Mindfulness with Daily Meditations, but please now enjoy his thoughts on the subject.

Speaker 2: 1:26

I'd like you to take a moment to think about all the things in this life that you will experience for the last time. Of course, there will come a day when you will die and then everything will have been done for the last time. But long before you die, you will cease to have certain experiences, experiences that you surely take for granted now. If you're a parent, when is the last time you will pick up your child or tuck her into bed or read her a story? Our youngest daughter still says Aminals instead of Animals, and though I'm a stickler for words, I am not correcting her. Each one of those is priceless. Now, thinking in this way lends a poignancy to everything, even to things that you don't like. Again, let's say you're a new parent and you're getting woken up several times a night by your baby. That's brutal, but there will be a last time, and knowing that can change your experience in the moment. There's something sweet even about this experience. It's possible that you will miss this. We do everything a finite number of times, and yet we tend to take even beautiful moments for granted, and the rest of the time we're just trying to get through stuff. You're just trying to get to the end of whatever experience you're having.

Speaker 2: 2:58

Tim Urban, who writes this wonderful blog titled Wait, but why? Often touches this topic. He actually publishes a poster which represents 90 years of life in weeks. Each line has 52 squares and there are 90 lines on a single page, and the scale is frankly a little alarming to contemplate. Each week is a significant piece of 90 years, and you can put your finger on the current week in your life. You can see where you are, and then, of course, you realize you have no assurance of how many weeks you have left. Assuming that you have 90 years certainly 90 good years is generally not a safe assumption.

Speaker 2: 3:44

What you can know, however, is that each time you do something, pleasant or unpleasant, that is one last time. You will do it, and there will come a time when you will have done something the final time, and you will rarely know when that is. For instance, I used to love to ski and I now haven't skied in well over a decade. Will I ever ski again? I have no idea, but I can assure you that the last time I took off my skis, I was not even dimly aware of the possibility that it might be the last time, right, that I might live for many, many more years, and yet this stood a good chance of being the last time I would ever ski. When is the last time you swam in the ocean or went camping? When is the last time you took a walk? Just to take a walk?

Speaker 2: 4:38

As you go about your day today, consider everything you're doing is like this Everything represents a finite opportunity to savor your life. On some level, everything is precious, and if it doesn't seem that way, I think you'll find that paying more attention can make it seem that way. Attention really is your true source of wealth, even more than time, right, because you can waste time being distracted. So this is just to urge you to take a little more care. When you meet someone for the first time and you shake their hand, pay a little more attention. When you thank somebody for something, mean it a little more. Connect with your life, and mindfulness is the tool that allows you to do that, because the only alternative is to be lost in thought. And every time you notice that you're lost, that you're distracted by a thought about the past or the future, and you come back, you are training your mind, and it may feel like an effort at first, but eventually it's like continually waking up from a dream and ask yourself how much effort does that take?

Speaker 1: 6:14

I'm personally grateful for many things in my life, including, but not limited to this one.

Speaker 4: 6:24

Oh my goodness, oh my goodness.

Speaker 1: 6:33

And now drumroll without further ado. Please enjoy a replay of the most popular podcast for the entire year of 2023 on this program, which was presented on April 10th 2023. We revisit the topics of rapamycin and metformin and longevity and hopefully, if you haven't heard it already, you'll find it very interesting. Please enjoy. This week we'll be covering two of the most promising longevity drugs known rapamycin and metformin. In fact, we get more questions about these drugs than any other longevity drugs on the program and, while many of the answers are still not known, there's no shortage of questions. So what I'll be showing today is a presentation I gave at the A4M conference in Las Vegas just a few weeks ago, in December. It's a wonderful program.

Speaker 1: 7:38

I'm actually going to be presenting at the A4M upcoming conference in Orlando, florida, in May, where I'll be keynoting there. Steve Sideroff will also be presenting there and also Steve and I will be giving a day-long workshop on longevity at the upcoming December 2023 meeting in Las Vegas of the A4M as well the December meeting that you're about to see. It was great to have an in-person meeting. Finally, the meeting was a blast. There were over 6,000 attendees and such great speakers. I had so much fun with my presentation we had almost 3,000 people in the audience. You could really feel the energy in the room. Anyway, here we go.

