how is it that we find ourselves surrounded by such complexity. Hello. Hello, you're listening to DNA today, a genetics podcast and radio show. I'm your host here. Dean DNA today informs on what's happening in the genetic world. During my broadcast, I educate you the public on genetic and health topics to event coverage, news stories, book, movie reviews and interviews. Guests include genetic counselors, researchers, doctors, patient advocates and professors. I'm honored to introduce today's guest, Dr. Michael fossil. He's the world's most foremost expert on the clinical use of telomerase for age-related diseases. In 1996, he wrote the first book on the telomeres theory of aging, reversing human aging and has published the sole medical textbook on the topic. Most recently, he published the telomeres revolution which was named one of the five best science books of the year by the Wall Street Journal. Dr fossil earned his PhD and MD from stanford University where he taught neurobiology and research methods.
He has lectured at the National Institutes of Health and the Smithsonian institution and has appeared on Good Morning America CNN BBC and NPR among others. He's currently working to bring telomerase to human trials for Alzheimer's disease with his company till o site and he also has some roots in Connecticut which was interesting to learn. Thanks so much for coming on the show. Thanks girl, nice to be here. Good morning to you. Mhm. So let's start out before we get into kind of all the details of this of just kind of a broad view of what is the telomere theory of aging? Well, it's a misnomer for one thing because in some sense, telomeres are simply one piece of the whole puzzle. And I would love to call it the epigenetic theory of aging or any number of other things. But misnomers aside, what it basically says is that aging is not simply entropy, it has to do with the loss of maintenance. And that loss of maintenance is related to changes in telomere length and it's related to changes in gene expression. But the outcome is very practical, which is human age related diseases.
The other thing to keep in mind is that that as a theory is interesting. But to me, the question isn't what's the theory show? It doesn't have practical applications in medicine. I think we'll get into that because I think it does have been arguing this in General American Medical Association and elsewhere for 20 years. And so for those that maybe don't know what a telomere is, what is your way of describing it for kind of non science people? Well, it's pretty easy to say that it's the end of your chromosomes. But more importantly, it's a piece at the end of the chromosomes that shortens over time and that has implications for gene expression throughout the rest of the cell. And in what ways can telomerase, then slow or maybe even reverse aging. Well, the first thing to remember is that aging is not a universal phenomenon. You know, we tend to think of it that way because everybody we know ages. And dogs and cats and you know, horses and cattle and everything. We think of birds the age. But there are organisms that don't. And more specifically, there are parts of your body that don't example. Most of the people who are listening to this are several decades old, you know, two decades, six decades, whatever decades old, you could argue that every cell in their body is several decades old.
Except that most of the genetic material, or at least most cell material can be your mother, half the genetic material from your father. Um So if you track that back another generation, you have to say that you are several decades plus. However old your mother and your father worked. But the same thing can be carried back all the way back in some sense. Everybody listening to this broadcast is about 4.5 billion years old. And for some reason the germ cell line that resulted in you did not show it related changes. And yet most of your somatic cells do. So to talk about aging. Really, what you have to talk about is not what causes aging, but why does it happen sometimes? And not other times, why does it happen in some cells are not other cells? So the implication is that aging is not universal and that it may be amenable to a therapeutic intervention, which is where we're aiming. And so this therapeutic intervention, maybe a drug or something that increases someone's telomerase. Well that increases the length of telomeres. And I have to say the telomeres per se. Don't matter what we're trying to do is reset the pattern of gene expression to that typical of the younger self.
So it acts like a functional young young, normal cell. Um So telomerase is one way to do that. You could use telomerase, which is an enzyme to re lengthen the telomere. But the important part is to reset the pattern of gene expression. And what are some of the age related diseases that um telomerase or just re lengthening telomeres could potentially prevent or even treat well. Some of them are oddballs and some of them are things that we're all used to. The oddballs are things like progeria. These are the diseases where you have a five year old books, essentially like a seven year old. I used to gather all of them together once a year and we typically have two or three dozen in any given year. But most people are much more aware of actuated diseases. Uh And the most common ones are things like vascular diseases that is strokes. Heart attacks, grateful vascular disease could just a part failure aneurysms. These are aging. Blood vessels with heart attacks being where most people think of this. Um The second major category though really is central nervous system problems.
