Dr. David Leonardi, Founder of the Leonardi Institute, joins Jeff Dance to discuss the future of aging, including approaches to prevent and reverse age-related diseases, the difference between aging and vitality, and lifestyle habits to slow the aging process.

Dr. David Leonardi – 00:00:02:

I would recommend that people certainly keep your blood sugar low, get the regular physical exercise, and look into taking some of the myriad of nutritional supplements. You’ll be making a big difference in your long term health.

Jeff Dance – 00:00:19:

Welcome to The Future of a Podcast by Fresh Consulting where we discuss and learn about the future of different industries, markets, and technology verticals. Together, we’ll chat with leaders and experts in the field and discuss how we can shape the future human experience. I’m your host. Jeff, dance. In this episode of The Future of Aging, we’re joined by Dr. David Leonardi, a medical doctor in vitality and longevity medicine and also the founder of the Leonardi Institute to explore the future of aging. We’re excited to have you. Thanks for being with us.

Dr. David Leonardi – 00:01:00:

Well, thanks, Jeff. It’s great to be here. I appreciate you having me.

Jeff Dance – 00:01:03:

Yeah. Really excited about this. I’ve heard you speak a couple of times before. I was always impressed with sort of the wealth and knowledge that you brought forward. Also your own vitality, your energy and your own vitality. It’s like you’re an example of, I think, the things that you share with your audience. So thank you for that. Can you start with telling us more about your background? I know you have a medical background as well, for the audience to kind of get to know you a little bit better.

Dr. David Leonardi – 00:01:28:

Sure. I started my career after medical school in emergency medicine, pretty much the opposite end of the spectrum from where I practice today in preventive or longevity medicine. And I practiced emergency medicine for about nine years. And I began to realize after quite a bit of time in the emergency room kind of late to the party in understanding this, that the majority of the time an emergency physician is fortunate enough to save somebody’s life. In the emergency room. On any given occasion, it’s usually someone dying from a late or end stage of an age related disease that’s most of the time, the emergency of the emergency Physician’s Day is spent with those people. People with obstructive lung disease and coronary heart disease and dementia and osteoporosis and other chronic illnesses. And I began to think, gee, isn’t there more that we can do for these age-related diseases than these last minute heroics? And if you look at our health care system and I have great respect for it, it’s kind of a whack a mole type of process. We wait for a disease to pop up, and then we whack it and we wait for the next disease, and then we do the same. And David Sinclair, who I think you’re going to talk about today, one of the foremost researchers in aging in the world talks about this and talks about how we really should be focused on what we can do to prevent these diseases and slow the aging process. Because aging really can be viewed as a disease in and of itself. And if we look at it that way and approach it from that direction, we can begin to solve the many questions about how and why we age. And then, of course, once scientists, smart scientists, solve those questions, they can easily come up with answers. So in 1986, I switched into family medicine with an emphasis on prevention. But we knew very little about prevention back in those days, and it wasn’t until about 1997 that I went full time into preventive medicine, vitality and longevity medicine. And since I wasn’t very busy with patients at that time, I had an enormous amount of time to keep my nose in the medical literature on the National Library of Medicine and look at article after article and study after study about the chemistry of aging. And it really is all about chemistry. So I acquired a mass of material on my hard drive and began to develop an approach looking at the pathways, the chemical pathways by which we age, and how we can influence those pathways to slow the aging process and prevent the age-related diseases.

Jeff Dance – 00:04:11:

Thank you. One of the things I’ve been impressed with is, after having heard you speak and then having people in the audience, I’ve seen some changes from people that have listened to you and had a better life, had more vitality or more energy or just seemed healthier in general. And so that’s why I was like, oh, I need to hear him again. And that’s why I was interested in bringing you onto the podcast today, but been impressed. So just to summarize, you spent nine years sort of in the traditional medicine field. Then you kind of switch gears into this emerging field, and you’ve been in it kind of ever since. What do you do as you talk to people and work with people? What is like a common thing, a thread to kind of your services? Are you identifying sort of some of the diseases they have and trying to have them reversed in some sense or like they’re just living healthier? What is the core thing that you do as an institute and as a practice? I’ve heard you speak, but from a services perspective, what are you offering your patients?

Dr. David Leonardi – 00:05:05:

Well, our practice is located in Lakewood, Colorado, which is a suburb of Denver, Northwest Denver. And the important thing is that we see patients. We have patients in 38 different states and three continents. The way patients find out about us typically has been from my doing, speaking engagements, and then they contact us, and we can take care of people wherever they live. They don’t have to repeatedly come to Denver. We like to see them once in our office for a thorough physical exam and some other testing on one visit only. But then we continue to manage them, doing follow up blood testing wherever they live in their local hometown. And we get the results electronically, of course. And in this era, technology has got everything covered where we can send the results to them with our notes and get on the telephone and go over the results together just as if we’re sitting across the desk. So we customize the program based on the individual. So we have patients that are extremely healthy and want to stay that way and come to us for that reason. We also have patients that have had some serious health issues and have gotten a wake up call and are hoping that it’s not too late for them. And it certainly is not. I want to emphasize that. So we may have people with pre-existing heart disease, some people with cognitive impairment, pre Alzheimer’s disease, many people with prediabetes or even diabetes itself. And we customize the program to the individual so that we address any diseases that are currently present. But we also get them on a pathway to clean up their cells, to clean up their health and their physiology so that they can reverse the underlying cause of that disease if possible and prevent other diseases and slow the aging process itself.

