Longevity and mTOR: What the Science Says, with Dr. Robert Lufkin

Turning on MTOR all the time like we're seeing not only drives the phenotypes of aging, wrinkles, gray hair, hearing loss, menopause, but it also drives chronic diseases, obesity, hypertension, diabetes, cancer, and Alzheimer's disease.

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Hello and welcome to the Feel Freaking Amazing podcast. I'm Wendy Trubo. This is Ed Levitan. I said to him before the show started that it was like a rare animal sighting in the wild that. We have Ed with us today, so enjoy the ride. We have an amazing guest today. We have Robert Lovekin, M.D. he's a physician, medical school professor at UCLA and USC, and he focuses on the applied science of health, longevity, and consciousness. He's the author of over 200 peer reviewed scientific papers and 14 books that are available in six languages. And after reversing his own primary chronic disease and transforming his life, he's making it his mission to help others do the same. So, Robert, welcome. We love you to pieces. He's one of our colleagues and friends and we're so happy to have you on the show. Thanks for coming on.

Oh, thanks, Wendy and I. I love you guys. I'm a huge fan. I love what you're doing. It's an inspiration and, and it's truly an honor and a pleasure to be on the show today. I'm so excited.

What's mtor? What is it? Why do we care?

Oh, yeah, I love, I love this molecule. It's. It's. I mean, arguably, first of all, MTOR wasn't discovered till the end of the 20th century, so it's relatively unknown. But arguably, it's one of the single most important signaling molecules in all of biology, as evidenced by the fact that it's conserved over billions of years. In other words, it's present in yeast all the way to human beings. So it's fundamental for the survival of cells and organisms. So what does this do? MTOR is a metabolic switch that senses the presence of nutrients. And when nutrients are present, it tells the cell to grow. When nutrients are not present, it tells the cell to hunker down, turn down inflammation, turn on autophagy, or repair, get rid of senescent cells normally an organism would. Will go between states of fast and famine, hunter gatherers, whatever, and MTOR will normally be turned on for periods for growth and then turned off for repair. That's a normal situation. The problem is, and there's an idea not only for chronic diseases, but also for longevity itself, that they're driven by a situation in the 21st century in human beings where MTOR is turned on too much. So it's sort of stuck in the growth mode. What does that mean? Well, it's MTOR sensitive to glucose primarily and insulin, so it's sensing these carbohydrate type drivers, also sensitive to oxygen and things. And while growth is good, when you're, when you're a child and you're growing up, MTOR growth is healthy. There's very strong arguments that turning on MTOR all the time, like we're seeing now in the population, especially as people get older, not only drives the phenotypes of aging, wrinkles, gray hair, hearing loss, menopause, but it also drives the chronic diseases, obesity, hypertension, diabetes, cancer, and Alzheimer's disease. Actually, when you look at longevity itself, MTOR is arguably one of the strongest drivers in longevity. Animal models, in other words, is a drug you can give that specifically targets MTOR and turns it into this favorable position, this repair state. And you can also do it with lifestyle like fasting or dietary choices. Avoiding toxins in your environment turns MTOR into this favorable bar. But, so I would, I would recommend lifestyle as first order. But having a drug that immediately switches MTOR off allows many, many scientific experiments to be done on all these phenotypes of aging and these chronic diseases and even longevity and to document in a controlled fashion, does MTOR really have an effect on all this stuff like people think it does?

So are we trying to turn MTOR on for longevity, or are we trying to turn MTOR off for longevity, which is the goal?

Yeah, great question. We want to turn MTOR on, which is growth and hyperfunction when the organism is maturing, when the long bones are growing, the brain is maturing. But what the theory is that as animals get older, MTOR gets stuck in this on position all the time. This hyperfunction and growth in an older organism doesn't result in long bone growth or brain maturation. It results in hyperstimulation, which drives these chronic diseases that, you know, that we're talking about, and actually, and also the phenotypes of aging and also results in decreased longevity. So there's a drug, one drug that targets mtor Specifically and turns it in this off position. And that was how MTOR was discovered, really, as a result of the drug. Because the drug was discovered first out in Easter island in the 1960s in Rapa Nui. And it was, it was discovered from bacteria there that make it. And they called the drug rapamycin after Rapa Nui. And then later on they figured, wow, this drug is amazing. Its effects on cells. How does it work? And then 40 years later they discovered MTOR. And MTOR of course stands for target of rapamycin, which is. And so rapamycin is a nice drug that we can use for control studies to see what the effect of turning MTOR down is. And when you look at the studies, they're, they're nothing short of mind blowing.