And there you're looking at alzheimer's which is what as well as all the other dementias including Parkinson's dementia. But there are others for example osteo arthritis in the joints. Osteoporosis in the bones, skin aging which we're all used to wrinkles. For example immune changes changes in the kidneys, renal function. So it's pretty universal. Most people if they don't die of infectious disease or violent death tend to die of an age related disease. And the most common one is the vascular one. Um In most places not always in the last year in the U. K. For example, Alzheimer's suspended leading candidate for the cause of death. And so to really target these age related diseases. There's certain cells really for each age related disease um that you're looking at really targeting. That's true and I sometimes divide this into direct and indirect. For example if I'm looking at your joints, what I'm looking at the cells called contour sights. These are the cells that if you know if you're eating a chicken and you see the drumstick, what you find is this glistening surface and the joint. Those are counter sites and the proteins they create those cells show age related changes and those are the changes that resolved in osteoarthritis.
On the other hand if you're looking, for example at heart disease. If I end up with a heart attack it's not the heart muscle to cause the problem, it's the blood vessel in this case the coronary artery and you look more closely and you find that the cells that line the vessel, the filial cells show age related changes that are the cause in some sense of heart attack, the same is true in the brain. It's not the neurons that are problem. The neurons are sure the innocent bystander, it's the glial cells and the vascular cells that cause dementia in us. So that's an indirect costs again in the heart and the brain. You see indirect aging from cells that are innocent bystanders, you know, cause having problems but they're caused by other cells. Whereas in things like the bones and the joints, it's a direct kind of agent. So sometimes you can have those supporting cells that are kind of showing the wear of age and other times it's the actual cells that are kind of directly involved with the age related disease. That's right. Just to give you another example of this. If I'm looking at heart disease, most people think of heart disease is having something to do with cholesterol accumulation, but it's not the heart muscle that accumulates cholesterol, it's the vessel, It's the heart muscle that pays the price.
You have a heart attack is because you have dying heart muscle, but it's the vessel, that's the cause of the problem. Whether you're looking at it in terms of cholesterol or in terms of cell aging, the cause of the problem is the vessel, not the heart, not the muscle itself, some of the brain. And so by kind of re lengthening um telomeres on these certain types of cells, we can really be potentially preventing these age related diseases from occurring if our cells are all a little bit younger and healthier, That's the magic word, potentially, you know, that's what I first brought up in the American Medical Association 20 years ago last year. But what we know is that this works in certain cases, for example, We have now known for 18 years 19 years now that we could do this in human cells that we take older human cells. You can reset the pattern of gene expression using telomere and you get what looks like functional young human cells. Um now, as of 18 years ago, we first did this in human tissue. When you can find that you can, for example, take old skin and grow young human skin from it.
Or take old coronary artery tissue and grow young coronary artery tissue or old bone tissue and grow young bone tissue in the lab. The question is, can we do this to human patients? That's a difficult task. Um It's only been in the last five years that we've really had the technical tools to be able to take this to human trial based on the animal studies. So that's where we're bound. Next is to see if we can actually prevent and cure age related diseases rather than as it were treating them with bandage and it's a very exciting kind of idea of going into this and saying that, you know, you've you've been part of research that has really shown that this is possible. It almost certainly is possible. Again, we have to see what we can do, But we're pretty confident that we can do a lot better than anything else is going on right now. If I look at for example, Alzheimer's, there have been more than 400 registered trials, registered clinical trials all failed. There are now five or six depending on which way you counted commercially available drugs in the global market that are accepted as treatment for Alzheimer's, but none of them have ever been shown to affect the political course of alzheimer's, they may treat the symptoms, for example, being upset, depressed, anxious, they may treat symptoms, but not the disease.