Jeff Dance – 00:06:56:

Well, I think seeing some of your publications also how often you cite medical research, real medical research this is sort of a new field. I’m sure some people distrust some of the space because it’s new. But every time I hear you, you’re citing real medical studies and the basis in those studies and real science and then seeing people around me that have had results. That’s why, again, I was really interested in going deeper with you on the future of aging. So let’s start with the one on one, though a lot of people aren’t familiar with this. What is your definition of aging?

Dr. David Leonardi – 00:07:31:

Well, there’s the simple layman’s definition where there’s a loss of form and function. And if you just look at a picture of an old person versus someone who’s 25 years old, that’s very obvious. And it’s the changes in form from the cells on up to the systems of the body and the structure of the body that lead to changes in function that cause significant disability. And as we age, of course, our risk of age-related diseases that will ultimately kill us, that risk goes up significantly. So changes in form followed by changes in function and an increased susceptibility to the age-related diseases. But the more scientific aspect of aging involves changes in our cells and our DNA. And so our DNA is called our genome. Pretty much everybody understands that. But there’s another aspect of the nucleus of our cells called the epigenome. And the latest science, primarily from David Sinclair and other researchers in aging itself, is focusing on the epigenome as the primary cause of aging that changes the expression of our genes and how our genes express themselves to affect our chemistry. So the changes in the epigenome cause things to go awry within the cell and the word awry in this case is synonymous with aging. It really promotes debility within the cell. The cell becomes an older cell, if you will, and loses its ability to function efficiently in the organ in which it resides. And if that happens in all of our organs, which it certainly does, then as an organism, we lose our ability to function well and we approach the end of our life.

Jeff Dance – 00:09:27:

As far as how people are dying today and things that are really impacting their vitality. What are some of those top things just for? I know things keep evolving, but is it still heart-related diseases, diabetes, et cetera? Can you tell us just kind of the top list?

Dr. David Leonardi – 00:09:44:

Sure. Well, coronary heart disease and stroke remain our number one killer, and cancer is very, very close behind. And we’ve made great strides in both of these types of diseases. People now with cancer often end up having a chronic disease with repeated chemotherapy and radiation and monitoring. And then we’ve gone a long way in looking at coronary heart disease and stroke and altering how we deposit cholesterol in our arteries and develop blockage in our arteries. And by controlling cholesterol and other risk factors for coronary disease, we’ve been able to delay the onset of coronary disease in much of the population. But then the population gets a little bit older and then still develops the same disease. So we’re still pretty much in that whack-a-mole type of medicine. But what’s been remarkable so those are our two most common killers, coronary disease and cancer. And together they account for about 67% of mortality. And then other diseases like chronic lung disease, of course, trauma, accidents, fill in the gaps.

Jeff Dance – 00:10:58:

Yeah, it’s interesting. If you think about animals and humans, there’s a lot of similar diseases that happen. So it’s like your point of like, this is just aging and we’re going to have these diseases that spur up. But then how do we affect those cells so that we can prevent these issues or delay those issues or allow us to have better vitality while we’re experiencing some issues? I think that’s really interesting.

Dr. David Leonardi – 00:11:27:

Let me add one more thing along that line, is that the classic approach to disease, as I said, was to look at a single disease and look at how we can reverse the disease after it’s already been established. But the most exciting science that’s come to the fore in the last, I would say, 13 years, is the aging process itself literally takes us down the pathway to promote all these diseases. And a much better way to approach life is to look at the aging process and all these chemical pathways by which we age and alter them before we get sick so that we can put that disease off for two or three decades or potentially indefinitely. And that’s where the scientists are focused right now, those that follow and are trying to cure aging. And it’s where I put most of my focus. Although we certainly do take care of people’s present diseases, we want to mainly focus on all that chemistry of aging and how to slow that down or even reverse it.

Jeff Dance – 00:12:31:

Yeah. In addition to the conversation we had with our guests on today’s episode, we asked another expert to provide their insights on the future.

Aubrey de Grey – 00:12:44:

Hello. I’m Dr. Aubrey de Grey, and I’m the President and Chief Science Officer of LEV Foundation. Designing with intent is something that I feel is not understood well enough in science and technology. And the fundamental thing that isn’t understood well enough is the difference between science and technology. By and large, scientists are basic scientists, which means they are interested in finding things out. For the sake of finding things out. They are focused on understanding nature. They are, if you like. Curiosity-driven. That’s a phrase that’s often used. Whereas technologists are interested in manipulating nature for the betterment of humanity. Now, you might think, well, that’s just step two. And the understanding is step one. And in a sense, that’s true. But the problem comes that the mindset, the way of doing things that is required for those two parts turns out to be very, very different, very dissimilar. The way that you use what you already know to decide what experiments to do next. What things to do next. It turns out to be very different. In basic science, when you’re curiosity driven, it’s all about using the most direct evidence. Whereas in technology, in pioneering technology, it’s mostly about leaps of faith, adding two and two and making 17. And that mindset disparity has definitely got in the way of progress in the biology of aging in doing anything about aging over the past few decades. But that problem is going away. The people who were trained to be basic, curiosity driven scientists are getting the message more and more. They’re seeing how their expertise can relate to the translational next step.