Yeah, just a lot of Davidson Clear's work and a lot of other people. And, and, and to be clear, some people are taking rapamycin on a regular basis these days.

Yeah, it, it's, it's FDA approved. It's actually FDA approved for atherosclerosis, it's FDA approved for cancer. It's FDA approved. Well, it's under study for Alzheimer's disease and it's FDA approved for many other things. But off label uses for longevity, I take it, I take it for that. How many downsides the longevity do the, the first thing MTOR or first thing rapamycin was approved for was renal transplant immune suppression. So that's a daily dose and it's still a frontline drug for that. Um, so you don't want to take it on a daily fashion. And the longevity dose is once a week. And that, that as much as everyone can tell, there are, there are hundred, you know, tens to hundreds of thousands of people taking rapamycin now as this longevity tool just because it's gotten very popular, sort of like metformin was 10 years ago.

And have, do you actually notice, do you have like a noticeable difference or is this more of a long term gain?

Yeah, with, with mtor. The problem is there, there aren't tests to evaluate MTOR function like there is with, you know, hemoglobin glycation with A1C or something. So there's no direct measurement, so you have indirect measurements. Some of the studies, they, they took rapamycin cream, a cream of rapamycin and they mix it with, they have a placebo and they did a blinded study with people for eight months. They did once a day they rubbed it on the back of these people's hands. And then at the end of the study they did punch biopsies of these people, these brave volunteers, but actually they showed once a day application rapamycin dramatically increase the basilar collagen layer and reverse the aging of the skin.

Do we have it in skin stuff? Do we have it in like facial stuff?

Well, the FDA last year approved rapamycin cream as an indication not for wrinkles and aging, but for angio myolipomatosis, kind of a different condition. But it means it's available as a cream now and many people are using it off label for that.

But he's such a buzzcale man.