Speaker 3: 8:39

Please join us in giving a warm welcome to Dr Robert Lufkin. Dr Lufkin is a chief of metabolic imaging and a clinical professor of radiology, with an academic focus on the applied science of longevity. In addition to being a practicing physician, dr Lufkin has served as full professor at both the UCLA David Geffen School of Medicine and the USC Keck School of Medicine. Among his many inventions, including several patents in artificial intelligence, he has developed an MR-compatible biopsy needle which is used worldwide today, known as the Lufkin needle. Dr Lufkin has given lectures and keynotes around the world, and his latest book Lies I Taught in Medical School has just been published. Dr Lufkin's vision is to reimagine the conventional healthcare model with evidence-based, clinically proven lifestyle modifications and other tools to improve health and longevity by preventing and even reversing the most disruptive diseases and chronic conditions. Welcome to this stage, dr Lufkin, hey everybody.

Speaker 1: 9:57

What a great time to be interested in longevity and anti-aging. Our knowledge of longevity science has exploded in the last few years like never before, as evidenced by the cutting-edge research that's coming out practically every day and organizations like A4M and this remarkable conference, but most of all, all of you with your interest in this space. For the very first time, it's now possible to actually begin to suggest potential, credible drugs that produce anti-aging, and that's exactly what I'm going to talk about today. When I discuss two of arguably the most promising anti-aging drugs that have ever been known, and those are Metformin and Rapamycin. I'm going to cover both the evidence for and the evidence against it, and we can all decide at the end. But before I do, I've been asked to make a couple of disclosures here. First of all, I am a medical doctor. I am a practicing physician, so what I'm about to tell you should not be taken as medical advice. Rather, it's for information purposes only educational purposes, really. Secondly, what I'm about to tell you is my own opinion, as best I see it, as I read the literature, and it is not the official opinion of the UCLA School of Medicine or the USC Keck School of Medicine, where either I am, or have been, a full professor on their medical faculty. Finally, financial disclosures Rapamycin and Metformin are only available by prescription, under a doctor's guidance. I make no money from the sale of Rapamycin or Metformin or any related products. I do teach courses in longevity and anti-aging, both in formats like this and on my website, where I do mention Rapamycin and Metformin the learning objectives. We're going to look at these two fascinating molecules and they really are fascinating. We're going to talk about the mechanism of action. Then we're going to look at the evidence for their longevity effects. Every time I make a statement most every time I will include a referenced article for that not USA Today or something, but actually a peer-reviewed scientific article. You can go in and look at the facts there and read the evidence for yourself. Then, finally, we're going to look at both the evidence for and the evidence against these amazing medicines, and then we can all make up our minds when we decide.

Speaker 1: 13:16

Metformin and Rapamycin have a number of similarities. They're both naturally occurring. They're not made in any laboratory. Metformin is from the French lilac and it's been around for thousands of years with medical applications. Rapamycin, on the other hand, is from a magical bacterium that wasn't discovered until the later half of the 20th century. They both occur in nature.

Speaker 1: 13:49

They were both interestingly approved by the FDA, the Food and Drug Administration, for human use for certain indications in the 1990s. And FDA approval means that they have to meet a certain bar as far as safety and they have to be useful in humans, at least for these certain indications, and we'll talk more about that later. Patient status or patent status rather, both of these are off patents as far as drugs there are, which means there are generic forms available. That's both good and bad news. The good news means that they're inexpensive. In their generic form, both rapamycin and metformin are relatively inexpensive. The bad news is that, without having an intellectual property like a patent, it discourages drug companies from spending a lot of money to develop new applications or new FDA approvals for them.