Jeff Dance – 00:14:55:

Tell us more about vitality and longevity. Like, you know just the difference between those two. I know that’s kind of a fundamental concept, but help us kind of sink that in a little bit.

Dr. David Leonardi – 00:15:05:

Sure. So when you talk to people about living beyond 100 years old, many of them will just turn up their nose and say, oh, I don’t want to live that long. Because immediately they picture an ancient person with a three foot long beard sitting in a wheelchair in a nursing home drooling. And the truth is, when you slow the aging process and all these pathways and by the way, I’ve only talked about three or so of the ten pathways, when you alter these pathways, you slow the aging process so that you maintain your youngevity or your vitality or not just your lifespan, but your healthy lifespan. So that the plan is at age 100, will be out on the proverbial golf course, if you will, or the tennis court, or you might still be in the saddle in your business, enjoying the productivity in your business, working with your grandkids. Those are the things that we aspire to do. Not be in a wheelchair, in a nursing home. So when we approach aging itself, instead of approaching the individual disease, we literally slow things down so that we maintain we retain our youth instead of getting debilitated prior to death.

Jeff Dance – 00:16:22:

If I get any newsfeed and I start clicking on anything related to health, there’s just a lot of noise right now. How do you decipher what is something that’s true, that you should pay attention to and maybe something that needs more validation?

Dr. David Leonardi – 00:16:36:

Great question. Four words, National Library of Medicine. So if you want to differentiate noise from actual proved science, you go into a website called PubMed, and that’s the National Library of Medicine online, and you can go into a search box and put in any terms you’d like. And if you’re not in medicine, you might have some difficulty interpreting some of the studies. But they all start with abstracts of the studies, which basically is a short summary of the article. And you can actually check on things that people publish in magazines and online and see if the science has been published and actually proven. And the authors will tell you what their findings are, and then they’ll usually comment at the end as to whether this is definitive or whether we need more studies to prove it. And so that’s what I do when people ask me about articles that are in magazines or they see it on television and I don’t know about it already. And I go into the National Library of Medicine and look for very strong evidence as to whether it’s real or not real. And sometimes it is real, and sometimes I find just the opposite, because there are a lot of people that are marketing things that are really not true science.

Jeff Dance – 00:17:58:

I remember talking about biomarkers and biochemical processes with aging. As we think about just understanding aging a little bit more general in general, can you enlighten us?

Dr. David Leonardo – 00:18:10:

Sure. Well, depending on what aging pathway you’re looking at, in many of them, there are biomarkers that we can follow, we can measure and follow. For example, the first cause of aging, I believe, is a process called glycation, which is simply the bonding of sugar to protein. So sugar or glucose is what we burn for energy. It’s a fuel. And proteins are our cellular engineers. They’re the molecules that orchestrate all the chemistry that takes place in our body to support life. And proteins need to be very pristine. They need to be able to have all their receptors exposed. They’re very complex molecules, and they need to be able to interact with other proteins and receptors in the body to do a good job. Sugar or glucose, our fuel, has an affinity to the proteins or an attraction. And when they mix together in the soup, such as the bloodstream or within the cell. The glucose molecules bond to the proteins and excuse the expression. They muck up the proteins, act like glue and cause the proteins to then stick together, which is a very detrimental process called glycation and the formation of what scientists call advanced glycation end products. These complex garbage molecules that gum up our cells, gum up our organs, promote inflammation and oxidative stress, and accelerate us down that aging pathway. And the whole answer to that issue, the way to make a difference in your life is to limit spikes in your blood sugar. In other words, don’t eat the foods that rapidly convert to glucose in the blood. And to make it simple for your listeners, it’s the combination of sweets and starches. It’s not rocket science. Sweets and starches are both made of glucose. They’re very rapidly digested and absorbed into the blood as glucose. The glucose level in the blood spikes dramatically when we eat these, and they immediately lock on to our proteins and start that glycation and advanced glycation end product process and hasten aging. So if you can avoid that piece of pie or that soda pop or that rice, potatoes, bread, other things people aren’t very aware of, those starches that spike blood sugar, you go a long way to slow your aging process and maybe get an extra ten or 20 years of healthy, quality life.

Jeff Dance – 00:20:50:

Appreciate some of the specifics there and also kind of the explanation of the process by which the spiking of the blood sugar creates kind of messes up some of the cellular structure that then ties to the aging process, like, already in motion, essentially. So I appreciate that. You’ve been in this space for what now 25 years. Where do we stand now in our understanding of aging? What hasn’t really changed since you started studying the space and what’s more exciting and what’s sort of like, new knowledge?