I think we can do a lot better. The same is true. When you think about things like osteoarthritis, we don't treat an osteo arthritic knee. What we do is remove the joint and put a new one in an artificial joint. But what if we could actually tell the joint to regrow a normal joint? That's a different, different sort of perspective. And with this, not only looking at age related diseases, but also cancer that um by re lengthening telomeres, we could potentially, again, we keep using that word, but we may be able to prevent cancer in that way. How would this work? Well, that's an interesting thing you should raise it because you know there's been a lot of dispute about that over the past two decades. The original and very simplistic thinking was that you sort of had a choice. You can either you either have a natural disease or you could have cancer. And if you if you lengthen telomeres you increase the risk of cancer and you might decrease the age related diseases. But you have one or the other. But in actuality it's far more complicated than that. What you find is that if you have very very short telomeres you have an increased risk of uh mutation, increased risk of Carson a genesis because you're not repairing DNA as well.
On the other hand the cells aren't willing to divide when they have shorter telomeres. So you may have a sense of cancerous cell but you don't have a clinical cancer because it's just one selling. It refuses to divide. Now many cancer cells find a way around that and so they managed to maintain just sufficiently long telomeres, they can divide but not sufficiently long to repair DNA. But what you find is that if you extend D. N. A. Sufficiently, you re institute good DNA repair and so you're probably going to be able to use this to prevent cancer. And in some cases even to treat it. So it's complicated. It's not a matter of long telomeres are short telomeres being good. It's a matter of just how long or how short they are. So it really gets down to if it's too long then it can be bad. But also if it's too short it can be bad. It's finding that middle ground actually. I put it the other way around. I'd say it's very long. Then you have good DNA repair. So you're not worried about the cell division. If it's very short, you have terrible DNA repair. But the cell divides problem. It's when it's just a little bit long enough to divide, but not long enough to repair DNA that you end up with cancer. Okay, that makes sense.
So what are some of the misconceptions that the public and even the scientific community has that you kind of picked up on over the years that you kind of want to clear the air of? Well, the first one is not a scientific misconceptions, popular one. I see this on a number of TV or radio shows and that is the idea that telomeres keep yourself from unraveling or keep the chromosomes from unraveling. Usually people will compare this to a little plastic bag lit on the end of your shoelace? The idea is if you lose the plastic piece in the end and the shoelace unravels. Well, it just doesn't happen. The chromosomes don't unravel. It's basically just that you stop having cell divisions and gene expression changes. So still I I understand the analogy just not doesn't have to be accurate. The much more common one that worries me though is the one I see in scientific circles all the time. And that is the idea that uh it has been aging in cells has to do with telomere length. It's not length, it's changing length. So for example, there are varieties of mice that have telomeres that are literally 10 times longer than mine And that they have lifespans that are literally 40 times as short as mine.
Okay, so people would say, well how can that be? They've got long telomeres but they have short lifespans, it's not the length of the telomeres. The change in gene expression and that's related to the change in length of telomeres. So I suppose you could say it doesn't matter how long your telomeres are. The question is how much have they changed over time? And the real question is how much of the changed gene expression. So this idea that telomere length per se either does or doesn't cause aging, it's just it's again simplistic. It's more complicated than that. It's the change in length and the change in gene expression. Um The other thing I see all the time and this, I see an article come out the literature about once a week, somebody will say, well, you know, I've measured telomere length from a patient and it is or isn't related to something I did or something in their genes, but what they're measuring is only the telomeres in my white cells in the bloodstream. Well, almost nobody, not nobody, but almost nobody dies of old white cells. White blood cells, but the die is as a result of old coronary arteries or changes in the brain glial cells. They usually don't have other things.