Speaker 1: 14:49

They both have a huge history of human use in the last, really the last 20 years. It's been stated that metformin there are 150 million doses of metformin used every single day and the last thing about these drugs. Another similarity is they both had kind of surprising, unexpected anti-aging or longevity effects, and we'll talk about those. They have several differences also In human usage. Metformin is used for, typically, diabetes, and it's been used for thousands of years. Like I said, rapamycin has only been used in the last 20 years for in humans.

Speaker 1: 15:38

Drug specificity is very different between these two drugs. Metformin is what's known as a dirty drug, and we'll talk about that. In other words, the mechanism of action is not really well known. There's many, many different network effects and there's a lot of confusion and not even agreement about how metformin works. Rapamycin, on the other hand, is what's called a clean drug. It has one target, one effect, and it's very, very specific. The longevity results, as we'll talk about, are very different. Also, and finally, the safety profile of these drugs is different, and this is a constantly evolving factor.

Speaker 1: 16:23

We'll look at some evidence from papers that just came out a few weeks ago in this. So let's start with metformin. Metformin is the oldest drug. As I mentioned, it's been around. There's evidence in Egyptian documents thousands of years ago where it was used. It's from the French lilac. But its modern medical use really happened in the end of the 20th century, in 1995, with FDA approval. You can see from the graph here that, starting in 2000, the papers these are scientific papers about metformin have just exploded. So this is really a 21st century drug, although it's been in use for thousands of years. This is a study that really blew everyone's mind about longevity and this started the whole longevity question with metformin.

Speaker 1: 17:16

Metformin was originally a drug for type two diabetics. It lowers the glucose in these patients and it's very powerful. It's a mainline drug for it. The other drug that was being used before metformin was something called sulfanolureas, and the problem with the sulfanolureas is they were associated with increased heart attacks and cardiovascular disease, which diabetics get to. So someone wanted to do a study and they did a very large study of over 180,000 people. They looked at and this is a survival curve. Essentially, this is time to death, this is relative survival and these are normals that they put in there sort of match normals, and these are diabetic patients on sulfanolureas and you can see that in any given point in time they're fewer and fewer diabetics alive. So this is a curve now showing the death rate of sulfanolureas versus normal patients without diabetes, versus the sulfanolureas with diabetes. So what they did was then they took a group of patients. Instead of giving them sulfanolureas, these type two diabetics were given metformin and they did the same study. They looked at survival with metformin and what they found was this green curve is a metformin. Something very interesting happened that the type two diabetics treated with metformin. They not only lived longer than the sulfanolurea patients, but they lived longer than normal patients who didn't even have diabetes. Let me repeat that Type two diabetics treated with metformin lived longer than normal people who weren't taking metformin, who didn't have diabetes. So this began a whole inquiry into longevity effects about metformin.

Speaker 1: 19:09

There are a lot of unanswered questions, but certainly something is going on here. Well, first of all, the mechanism of action of metformin. As I said, this is metformin is a dirty drug. There are many, many mechanisms. It enters the cell here. It affects the mitochondria, it blocks certain actions in the mitochondria, it raises something called, it affects AMP kinase and it blocks MTOR here. Some of these names may be familiar to you and we'll be talking about them later on. But there's many, many different actions within the cell and in fact a recent article just came out that people are saying metformin mechanism action may not be all of those, but it may be primarily related to gut bacteria. In fact, these are CT PET scans of the abdomen and the black means glucose activity and these are patients and the black is glucose in the bowel loops when they're given metformin. And these are patients without metformin. So metformin dramatically not only does all these other things to the microbiome and AMP kinase and MTOR, but it also changes the gut microbiome in there. So the short answer is we really don't know how metformin works. But that's okay, let's investigate this.

Speaker 1: 20:39

Let's look at this difference on this graph and this is what's called all-cause mortality. In other words, people diabetics taking metformin died less frequently than normal patients not taking metformin. And what did they die of? They died of all-cause mortality, which we can is known. People die of certain things, most likely heart disease and stroke, cancer and neurodegenerative diseases like Alzheimer's disease. Let's look at each one of those and see what effect, if any, metformin has on these. Well, here is a study of cancer patients who were given metformin, but these are actually type two diabetic patients. We have a lot of those that are taking metformin and for certain types of gastrointestinal cancers, when they started taking at least 500 milligrams of metformin per day, their cancer rate dramatically dropped. So there is evidence that in diabetics, metformin reduces cancer. Doesn't say anything about non-diabetics and that's the big question, but at least it does have some effect on cancer, a positive effect on cancer.