Dr. David Leonardi – 00:21:22:

Sure. Well, when I started in this field back in 1997, my focus was mainly on preventing individual diseases. It was preventive medicine, and it was anti-aging medicine, if you will. But it was still a whack-a-mole process because we had ways to prevent each individual disease. But we didn’t really understand much about aging itself. And it wasn’t until around 2013 where the science of caloric restriction began to get published quite effectively, that we realized that there are these pathways, chemical pathways, in the body of aging itself that we can influence. So there are about nine or ten of these aging pathways that have been elucidated by the science of caloric restriction. And just to fill your listeners in, caloric restriction is basically taking in about 33% fewer calories than you would need to maintain your weight. And it’s been shown to extend lifespan pretty much in every species tested by about 20%. So that’s a very significant increase in life. You think of an 80 year old living 16 years longer. That fits with most people’s goals nowadays if they’re old enough to think about that. So caloric restriction is a very difficult and onerous lifestyle, and not very many people, including myself, are willing to undertake that to get an extra 16 years of life. So because of that, scientists have gone in depth to look at the chemistry by which caloric restriction works its magic, and they’ve elucidated these chemical pathways. And there are many ways that we can orchestrate these pathways in our bodies short of caloric restriction that are much easier to manage and permit a much more enjoyable lifestyle and still get the benefit. Glycation is one of them, preventing spikes in blood sugar. And there are many more. And I don’t know how much in depth you want me to get on this. I can go as far as you’d like, but I don’t want to take over the whole interview and take you down a rabbit hole unless you want me to. It’s up to you.

Jeff Dance – 00:23:37:

You’re good. I think we’re not going to have time for all the depth. But certainly having listened to you and kind of thinking about all the different pathways, especially as it relates to these age related diseases, has been really interesting.

Aubrey de Grey – 00:23:56:

The technologies that are emerging which can have a big impact on the postponement of health problems of late life are very numerous. And so I don’t want to try and in any way give a list. What I will say, though, which people maybe sometimes miss, is that most of those technologies are not specific to aging. They are technologies that apply across the whole of biomedical research. So let me give an example. CRISPR. CRISPR is an approach to gene editing, to changing the sequence of DNA in very specific ways that can be used for all manner of purposes. And certainly many of those purposes are relevant to postponing the health problems of late life. In other words, the translational gerontology that I work on. But many of them have nothing to do with that. They have to do with early onset childhood diseases, for example. So that’s okay. Similarly, IPS induced pluripotent stem cells. This is a way of creating versatile stem cells that was only identified 15 or so years ago, 17, 18 years ago. And it’s been transformational across the board, whether it be in aging research or in other medical research, more recently in artificial intelligence. There’s been this amazing new software called AlphaFold, which has more or less solved a problem that’s existed for decades, namely how to predict how to understand the three dimensional shape of a protein starting from its amino acid sequence. That’s basically done. Now, I mean, I’m not saying it’s 100% done, but it’s definitely basically done. These are things that really make a difference. Now, of course, there are other things that are specific to aging, or to be more precise, they are specific to particular problems within aging. But if I were to get into that, I would be here all night.

Jeff Dance – 00:26:12:

I do want to shift a little bit to the future. I’ve been reading a lot recently about breakthroughs. The Time Magazine says reverse aging scientists discover milestone. And Science magazine says research teams reverse signs of aging in mice. And CNN has articles about the same thing, reversing aging. So there’s some notable sources about this that have been coming up and tell us more about the research that a lot of people are talking about right now and how close we are to that as we think about the future.

Dr. David Leonardi – 00:26:46:

Sure. It’s a really exciting topic. And the article or the scientific publication that’s gotten the most press recently is David Sinclair’s study on the information theory of aging. And he’s had this theory for years. He published a fantastic book about six or seven years ago called Lifespan, and the book was, I think it’s tremendous and it’s still a good read today. It’s certainly not antiquated at this point. But he talked about the information theory of aging by then, which was an early theory. And his latest publication in the journal Cell elaborates on that and goes into much greater depth, very much supporting that the theory is correct. And it’s all about that. It’s not defects in our genes that develop over time that cause aging. It’s the epigenome or the winding of our genes around one another and how tightly wound that epigenome stays throughout life that slows the aging process. And so to make that clear, we know that our genes are chromosomes and they’re made of double-stranded DNA. There are two strands of DNA that run parallel and they’re connected chemically, and then they’re twisted into a helical formation, and they’re about 6ft long. Now picture a six foot long string, if you will, that fits inside a cell, inside a cell that’s measured in microns. In order for that DNA to be compacted and fit into that cell, it’s wrapped around these proteins called histones. And the histones are structures that just keep the DNA tightly wrapped. And the reason that’s important is because when the DNA is tightly wrapped around the histones, the healthy genes that are good for us are the ones that are most expressed. And the unfavorable or unhealthy genes are suppressed. We don’t know exactly why, but that’s life. We know this is the case. Now, these histones are not just independent structures. They require assistance in keeping the DNA tightly wrapped. And the assistance comes from other proteins called SIR that also reside along the chain of DNA. And SIR is an acronym for Silent Information Regulators. So the SIR support the histones, which keep the DNA tightly wrapped, which slows and keeps at bay the aging process. Right. We’ve got certs, then histones and the tightly wrapped DNA. Well, the whole process falls apart when the DNA becomes less tightly wrapped or begins to unravel. And the reason that happens is that the SIR don’t have just one job to support the histones. They have a second job, which interestingly, is to repair broken strands of DNA. So all of us undergo about 20 breaks a day in the DNA strand of every chromosome in our body. And so you can see how these cert molecules, they have to leave their post in supporting the histones and run to the site of DNA, break and repair the DNA, and then run back to their histone supporting site and resume their original job. And sometimes they don’t make it back, they lose their way and they therefore no longer support the histones. After that happens for a number of years, the histones begin to lose some of their function and the DNA begins to unravel. As the DNA unravels, unfavorable genes get expressed and healthy genes get suppressed. And that, according to Sinclair and many others, is really how we age. And this is all brand new information, just elucidated in the last, I would say, several years. It’s fascinating. And so the story gets even better, it gets even more ridiculous, if you will, because it’s a concept that we never would have imagined. So about six or seven years ago, actually, in 2006, a very bright grad student in Sinclair’s lab, and I hope I get his name. His name is, last name is Lju, first name is Yong-Ling, I think Young Lung or Yong-Ling Liu, was working on these genes called Yamanaka factors. So this other scientist, years before that found when studying pluripotent stem cells, found that certain genes could take an old cell and when the genes were inserted into the genome and activated, take that old cell and turn it into a young pluripotent stem cell that would be able to differentiate into any type of tissue in the body. So a very immature cell. In other words, it made it young. Well, this grad student in Sinclair’s lab was trying to do this in tissue, in petri dishes and in animals. But there were four of these so called Yamanaka factors, these genes that when he inserted them into tissue or into mice, they were working to make the cells youthful, but they were causing cancer. So he went to Sinclair, very frustrated. He said, look, this science is working, but the cells are getting cancer. I want to try one thing. I think the one gene responsible for cancer, if I eliminate it and use the other three, it might work, but otherwise I’m ready to give up on this pathway of science. So Sinclair, of course, said, go ahead, try it. Get rid of the one you think is responsible for cancer and use the other three. So he did, and lo and behold, the cells became youthful, old cells became pluripotent stem cells, and they did not get cancer. So that’s part of the way that they supported this information theory of aging. And it turns. Out when the epigenome ages and causing the cell to age. That let’s just use for a rough idea. Let’s say a 50 year old human to the equivalent of a 50 year old human. If you insert these Yamanaka genes into the genome and use a trigger to activate them, then you can literally reset the epigenome. You pull all those cert molecules back to their original position where they’re supporting the histones, and the DNA again becomes tightly wound as if it were a one year old. And they’ve done this in mice and actually reversed physiologic age by 25% to 50% just by installing these Yamanaka genes early in life and then using some kind of a medical trigger to activate them. So the trigger they’ve been using is an antibiotic called doxycycline. So this is used commonly. You’ve probably heard of it, had it used it sure, you can use it for lots of different infections, and it can be given intravenously, it can be given orally. And what happens is it reverses aging through the information theory by correcting the defects in the epigenome while you’re using the doxycycline. And then when you get to a certain aspect of reversal, you can stop the doxycycline and go back along your happy go lucky aging pathway for another couple of decades and then use the trigger again, take the doxycycline again for we don’t know how long, several months or a year, and do it again. So theoretically, we’ll be able to take advantage of this science maybe ten years down the line and reset our epigenome repeatedly through life, gaining many, many years of healthy life. Right now it’s pie in the sky. It’s out there. We don’t know how safe it is. We don’t know how effective and reliable it will be. But it’s certainly a very exciting avenue for these brilliant scientists to be exploring.

Jeff Dance – 00:35:19:

The detailed explanation at the cell level, then kind of going back to the macro results. Like, hey, we are reversing aging in organs and our bodies at the cellular level via I think they call it cell reprogramming, right?

Dr. David Leonardi – 00:35:33:

Yes.

Jeff Dance – 00:35:34:

Is really fascinating. Why do you think it’s ten years out? Is that just normal for something at a grand scale like this?

Dr. David Leonardi – 00:35:41:

Well, it seems like it’s going to be here next week. When you read these articles in Time magazine and New York Times, and they’re great articles. I’m not taking anything away from them. But when you get down to the science, they’ve accomplished this in specific tissues. They’ve done it in muscle tissue, kidney tissue. They’ve done it in the eye, actually reversing blindness.

Jeff Dance – 00:36:04:

Yeah, I read that

Dr. David Leonardi – 00:36:05:

From damage to the optic nerve, but nobody’s done it to an entire organism yet. And so in order to do that, nobody’s come close to this, but we would have to be able to insert those genes into every tissue in the body. And that’s a very tough road to hoe because there are certain carriers that can introduce genes into the genome of specific tissues. But each tissue requires a different carrier with different characteristics and so nobody is anywhere near knowing how to insert those genes into a whole organism at this point. Now, if you’ve heard of the science called CRISPR, which is the gene editing science that’s very getting a lot of press these days to cure some terrible genetic diseases, scientists are going in and editing the genome of people with very bad genetic diseases and they’re focusing on one organ at a time. So for example, for glycogen storage disease, you have to edit the genes in the liver and scientists are accomplishing that. And for another disease called amyloidosis, you also edit the genes in the liver. Now, the genes in the liver are very amenable to fat soluble nutrients getting into them. So they’re one of the easier tissues to get into the cell and deliver genes to do gene editing. And so the progress is pretty good for those two diseases right now. But nobody knows how to get new genes into many other tissues. For example, the spleen, the lung, the brain, the gastrointestinal tract, the heart itself, even muscle tissue. So it’s going to be a long time before we’ve started to see some.