Yeah, it's. I mean, it's like every single phenotype of aging. You apply it to wrinkles, gray hair, menopause, it, it delays menopause in the, in the mouse model, it slows, it increases the number of pups they have and it delays the onset of their menopause. Is now being studied in humans. They also do it for hearing loss. It sl down hearing loss, age related hearing loss, it slows down periodontal disease, hair loss, gray hair. I mean, they're fascinating things with rapamycin. It's like, how can this one drug affect all these different things? And, and it's fascinating, but obviously you say, well, hey, nobody dies of menopause, right? Nobody dies of gray hair or baldness. Right? People die of. It's a short list. You, me and, and all our listeners are probably going to die of one of about five things statistically. Number one is, you know, attacks and then you go down. Stroke, cancer, Alzheimer's disease. Well, if rapamycin, mtor is so fundamental in chronic disease and longevity, in longevity in particular, it should have an effect on these diseases. Right. So what evidence do we have for it? Well, stents are the treatment today for heart attack, which in other words, if I have a heart attack, a stent which is narrowing in the blood vessels to the heart and blood doesn't get there. A stent is a mechanical way to open the blood vessel. And everyone, depending on their anatomy, they're most likely to get a stent today if they have acute infarct or acute heart attack. And the great thing about stents is they may be life saving in the moment. The, the downside of stents is like, like many of the surgeries or pills for these chronic diseases they treat, they may save your life in the moment, but they don't have an effect on the long term on the disease. So you talk to a friend, just got a stent, and he goes, hey, I'm great. I got a stent. They cured my heart attack. Wow. I dodged that bullet, you know. Wow. Thank you, modern medicine. Well, actually, what he didn't realize is, and many people don't realize, is that the stent will save your life, but it doesn't do anything to your underlying cardiovascular disease. As you know, it continues on the rest of your blood vessels. Clot off, and even the stent will clot off. And that was a problem with stents is they clot off with atherosclerosis eventually. So enter MTOR and rapamycin. They began coating the stents with rapamycin, and it's actually now FDA approved as the number one. It stops atherosclerosis from reoccurring in the stents. And, you know, for that reason, many people are, you know, looking at taking it orally as well for studies that way too. So atherosclerosis is a hyper function. If you think about it, it's not like wearing out of the blood vessel. It's actually hypergrowth, proliferation of cells. So slowing that down by turning MTOR down has a beneficial effect there. The other big cause is cancer. And completely different from atherosclerosis. Right. They're completely different animals, but they're the number one and number two killers for all of us, statistically, that determine literally our longevity, how long we live in these chronic diseases. Well, what does rapamycin do for cancer, if anything? Well, as it turns out, it does a lot. And there's a human model for cancer is people who have heart transplants. The number one, something I didn't know, the number one cause of death in a heart transplant patient is not transplant rejection within the first five years of life, but it's actually a cancer, a malignancy due to the immune suppression from the drugs. And rapamycin is one of the common drugs used, but other drugs are used. So what they did was they, they took these heart transplants patients, and they looked at the ones on rapamycin versus the ones on other immunosuppressants. And the ones on rapamycin had a dramatically lower 30%, lower malignant rate, presumably due to the rapamycin. The evidence is so strong, the FDA now has 8, 8 FDA indications for cancer. For example, metastatic renal cell cancer. Rapamycin is indicated as adjunctive therapy. You know, the number one, kidney cancer and many others. So it also works on cancer. And then, excuse me, there's evidence it works on Alzheimer's disease. And, you know, it's just, it's amazing these, these different Effects, but somehow they're tied into MTOR and growth and inflammation.

Does have any effect on IGF1 or like growth hormone. It seems like it would be tied in closely.

Absolutely. And you know, it may sound like we understand MTOR and we've got it figured out. Well, we don't. You know, this is, it's. This stuff is so complex. You know, David Sinclair is a friend. He talks about sirtuins and you know, different NAD supplements. There's Veratrol, there are other people use Metformin that affects AMP kinase is another signaling molecule, very basic ones similar to mtor. And MTOR is affected by it primarily is affected by it senses. Insulin. Insulin like growth factor like I said, oxygen, all these other things. So, so the things that you mentioned that are, that are anabolic things will tend to tend to turn MTOR on. So the favorable state of MTOR is this essentially a catabolic state where we break things down, we repair things, we repair ourselves and we especially inflammation way down when MTOR is turned down. So that seems to be the favorable state. But the, the short answer is nobody really knows it's it. It's kind of the wild west, but changes are happening really fast. Our understanding is advancing at light speed. So.

Cool. Okay, talk to me about menopause. Do you do any focus. Do you have any focus on menopause? Because sure some people want to delay it, but once you're in menopause is there and women tend to become almost overnight insulin resistance and start to pack on fat. So between the food choices and the rapamycin, have you seen anything for menopausal women?

Because asking for a friend menopause is certainly. Yeah certainly important. And there's growing evidence that, that this metabolically healthy lifestyle which includes avoiding toxins which damage our metabolism will, will have favorable effects on, on menopause. And this is, I'm not an expert on menopause, but just what the, the animal models with, with MTOR and rapamycin on delaying menopause is really interesting. And, and now rapamycin is being used in clinical studies with women to, who are interested in extending their fertility or delaying menopause. And, and all these things and, and we have a fertility crisis, you know, that people say well hey, why do you want to live longer? You know, why do you want to increase the. The your lifespan? Because you know, I grew up in the era when we were all taught there was a population explosion and that we were going to overpopulate the earth. And now, you know, sadly, it appears that's not our problem. Our problem is declining birth rates to even serious levels in Europe and Japan and Korea and China. And so increasing fertility and increasing longevity may to some extent make up for fewer births. But it's a new world out there.