Speaker 1: 21:56

What about cardiovascular disease in metformin? This is a huge study of almost a million patients, a meta-analysis of 40 different studies, and they found that metformin also reduces cardiovascular mortality and all-cause mortality in these patients. But the problem was for patients without type two diabetes, metformin has no significant effects on the cardiovascular events. So again, it's still this sort of muddied picture. If you have type two diabetes, metformin is gonna help your risk of certain cancers and also cardiovascular disease, but as far as normals, we don't have that data yet. If you don't have type two diabetes, what is metformin gonna do for you? We don't have that data yet.

Speaker 1: 22:45

The last big killer in all-cause mortality for all of us that we're facing is neurodegeneration, specifically Alzheimer's disease. And this is a study of patients with type two diabetes again, because that's the only group we have large numbers for with metformin. And what we see is this meta-analysis of 28 different studies metformin therapy decreased the risk of cognitive decline in patients with diabetes. So here's the baseline you give them metformin, their risk of cognitive decline decreases. The problem is, or the kicker here the use of metformin by the adults with diabetes did not reduce the risk of Alzheimer's disease. So again, it's kind of a mixed message there.

Speaker 1: 23:35

How about longevity in metformin, as we're gonna talk about later? Longevity is very, very difficult to assess in humans or even animals. But I'll just summarize the data here. In the nematode worm, the standard model for longevity, metformin works. The results are very positive. In mice, as we'll see, the results are mixed. Sometimes it works, sometimes it doesn't work, and humans we really don't know. Biological clocks you may be familiar with DNA methylation clocks or pheno-age clocks. These are some of the standard Horvath or HANEM DNA methylation epigenetic clocks that show your biological age versus your chronological age, and patients taking metformin were able to reduce their biological age as measured on these clocks and also the pheno-age clock from Morgan Levine there. So there is some evidence that at least these biomarkers of aging are decreasing.

Speaker 1: 24:45

There are some risks with metformin. One of the big ones that people talk about is bodybuilders don't wanna take metformin because at least there's some evidence that it decreases the ability of the body to put on muscle and we'll see in aging that's one of the problems If people lose muscle as they get older in sarcopenia. So here's one risk of metformin. And this is still very recent. This is 2019. The data is still being sorted out, but some bodybuilders take metformin for a couple of days and stop it when they work out. But I just wanna point out this is a risk.

Speaker 1: 25:25

Here's one other risk that just came out a few weeks ago. This is a study this year of over a million patients and they showed an association between paternal metformin treatment and increased numbers of genital birth defects in males and a tendency towards a skewed sex ratio. Now the problem is you can say, well, maybe I'm past the reproductive age, I'm interested in longevity, I've already had my family, I'll just take metformin. Who cares? Or I'm not taking metformin at all, it doesn't matter. Well, actually it matters to all of us because metformin, unlike most or many biological substances which are degraded in our metabolism, metformin essentially passes through unchanged and it is excreted into the water supply and into all our systems. So the general population may be being exposed to metformin. So things like birth defect risks and all are gonna require a little bit of attention.

Speaker 1: 26:34

But again, this is one paper from 2022. This is breaking news. It remains to be seen what the impact this is gonna be. When are we going to get answers about metformin? This is the TAME trial. It's a great study from near Barzali that he's put together. It's a six-year study of 14 institutions and they're going to look at 3,000 individuals over six years and they're going to basically give them metformin versus a control and look at markers of aging, chronic disease, heart disease, cancer and dementia. So once this study gets rolling, we should know very shortly at least the results from this study.