I don't mean it's good to have old white blood cells, but they're only measuring one little teeny piece of the body and it's a part that's in rapid turnover. It's not a very reliable part. For example, if I stress you, if you lose your job, you lose your lover, your dog dies, you get a bad viral infection, Everything goes to hell in your life. I'm going to find you have very short telomeres peripherally because they're turning over so fast now. That doesn't mean that you have old white blood cells in the stem cells in your marrow. It just means you've been under a lot of stress recently. If I remove that stress and I take you back in six months and I look again and tell me there's more white blood cells. It may look like your younger. Suddenly. No, you're not younger, they're just not churning as fast peripherally. So that kind of that sort of esoteric technical issue. And yet I see it all the time in the literature. People are measuring peripheral white cells and making grandiose statements that may be true, but they're not supported by the data. And so by looking at that. They're really not looking it's not an accurate picture of kind of the whole picture.
It's looking at such a small part of the body that really doesn't represent the rest of it. You know, it would be like saying, um let's see, you have gray hair and therefore you've got heart disease. No, people with gray hair more likely to heart disease because they're older, but there's no direct relationship there. That's a different system. I can't go measuring how much heart disease you have or haven't on the basis of your gray hair. I should be looking at the current carries the same things to hear. If all I'm doing is measuring your white cells. That's interesting. It's not wrong. But people shouldn't jump to conclusions about what it means in some other system altogether. Example, I know a study that looked at liver cancer and they were looking at purple white cells measuring purple white cells and making statements about the length of telomeres in the liver cancer. No, they may be related. But you haven't proven that in any way. You haven't even commented on it. No, it's just we over over extend the data. I have a question for you in terms of aging and family history in my family, particularly a lot of my relatives have lived late into their 90's.
So I'm wondering if someone like me that has a family history of longevity. If they are more likely to themselves live long compared to people that don't have that family history. Yes. And it may or may not have anything to do with telomeres of course may just be that you have genes that keep down your cholesterol, level your blood pressure and so on and so on or your, you had to 82 illegals. So you're less likely to get alzheimer's than the person standing next year. Um, so it's complicated. However, it is true that, you know, the older your parents and grandparents and so on have lived the longer you're likely to live for any number of reasons I just just alluded to. Perhaps telomeres are related to particularly your mother's, your mother's mother's health. But it's also interesting that the older your father is, the longer the telomeres tend to be at birth. And I think I understand this from an evolutionary perspective, but there are all sorts of these odd little findings. Um, once you set overalls to them, you know that if you really want to live a long life, like your parents wisely that it's not necessarily a lot of people are like um that I hear they say, oh you must have genes for for longevity or something and it's that's not quite accurate to say that I agree with you cara.
Um it's just not that simple. There are genes that cause early, early disease that protect you. But it's not as simple as just you have a gene for long life and a gene for short life or a gene for long term and short term, it's complicated. There's a lot of lot that goes into it just like like height or something. There's a lot of different genes and all eels and mutations that are all kind of contributing to that one feature in someone. I agree, absolutely true contract people say, how can I be sure I'll live a long lifetime. What can I do? And my answer is fasten your seatbelt doesn't have a lot to do with your genes, but it sure can contribute to a long lifespan. What I'm saying is we shouldn't focus so much on what you ate or what your genes are. It's all those things, it's a million things that play a role. How much do we really know about aging and telemetry? In terms of the recent research, we've mentioned kind of a few things of over the past two decades or so. But is there anything that's been ground breaking in the last couple years?