Right. I just want to make sure we're talking longevity means increasing not only lifespan but health span so that we're actually healthy as we age. Not right now, where the last bit of life is in an ICU or a nursing home. We're talking about a healthy, vibrant life.

Exactly. No. Yeah. Nobody wants 10 extra years if it's in a nursing home. Right, yeah. So when we say lifespan, it. Yeah, it's implied a healthy lifespan. And, and that's what, that's what people are finding out. Nir Barzilai is a colleague who's been active with metformin for longevity. And he has a super centenarians project in New York where he studies 100 year olds and 110 year olds and he looks for, you know, how they got to be that age. And sadly there weren't a lot of genes that did it. Which is, which is good news that, well, you know, no matter what our parents are like, we can still change our lifespan with longevity. But the other thing he found to your point was that these older people that live so much longer, it wasn't that they didn't get chronic disease and it wasn't that they didn't. They got it and got it for a long time. It's just they delayed the onset of it. Once they got their, their cancer or their heart disease or whatever, they, you know, they went just like the rest of us. You know, it was so. But the point was they were able to delay the onset of these chronic diseases. And that's what the hope is with, with longevity, with these longevity programs as well.

I've been noticing this in my clinical practice. You know, in med school we were taught average age of menopause is 51 and perimenopause is 45. And I've noticed a huge uptick in an earlier menopause and an earlier perimenopause. So I'm getting women in my practice who are 38 to 42 and they are clearly perimenopausal and their FSH is on the rise and. And then they're hitting menopause at 48 now instead of 50. Like there's just a, it's like a shift, which is just very interesting to see because it's happened in my career, literally in my career, it's there. I've seen the shift. So we're talking 25 years. I've seen the shift and fertility too that I have a couple people who get pregnant with no problem. In fact, one of them is my patient who had breast cancer, recurrent breast cancer, had a mastectomy, had tons of detox work. We spent a year doing detox on her and she got pregnant no problem. And that so many other people have challenges with either sperm count or conception. And it seems to me much more, it seems to be much more than it used to be. Like, I mean I grew up with teen people who had teen pregnancies and it's just, it's a lot less. I don't know, it just seems less now.

Yeah, I mean I, I, I can't wait to pick your brain about microplastics. It's an area that I'm really excited about and I want to get into it. I know you guys are going to come on our podcast. I'd love to, I'd love to talk to you about all this stuff. It is so fascinating and yeah. And you, you guys are the experts on it. So I, I can't be. I'd love to hear your thoughts.

Yeah, I mean it's everywhere.

So how do people find you because you've got so much information? I pointed to the book because it's amazing and read it. People are going to want to know more.

Yeah, my, well My website is robertlufkinmd.com and actually I have a sample chapters you could download if you want to try the book out without buying it or. And it'll be in your library as well. And I'm active on social media and those links are on my website as well also. And I have a podcast that gonna get you guys on soon.

Awesome.

Awesome. We'll put those links in the show notes for the people who are listening so they can, they can click into it. I mean I think this is amazing now, now I'm like I gotta go prescribe rapamycin for you.

You gotta be careful.

That's right.

Work. Don't try this at home. Work with this.

So first is food fundamentals everybody. You gotta get all this other stuff and then maybe we can talk about.

So we can talk about this after. I didn't get up at 3 in the morning. I woke up at 3 in the morning last night, like just awake. I was not happy. Not a happy Wendy. So we'll talk about it when I'm not a 3:00am Human. Okay. So Robert, thank you for being here. This is awesome. I'd encourage everyone to get the book, read the book, go to your site Robert lovekinmd get the chapter, follow you on all the socials, and subscribe to your podcast. What's the name of your podcast?

It's called Health Longevity Secrets.

All right. Well, you've heard it from Robert Levkin, MD. Thank you for joining us on this episode of the Feel Freaking Amazing podcast. And to the listeners, we hope this was inspiring, educational, and empowering for you. So thanks for joining us. Have an amazing time. And Robert, thanks for being here.

Thanks, Ed. Thanks, Wendy. It's been a real pleasure.

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