Jeff Dance – 00:38:02:

Success with some organs essentially and muscle tissue. But there’s a whole host of organs and components that tie also to age related diseases that we need to be able to affect as we think about a macro effect there. In the meantime, there’s a lot of promise essentially as we think about the future and kind of where this is going in some of the early studies.

Aubrey de Grey – 00:38:27:

What does the future of aging look like in ten or 20 years? Well, honestly, 20 years from now, I think we have a more than 50/50 chance of aging being just done. We just don’t age anymore in the same way that today we don’t get polio or tuberculosis anymore. It’s like that. It’s really going to be like that at some point and I have no idea when that’s going to be in terms of precise predictions. But I feel that as an expert in this field, I have a duty to give a probabilistic prediction and I think that we have definitely a more than 50/50 chance of getting there within 20 years. The particular milestone that I’ve defined that I like to talk about is called longevity escape velocity. In fact, it’s the lev in the name of my foundation. And that is the point at which we have not completely solved all the problems of aging. In fact, it may be a very long time before we do that. But even though we haven’t done that, we have solved enough of those problems to be postponing aging as fast as time is passing. In other words, figuring out progressively how to repair more and more difficult aspects of the damage that the body does to itself throughout life faster than we get to the point where those types of damage accumulate to a level that causes impairment of function.

Jeff Dance – 00:39:55:

If we step back to today then and let’s then bounce back to the future. In a minute though. But as we think about, okay, maybe some of this amazing science will come out. We’ll be taking a shot or something like that, or some pills that are going to reverse some of our aging effects or help us stay younger, reprogram some of our cells. Maybe if we have an organ related disease or a typical disease that we can take something specific to that. But think about today. People are experiencing the effects of aging today age related diseases. What advice would you have for people today while we’re waiting for some of these amazing breakthroughs for the future?

Dr. David Leonardi – 00:40:35:

Well, I’ll answer that in as much time as we have left, but I could talk for hours about that. And this is what I do for a living. We manage people on programs to implement all these cures, if you will, or approaches to the aging pathways. But oxidative stress is one of those pathways. And we limit oxidative stress by having a very clean diet. And that’s kind of a very open term, but by clean, my definition of clean is a very low glycemic diet that minimizes, as I said, Sweets and Starches uses just a modest amount of protein and supplies fat in the form of plant based fats, and hopefully, protein in the form of plant based proteins. These are the aspects of nutrition that minimize glycation and oxidative stress and minimize inflammation. So another pathway by which we age is inflammation. And we can minimize inflammation by avoiding toxins in our life. And those include saturated fats, trans fats, again, keeping up a plant based diet, avoiding exposure to air pollution. I always recommend people use the recirc button in their car to prevent exhaust, surrounding exhaust from getting into the car, because you can’t see, smell, or taste carbon monoxide, but it’s certainly present coming from everybody’s exhaust pipe. And especially diesel particulates are particularly carcinogenic. So I always like people to use the research button in their car. Regular exercise, of course, is critically important, not just for general health, but for brain health and preventing Alzheimer’s disease. And specifically, I like to recommend three or four sessions a week at a minimum of 30 minutes with a heart rate of 70% of your calculated max. And your calculated max is 220 minus your age. And so you want to have a heart rate during your exercise of about 70% of that figure. Then there are nutritional supplements that affect many of these pathways. So one of the pathways that slows aging is called AMPK, and it’s an acronym for Adenosine Monophosphate Kinase, and it’s a chemical pathway in the cell that directs energy consumption and caloric restriction, which I mentioned earlier, activates AMPK. And AMPK activation actually slows the aging process by invigorating the mitochondria, which are the energy factories in the cell and feeding more foodstuffs or products of digestion, if you will, into the mitochondria. So the mitochondria can make more energy for the cell to function at a more youthful level. And one of the ways we can activate ampk short of caloric restriction is with intermittent fasting.

Jeff Dance – 00:43:35:

I was going to ask you about intermittent fasting since it’s so popular right now.