Speaker 1: 27:16

So in summary, metformin first of all, it's a dirty drug. Nobody really agrees on the mechanism of action. There's a huge use in diabetics 150 million patients a day and it has been shown that in these diabetics it lowers the all-course-cause mortality beyond that of even normal people who aren't diabetics and aren't taking metformin. It's value in non-diabetics Not sure, you know, stay tuned. Longevity effects Same answer, not sure, stay tuned. Safety we talked about the muscle, and then the recent question about birth defects, but these are happening right now, so hopefully we'll know more a year from now. So that's metformin.

Speaker 1: 28:10

If you like metformin, you're going to love rapamycin. This rapamycin is a magical drug that was discovered in the 1960s on a beautiful, remote tropical island that was thousands of miles away, completely isolated from the largest land mass, and because of that. Scientists suspected that there would be unique organisms living there, at least in the soil and that sort of thing, just because they hadn't been exposed to other organisms around the planet because of this isolation. Well, in 1962, this was all about to change when the people on the island decided to put in their first airport, which meant that a lot of people were going to be coming in. So, in order to not miss this opportunity of all these possible organisms, scientists went there by boat and they harvested a bunch of soil and took the soil samples home and then analyzed them, and they were not disappointed. They found a number of unique organisms that were not known before, but by far the most significant organism they found was a bacterial species that produced a compound that they named after the island, which the island is Rapa Nui, and they named this drug Rapa Mycin.

Speaker 1: 29:33

This drug has amazing properties that they just began to see. They first thought it would be an antifungal, which it is, but it also slows cancer, it has effects on atherosclerosis, it has effects on immune function. It has amazing effects. But as amazing as these effects were, perhaps the most significant thing that Rapa Mycin did was it allowed us to discover, arguably the single most important molecule in all of biology, the single most important protein. It's a signaling protein that was named Tor as target of Rapa Mycin, for lack of a better name. This molecule is conserved in all animal species, from yeast all the way to humans, and it's fundamental in what it does for the cell. It does one thing for the cell and that allows the cell to survive.

Speaker 1: 30:34

Tor acts like a switch in all of us. Tor switches either. It does two things. It detects the presence of nutrients. Either nutrients are there or they're not there. If nutrients are there, tor switches to this mode, which is growth mode and inflammation. But this is very important. If nutrients are not there, tor switches back to repair mode, which is also important, if you think about it, for a cell. The most important thing for a cell to do is survive, and Tor tells the cell how to survive. In other words, if nutrients aren't there and the cell switches to growth mode, the cell will die. If nutrients are there and the cell switches to non-growth mode, it will miss an opportunity and not be optimized for its environment.

Speaker 1: 31:25

Now, human beings switch between growth and repair mode based on the presence of nutrients, which is largely reflected by our diet, to some extent by oxygen as well. Cell humans over the millennia. This switches back and forth, at least it's believed to do that. Modern humans, though, because of the abundance of food, and junk food in particular, and carbohydrates in particular, which this is, glucose sensing are basically sticking the Tor switch into growth mode for all of us. We're eating all day long, all night long, until we go to bed, and then we wake up first in the morning and eat breakfast, and so this has the effect of turning Tor on.

Speaker 1: 32:08

Two of the most compelling arguments for a mechanism of longevity are, first of all, the wear and tear hypothesis that many people subscribe to is that is, we just wear out. That's what aging is we wear out, we fail to repair things. The other new idea from Misha Blaglaskoni and others is about hyperfunction, where aging is really an antagonistic, pleotrophic effect of genes that were good when we're young and cause us to grow, but when those growth genes are turned on in old age, they create atherosclerosis and cancer and this sort of thing. But the great thing about M-Tor is the M-Tor hypothesis for longevity is that if you turn M-Tor down, you will turn up repair, which repairs things, and you'll also turn off growth, which so it works for either model of longevity. And, of course, what does Rappomycin do? Rappomycin turns M-Tor off. So here's a drug that's specifically targeted to turn M-Tor off. Well now, if M-Tor does these things, then an M-Tor is the fundamental driver of longevity and aging. We should see effects of Rappomycin.