Yeah, there has been, I can think of a lot of things that have contributed to this. The biggest problem we have is that people really don't understand the concept. They still think of aging as as wear and tear and it's not wear and tear. It's wear and tear versus maintenance. But once they get past that concept, which is hard for people to do, whether it's dealing with alzheimer's wrinkles or hard to say once they get past that, and you're dealing with this issue of telomerase and telomeres and gene expression. There are a couple of key papers. One of them probably is a paper that came out of Harvard originally run to penalize group before I moved to texas. And what he did is something I can't do human patients. He read a colony of mice essentially where you could turn to elaborate on and off of the switch. Um that would be like me saying, I can't do anything for your age related disease, but I can help your great, great, great, great great grandchildren, if you let me do something to your OBA. And likewise, the sperm of everybody who you end up having babies with. Well, that's not much of a help, Thank you. Um on the other hand, and remarkable result though, was that you found that you could take older animals and show that they not only regroup brain tissue, which is interesting, but had a number of other features that were important, for example, increased behavioral functions um as well as other measures of disease elsewhere in the body outside the brain.
But another piece that was done was a piece by a collaborator of orange Maria Maria Blasco at sienna in Madrid, it's one of the world's preeminent cancer institutes. And what Maria and her group did was they put a standard telomerase gene for a mouse into a viral vector to hold it sort of like slipping a letter in an envelope addressed to, in this case the cells they wanted and what they found was that they could take place and improve their overall health, improve their lifespan and improve their behavioral functioning. So these mice were much more able to, for example, learn demonstrate memory, get across rotating rods or tightropes than were older mice who at the same age but weren't treated. And the implications for us is that we can use that same sort of approach to treat human related human diseases like dementia. Again, this is something we've been predicting for 20 years, but now we have the tools to do it, which is what's critical. And does any of this research involving CRISPR cas, CRISPR has really been very hot buzzword in kind of even the mainstream um news and everything.
Um or is it a little too early to be using CRISPR? Well, um in a way and again, I'll put this simplistic because it's not entirely true, but in a way, CRISPR has nothing to do with what we're talking about. It's sort of like this, say I've got a symphony orchestra and it has been playing um Mozart And now suddenly it's playing some odd, a tonal thing, a tonal symphony out of the 60s, something odd and I want to fix it well, um what CRISPR does is goes in and trust to retune the violin and return the piano and change the oboe out. Ok, what we're saying is the instrument is not the issue. The instrument still works. What we're saying is a score. So we should take the john gauge score and replace it with a Mozart score, the original score. So we're dealing with different aspects. If the problem with the symphony orchestra is that you have a bad violin, for example, sickle cell anemia or you know, one of the hemophilia says that kind of thing, then CRISPR might be the way to go because you go ahead and fix the violin.
But if the problem is related to aging, age related diseases change in gene expression, then you want to change the score. Not the violence. Has there been any clinical trials yet that are using telomerase or a way of re lengthening telomeres? Well, there's been some interesting ones using a telomerase, activating compound estrogen level and these were sort of, I like to think of them as semi formal studies that were published in peer reviewed journals. In fact, when I used to edit and what they did was they looked at people who have been on these extractable compounds for six months or more and they found a number of indicators that put the biomarkers that were more more typical of younger people. So, for example, if I'm looking at at white cell function, not white cell telomeres or some other measure, but actual functional response to stimuli. You found that people who have been on these instructional compounds had immune systems that function typically like those people who were 10 years younger than they were. That kind of finding is tantalizing.
Now. On the other hand, Our best estimates are that these telomerase activating compounds probably only about five or 6% as effective. That's what we need them to be to be able to do things like reverse Alzheimer's or reverse heart disease. Um they are tantalizing. They're fascinating. There have been about three or four published studies in these now and I am very fascinated by them. But it is not true that we took anybody who is 70 years old and turned them back to somebody was 30 years old. That didn't happen. Still interesting stuff. And for those that kind of have seen commercials that we all have different anti aging. Um things such as skin creams or different things like this. Is there any scientific validity behind this or is it kind of just a marketing ploy? My quick answer is it's the latter. It's a marketing book. So how can they get away with saying, oh we've you know, we've researched this or you know, they say things that sound very science. See well that's a surprise to, you Know, well, you know, I think we're all used to that.