Dr. David Leonardi – 00:43:38:

Yeah. And the intermittent fasting, I think, is very effective. And the easiest way to implement that is just to extend your overnight fast from typically eight to 12 hours, up to 16 hours or so. And you can do that by skipping or significantly delaying when you eat breakfast. So don’t snack at 11:00 at night and don’t eat breakfast till 11:00 in the morning. So if you finish your dinner at seven and then you don’t eat till, say, eleven in the morning, then you fasted for, I think that’s about 16 hours, actually. It is set new math. Yeah. Or so, 14 to 16 hours. And some people will go 18 or 20 and more power to them. And that activates AMPK. It also replenishes another very important chemical in the nucleus of our cells called NAD. And NAD slows the aging process also by because it controls the mitochondria directly. It sends chemical messages, messages out from the nucleus of the cell to invigorate the mitochondria. And then side pathways related to these are things called Autophagy, where when you activate AMPK and you boost your levels of NAD, the cell starts to recycle old beat up garbage proteins that are laying around and converts them into active, healthy compounds that can be used in the cells. So it’s a cleanup process. And Autophagy is when it occurs in our cells, and Mitophagy is when it occurs in our mitochondria, which is another extremely healthy aspect of slowing aging. So you want to activate autophagy and mitophagy, and you can do that by boosting AMPK and NAD. So you can boost NAD by taking a supplement called nicotinamide riboside or nicotinamide mononucleotide. Those are two things that we use in our practice. And you boost AMPK by taking polyphenol compounds that you may have heard of, like resveratrol or quercetin. These are compounds that we’ve known about for decades, and we’ve known that they’re protective against heart disease and cancers. But we didn’t know until recently that they literally slow the aging process by activating AMPK.

Jeff Dance – 00:46:05:

Thank you. So, just to summarize a little bit, since that was a lot to take in, but a lot of good information, having a clean diet is important. And you kind of emphasize plants in that maybe less animal based products, food. You mentioned exercising routinely because that helps a number of things from our systems at the cellular level, you mentioned the air that we breathe. And I know before you mentioned the cleanliness of our water all these things are like intake, essentially, that are affecting the cells. Essentially is sort of what I’m hearing from you.

Dr. David Leonardi – 00:46:45:

Correct. And I’m glad you brought up the water issue. That’s a real easy one for people to implement. I recommend using reverse osmosis in your home and or your office and drinking water that’s been treated with a reverse osmosis machine, which is basically a high tech filter that not only takes out impurities, but takes out the toxic minerals like iron, copper, mercury, and cadmium. So these are inexpensive to buy. They’re easy to manage. And if you look at any bottled water, this is about the cheapest bottled water that you can buy. They’re all treated with reverse osmosis as long as they say purified on the label. If you look at the back, you’ll see they’re treated with reverse osmosis.

Jeff. Dance – 00:47:26:

Any stories? I know you work with a lot of people. You shared a lot of recommendations. I know you go into those in a lot of depth, and this is just like we’re kind of scratching the surface a little bit. But tell us more about what you see with patients that you work with.

Dr. David Leonardi – 00:47:41:

Sure. I’m trying to think of a good example, but there are many people that have come to us who are healthy, but they’re, you know, in that stage of life, maybe after 45 or 50, where they’re beginning to have memory issues, or they’re beginning to run out of energy halfway through the day, or their sex drive is not what it used to be. And they’ve given up sports that they used to play. I have one really interesting patient that came to me at age 53, and he was a dentist, and he was really losing his energy and having difficulty getting through his day at the office. He would go home after work, have dinner, fall asleep on the couch, finally get himself to bed, wake up the next day, and repeat the whole process. And he had a bit of a ponch around the middle and was just kind of waiting to retire. That was his focus in life. When he came to me. We looked at his risk factors. We measure a host of risk factors. We measure bone density and body fat percentage. We measure hormone levels. And we approached all those risk factors as well as put him on a slowing the aging program. And it was remarkable. Within six weeks, his very high risk cholesterol panel did a 180. His energy level skyrocketed. His enjoyment of his dental practice was much greater. He had plenty of energy through the day. He started chasing his wife around the house quite a bit more. He actually had been a softball player and was a very good player, but had completely given it up because of his lack of energy. And he got back on a softball team about two months later, and three years later, they won the national championship in amateur softball. That was about 2020 years ago, and now he’s 67 years old and he’s on an over 65 softball team, and they’ve won the national championship two years in a row. So again, it’s not just about living longer. It’s about living longer and living better. So that’s just one story. There are many like that. That one’s a little bit more dramatic than most other aspects. I had one patient that came to me and couldn’t walk more than one block because he would get aching in the calves of his legs. And that’s because of interruption in the circulation to the lower extremities from the process of atherosclerosis, which is the same process that causes heart attacks. Heart attack is interruption of blood flow to the heart. Well, this was interruption of blood flow to the calf muscle. So we put him on the entire program. We mostly focused on his lipids, or lipoproteins, those aspects of cholesterol, if you will, and we optimized all of those numbers. And within about two months, he was able to walk two blocks, then three blocks, and now he’s about ten years down the line, and he has no issue whatsoever with any restrictions in walking. He can jog on the treadmill, and it’s made an enormous difference in his life.

Jeff Dance – 00:50:54:

Nice. I’ve heard other stories from you, but those weren’t the ones I heard. So it’s great to hear some new ones. What would you say and I’ve listened to you a couple of times, and there’s a lot of recommendations, and I’ve seen people take different recommendations, but what would you say would be, like, some of the top recommendations that you’ve seen really impact people in general? I know that person to person, they vary. You need to do that sort of like specific analysis, as a doctor who’s trained, who also understands the specificity of a person. But what are some of the top things be like, okay, these are three things I would leave with the general populace around aging.