Speaker 1: 33:24

So let's take a look at some of these. So let's start with the phenotypes of aging. We can all agree on this, right Gray hair, wrinkles, baldness, hearing loss these are all things phenotypes of aging. So here's some animal models of hair loss. These are baldness rats that when they're given control here the hair does not grow. When they're given Rappomycin, you can see the hair follicles are present here, that the hair regrows versus the control. Here An interesting thing also happens. This is days post-treatment. This is Rappomycin, this is the control. The pigmentation changes, so the pigmentation increases, so it's sort of a reversal of gray hair also. So those are hair changes, those are mice.

Speaker 1: 34:11

Let's look at another phenotype wrinkles, and this is actually a study done in humans. These were elderly people who rubbed on Rappomycin cream versus the control on their hand once a day for eight months, and then these brave souls agreed to punch biopsies of their hands to actually get histological specimens. And you can see, this is the control here and this is Rappomycin. You can see dramatic. This layer seven, collagen is reforming, which is a marker for youthfulness and less wrinkles and improvement, and in fact, in 2022, just a few months ago, the FDA approved the first topical version of Rappomycin as a Rappomycin cream. Now, to be clear, the indication is not for wrinkles in old age, it's for another medical condition. But certainly we're probably going to see a lot of off-label use for these skin changes.

Speaker 1: 35:09

So, no matter how many Led Zeppelin concerts you happen to avoid growing up, you're still going to be facing hearing loss as you get older. 30% of 50-year-olds have hearing loss. 60% of 70-year-olds have age-related hearing loss and it's part of aging. This is an animal model for hearing loss where mice were either given control or Rappomycin and we're looking at the organ in the mouse that runs hearing. Essentially it's the cochlea and it's hair cells in the cochlea and what we're seeing here is the animals who got Rappomycin had less hair cell loss. The hair allows us to hear better and with hair cell loss you have hearing loss. So we see less hair cell loss with Rappomycin and also there's some markers for improved hearing as well in this animal study.

Speaker 1: 36:08

Only half of people in the world get this disease of aging, but if they live long enough, 100% of them get it. It's ovarian failure, or better known as menopause, and this is a disease of aging, right? And if rapamycin works at some fundamental level of aging and longevity, it should affect this too, right? So this is an animal study, with rapamycin given in the red versus controls here, and this is number of pups per litter in mice and basically what it shows is increased fertility delay menopause in the animal model. And I should say that all these animal studies that we're seeing now there are human trials underway that haven't been published, but hopefully a year from now we can talk about the human studies, but this is an area of active research for rapamycin, for all these things.

Speaker 1: 37:03

Now you're probably saying wait a minute. Nobody dies of menopause, nobody dies of gray hair, nobody dies of baldness. How can this drive longevity? So to look at longevity effects of rapamycin, we need to look at the diseases of longevity, because these are the diseases that determine longevity. It's not gray hair, it's not hearing loss. When they die, they die of heart disease or stroke or cancer. When we die, we all die of these things. So let's look at these.

Speaker 1: 37:32

Cardiovascular disease is the number one killer. It's narrowing of the blood vessels Over time. The blood vessels transmit oxygen to the cell, to the cells, and if the blood vessel to the heart narrows, you get a heart attack. If the blood vessel to the brain narrows, you get a stroke. There have been tools to improve these. One is to expand the blood vessel with something called a stent and mechanically expand it, and it's been shown that the problem is the disease reaccumulates in these stents and they clawed off again. But rapamycin has been FDA approved and shown as an indication to slow atherosclerosis. When these stents are coated with rapamycin, atherosclerosis decreases Cancer. There are eight indications, fda approved indications for rapamycin use for cancer, all the way from treating metastatic renal cell carcinoma, which is the number one kidney cancer, to things like bone marrow cancers as well. So the evidence in cancer is there as well.