This is not new in human history is certainly not new in the last 100 years and it's certainly not new in the last 20 years. Um I see about about once a month. I see something come across my desk where somebody claims that now have a way of carrying Alzheimer's and it usually comes from the university. The data doesn't bear up. The clinical studies don't work. We even see this with big pharma. For example, It certainly eli lilly was very excited about the initial results a year and a half ago. The Solid is an app study, but they were at best at best statistically postponing it by about eight weeks. And after that, the courses were exactly parallel. The data fell apart, literally gave up in their stolen is about trial. But this is the typical course of almost all of these things when you really pursue them. So people will make claims and sell products. But almost all of these products don't work. Maybe if you do again, there's interesting suggestions that some of these telomerase activators may work. But no, there's very little that can be done. On the other hand, you can understand why people would want to hear these things.
Uh, you know, if I go back for example, in 1950, if I look at some of the ads in the papers for compounds that could be used to prevent polio, which is a huge deal in the us back in 1950. There are all sorts of ads claiming that you could do things that would prevent polio. Very common. In fact, it was the best selling book in 1953 called Diet conquers Polio where people were arguing that if you ate the right diet, your Children wouldn't get polio. Well, that didn't work. But if I were apparent 1953, I'd be buying that book to why? Because there's nothing else. You know, it wasn't until a year later. You begin to have commercially available vaccines that do function. I think that's where we are with regard to age related diseases. If I were somebody with Alzheimer's, I'd be grass beginning and any possible straw and I can't really as a human being blamed people for doing that. And in some sense, I can't blame people for selling it. They're selling hope I suppose you could say, but that doesn't mean it works. It doesn't. And how soon do you expect a product to be on the market? That is kind of scientifically valid. And that can re lengthen telomeres and have the effects that we've been talking about.
Well, we're ready to go to the FDA uh, complete our animal toxicity study that's required by the FDA and go to human trials. We could have human data within two years and then progressing on from there to global global trials. So that's, that's really soon. That's sooner than I thought you would say. Well, it's not as soon as I'd like and we've been, we've been working on this for two years. We're still talking to various investors who have made promises. um, I would like to see it tomorrow. And the tragedy of this is that we probably, we probably could have done this five years ago. We certainly could have done it two years ago. We could do it now. But it's still taking a while to get through. You know, investors, people who have to actually produce the vendors who produce what we need, the FDA committees. There are a lot of things and these are, that's the way life is. I don't have to like it, but I do understand it. And once it is on the market, how long do you think that it could extend human life of preventing these age related diseases and preventing cancer? I think it was Marcus Aurelius who once said something about it doesn't matter how long you live.
It's the quality of your life, whether it's, you know, five years or 500 years and I have to say I'm a little unconcerned about the length of life, but I'm very concerned about diseases. Uh, I used to always say that, you know, I don't actually care what causes aging. I just want to find the single most effective point of intervention in age related diseases. And it is not another statin and uh, you know, uh, vein replacement. It's more complicated than that. Um, so my concern is to treat these diseases and I think we can effectively do that. I think we can actually not just slow for example, alzheimer's but stop it and reverse much of it. What we have to demonstrate that now if the, if the side effect of that is that you live a lot longer as well as healthier. So be it. Um, it's hard to estimate what we could do to the human lifespan. So I'll just stick with, let's see if we can extend the human health span and I think we can pretty confident we can do it. Well, it's very exciting research and I want to thank you for sharing with us today and really giving us a glimpse into um, the potential and where we're headed with us.
Well, thank you very much, europe. Nice to talk to you. So for people that are interested in learning more, you can head over to Michael fossil dot com. You want to learn more about the show or listen to all the episodes. You can go to DNA podcast dot com on twitter at DNA podcasts, instagram at DNA radio and all questions can be sent into info at DNA podcast dot com. I will force them onto dr fossil for those that um, you don't want to ask very expert question. So, thanks for listening guys and join me next week to learn discover new advances in the world of genetics and DNAA