Dr. David Leonardi – 00:51:28:

Well, sure, but just to remind you, I’ve already mentioned exercise, restricting carbohydrates in your diet, and a lot of lifestyle maneuvers. But there are some nutritional supplements that I would really be remiss if I didn’t talk about. And some of those are those polyphenol compounds that I talked about in activating AMPK. I use those quite a bit in my practice. There’s another new set of studies that have come from Baylor College of Medicine in Texas about oxidative stress. And they showed that people my age in their 70s have been depleted in a very important antioxidant, internal antioxidant in the body called glutathione, about 75% depleted relative to a 25 year old. And we’ve known about glutathione being very important in health for many, many years, but we haven’t been able to effectively replenish our glutathione levels as we age. And they actually pulled it off at Baylor. We’ve always known that n-acetyl cysteine is a nutritional supplement that contributes to glutathione production, but we didn’t use another amino acid, very simple, called glycine. And what they showed at Baylor is when you combine glycine with n-acetyl cysteine, glutathione levels skyrocket. So somebody my age in their 70s can actually attain the glutathione level of a 25 year old. And glutathione, again, is a very important antioxidant by taking a combination 100 milligrams per kilogram of glycine along with the same dose of n-acetyl cysteine and replenish glutathione levels. So we’re using this in my practice now. We’re measuring glutathione levels in people before and after and getting great results. Other important nutritional supplements are those used to control homocysteine, for example, which is a not very kind amino acid that accumulates in the blood if we’re not getting enough of certain B vitamins. So I always recommend a specific dose of vitamin B6, B12 in the active form of folic acid for my patients, along with nutrients called an n-acetyl cysteine again, and another one called Trimethylglycine. And we monitor people’s homocysteine levels, put them on these supplements, and we see them decline where they should be down into the lower end of the normal range, which is very protective against Alzheimer’s disease and coronary heart disease. Then there are nutritional supplements to boost NAD levels and slow the aging process. I mentioned these already, nicotinamide riboside and nicotinamide and nicotinamide mononucleotide. And I always recommend, of course, a basic multivitamin so that you don’t develop any vitamin deficiency. And I don’t want to get too much into depth in this and go down a rabbit hole, but there are a number of other nutritional supplements.

Jeff Dance – 00:54:30:

So nutritional supplements are also kind of a key recommendation that you have as you think about aging. It’s not just the intake between the food, the water and the air, and thinking about that. And it’s not just the exercise, it’s also the things that we’re adding, the supplements that we’re adding that can help us be healthier.

Dr. David Leonardi – 00:54:50:

Very much so, Jeff. And the important thing is to know which supplements to take. And that’s what we sort out for our patients. By not just believing everything we read online, of course, we make sure we can justify it through the National Library of Medicine, using the PubMed website, and just going through, if necessary, dozens of articles to really make the case for a particular supplement. And then, as best we’re able, we test for it in our own patients by looking at biomarkers in the blood and through other tests.

Jeff Dance – 00:55:23:

Anything else about vitality and longevity that you’d want to share with the audience you don’t feel like you’ve been able to share? I think we’ve learned a lot today.

Dr. David Leonardi – 00:55:30:

Well, I would just say if people are overwhelmed with all the things we talked about today, it’s easy to think, gee, this is a little bit too technical for me, and get discouraged. Pick one, two or three items that we’ve talked about and implement them into your life and do it consistently. Don’t just do it for a week, but make it a point to remind yourself to keep it up. And of the 30 or so things that I think we can do, I would recommend that people certainly keep your blood sugar low, that’s just focus on that and you might not feel it immediately, but it will make an enormous difference in how rapidly you age. Get the regular physical exercise and look into taking some of the myriad of nutritional supplements that I’ve talked about today. If I mention any specific names, then I do highly recommend them. Those are the three things that you can focus on. And you don’t have to take all the nutritional supplements if you want to pick two or three because you don’t want to be overwhelmed, you’ll still be making a big difference in your long term health.

Jeff Dance – 00:56:36:

Really appreciate your counsel, your depth, and the east of which you explain things. I think it helps to truly kind of understand things at the cellular level, given that’s where we’re learning that everything related to aging and diseases is sort of at that micro level. So really excited about the future as well.

Dr. David Leonardi – 00:56:58:

Well, thanks Jeff. I hope I’ve been clear enough for people to get some value out of this.

Jeff Dance – 00:57:02:

For sure. No, I think it’s been quite valuable and I think knowing also just that, hey, these advances we’re reading about might be ten years out is helpful as well. I think that’s contextually that context and the importance of like, what do we do today if we have an age related disease or we’re in that phase of life, I think is an important concept as well. And so your kind of detailed recommendations and also some of your high level ones I think resonate.

Dr. David Leonardi – 00:57:32:

Awesome. Thank you. It’s great to be here. I appreciate it.

Jeff Dance – 00:57:35:

Great to having you on the show and look forward to learning more from you and really appreciate your wisdom and experience.

Dr. David Leonardi – 00:57:41:

My pleasure. Have a great day.

Jeff Dance – 00:57:45:

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