Speaker 1: 38:40

For Alzheimer's disease, there is no pharmaceutical manipulation that we've come up with. It's the ultimate failure of our medical system. But in the animal model at least, these are the normal mice here. These are Alzheimer's mice and this is a memory test. By giving these mice rapamycin, they're able to return their memory to the baseline levels. And, as I said, human trials are underway at the University of Texas in this for Alzheimer's disease patients in rapamycin.

Speaker 1: 39:11

Longevity itself well, these are diseases of aging. What about longevity itself, in other words the length of time we live? And humans? We really can't measure that for logistical reasons. But this is the gold standard.

Speaker 1: 39:26

It's called the Interventions Testing Program. It's a study run by our government where they get a bunch of mice. Mice are great because they only live three years. So they take the mice and they divide them into two groups and they give one mouse a nutrient supplement, a drug, and the other group of mice they just let them go and then they compare survival versus time. And if there's a difference between the untreated and the treated mice then there is an advantage to that drug.

Speaker 1: 39:54

And the other great thing about this program is you can suggest things like resveratrol. You can suggest things and have people test it. So resveratrol, nicotinamide, riboside, ashwagandha, green tea extract, even metformin All these things have been tested in this program and guess what? None of them worked. The problem just because a caveat here just because they didn't work doesn't mean they don't work at any dose, but that the doses tested they didn't work. So remains to be seen.

Speaker 1: 40:24

Did anything work? Well, yeah, aspirin worked a little bit. Something called acarbose worked Pretty good amount there. This worked in males, not in females. This worked in males, not in females. Is there any drug that consistently worked in males and females at all? Virtually all doses tested reliably and dramatically increased longevity and lifespan. Yes, rapamycin at the ITP and this just shows a study it not only works when it's given in the entire lifespan of the animal. In this case, rapamycin, for logistical reasons, wasn't being able to be given to the mouse until the mouse was about 2 thirds of the way their life, like 60 or 70 years old, and you still get the dramatic effects of rapamycin. So rapamycin isn't a drug that you have to take all your life to get these longevity effects. Risk for rapamycin there have been a few things immune suppression but this is a study at the doses people use for longevity and it's a very different dose than people use for organ suppression. There is actually immune enhancement with rapamycin, so it's good news with that.

Speaker 1: 41:37

The same question about net foreman with sarcopenia, muscle wasting with rapamycin, has been asked. You're turning down growth. I want to grow and build muscles. Well, actually, in elderly patients, rapamycin increases muscle growth, so it has just the opposite effect. And then, finally, with the new work in psychedelics and BDNF and brain-derived neurotrophic factor, the mechanism of these psychedelics is working by brain growth. You don't want to give rapamycin to minimize the effects of your ketamine or your LSD or your psilocybin, but what they found is that, paradoxically, net foreman I mean rapamycin actually increases the effects of ketamine on depression. Six milligrams given two hours before your ketamine psychedelic experience, and it dramatically amplifies that. So I guess the question of the hour is well, first of all, you can go out on the strip and you can buy metformin or rapamycin at any Walgreens or CVS or any pharmacy there.

Speaker 1: 42:44

So should we take metformin or rapamycin for longevity? And the answer is wait. I can't tell you that would be medical advice, sorry, no, seriously, the answer is we really don't know. It's complicated. We really don't understand longevity. We don't understand how these drugs work.

Speaker 1: 43:07

There are effects with lifestyle that are going to be very important. It's not enough just to take rapamycin. You're probably going to have to fast and stay off carbs. Here's metformin. There are synergistic effects with drugs. Here's metformin. It doesn't work on the ITP, but when you combine metformin with rapamycin, you get a bigger effect than rapamycin alone, and this was 2016. And late breaking news a few weeks ago, people combined and published rapamycin plus acarbose that other drug and you get almost a 30% improvement in lifespan. This is on the ITP, again by combining rapamycin plus acarbose. Acarbose is another diabetes drug. So there are a lot of unanswered questions in all these things. But, like we said, longevity research is exploding like never before. With A4M and meetings like this, it's a great time to be in this space. The future is very bright and I think the best is yet to come. Thank you very much for your attention. Thank you.

Speaker 4: 44:39

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