Is Aging a Disease? Inside the First Human Gene Therapy Experiment | Elizabeth Parrish

What were you actually thinking when, when you went to the clinic? Here's the day where you're going to become the first GMO human.

There's a lot going through everyone's mind because we didn't know for sure that I would live. At that point, I believe that I had taken the most gene therapy out of anyone on the planet. Telomerase reverse transcriptase is not shared outside the cell, so we needed to hit as many of the cells as we possibly could. And we couldn't afford to do an extremely large amount of gene therapy, but we did do more than had ever been done before. We felt hopefully that this would be enough.

Hey everybody, we'll get right back to the podcast, but I do have some very, very exciting news I want to share with you, and that is That my new book, Brain Defenders, that we've been talking about on the podcast is now available for purchase. It is going to be published in August of 2026, but it is available now. If you want to learn more about Brain Defenders, go to the website, and that is oddly enough braindefenders.com. This is really empowering information as it relates to charting your own brain's destiny. Now let's get right back to the podcast. We've got quite a program for you today on The Empowering Neurologist. We're going to step boldly into a frontier where biotechnology and longevity actually intersect. Our guest is Elizabeth Parrish. She is the CEO of a company called BioViva. We're going to be talking all about that. And this is a company that is pioneering gene therapy strategies that are aimed at nothing less than redefining, redefining what we call human aging. She is known around the world as the first genetically, or GMO, genetically modified human, genetically modified organism. She made global headlines when she chose to undergo experimental gene therapy herself, an act of what we call scientific conviction that has clearly sparked a lot of debate, curiosity, and certainly extraordinary interest. Her work has been featured in MIT Technology Review, The Guardian, Nature Biotechnology, Vice, The Washington Post, and a variety of international media outlets exploring both the ethics and the promise of genomic medicine, which is certainly what we'll be talking about today. We're going to explore this, as I said earlier, this bold idea that aging itself is a disease, one that may be treatable through targeted genetic interventions. We're going to discuss the genes that she actually received and has been receiving, or began receiving in 2015, how they're made, how they're administered, what are the vectors that are used to deliver these genes, and why, if we redefine aging, this could open the door to really a new era, not in necessarily human lifespan, but at least human healthspan. And we will define these terms. So, this is a very forward-looking, groundbreaking, and A conversation I think you're just not going to want to miss. Elizabeth Parrish, welcome to the podcast.

Thanks for having me. I'm happy to be here.

Uh, we had a great Zoom call the other day. I guess you still call it that. And I, I felt like I had to cut it short because I didn't want to encroach on what we're going to talk about today. But I, as we talked about in the setup, uh, we've got a lot to talk about. But I think our viewers would like to go back to the beginning, as would I. Um, when, you know, all of a sudden you had this epiphany that there needed to be a better way of, of doing things. What happened to you years ago, and when was that?

Yeah, so that was in 2013. So in 2011, I started an advocacy program for the use of stem cells, trying to get the government to consider using, uh, basically putting money back into stem cells, and that the public needed to understand that embryonic stem cells were not fetuses and that the predominant use of stem cells was not embryonic stem cells. That was all very research-based, but autologous stem cells, your own stem cells, had a lot of medicinal benefits that shouldn't be shut down or considered unethical. So I had a couple years in regenerative medicine space and learned enough to know that there was fantastic research in universities and that doctors, medical doctors, were taking this technology offshore and using it in patients to some benefits, but it wasn't really well documented. In 2013, so 2 years later, my son was diagnosed with type 1 diabetes and I was thrown into a world that we really don't know exists in the general public, which is the world of childhood illness. The hospitals, these children's hospitals, are full of kids who need help. And, you know, everything from type 1 diabetes, which is considered a manageable disease, but it's a minute-by-minute manageable disease, all the way to cancers and childhood surgeries, and I guess this really shocked me. It not only disrupted our lives as a family, but it made me realize that this technology that I had been learning about for years now was not translating to the patients who needed it most. So that really is the beginning of the trajectory of my story. I go looking for cures for kids, I end up going to a conference about aging because the professor of genetics of Harvard is going to be there, and I want to know what can be done for kids. And I wake up to the world of the idea that we could treat both sides of aging, the young and the old, vastly with the same gene therapies in many cases, and help them all live a longer and healthier life.

And so, yes. Let me stop you there for a second, because what you just said was really quite interesting. You said, you were looking at treatment of aging. Yeah. And, you know, I think most people might be surprised to hear that, that, you know, we understand treatment of disease states, but here you're talking about actually treating something that we, until quite recently, would consider a normal part of the continuum, that we all expect that this is what is supposed to happen to us. We're gonna age, we're gonna decay, become, you know, less able to carry out our activities of daily living. And so, you're talking, even now, years ago, about this concept of treating aging, I guess, as a disease.

Yeah. Once I went to this conference and I sat through many of the talks, not everyone at the conference, probably very few people at the conference, would agree with me. I immediately thought, this is a disease. Because the pathology of aging is the same in everyone. There are shorter fuses. Some people are more likely to get dementia over cancer, and some people are more likely to have organs fail before other people of their same peer group. But if you cured any one of those diseases, you will just die of another. And so the pathology of aging is succinctly there. And this takes us back to 1960 when we finally encouraged the US government to consider cancer a disease. As you know, it wasn't considered a disease. It was considered a consequence of aging. But before we like inflame and infuriate everyone watching this, there is a difference between chronological aging and biological aging. Biological aging is the disease. That is the biological process of your cells getting older, cellular degeneration over time, and that causing disease. Chronological aging, we want to embrace. We want you to get very old in years. trips around the sun. So, you know, separating those two to make people feel, I guess, less diseased is important.

Well, you know, in my world of neurology, Alzheimer's was considered, and in many regards still is considered, what happens to you. You know, people would say Alzheimer's is old-timers, basically. And statistically, if you know, if you live to be age 85, you've got about a 40% chance in America of being actually diagnosed with that pathological state. The most powerful risk factor for which is your chronological age.

Yeah.

So, you know—

And we can take it deeper into biological age. And that's why people are diagnosed with Alzheimer's, suspected Alzheimer's, at different ages. And so that would incur cancer, kidney disease, COPD, dementia, basically all-cause mortality seems to run at a different biological rate in different people. And that's why you could have 20 people in the room that are all, let's say, 76, and, you know, 20% of them might die in the next year, and 2% of them might go on to be 110. It's a biologically monitored process that has to do with lifestyle, and then it also has to do with genetics.

Right, so you pondered this. This was, you confronted yourself with this reality, You pondered it. So now, what's the next step?

So, the next step of our company in 2013— well, it didn't actually exist then. It took 2 years to develop the company. I had to figure out what was wrong then with this whole system. If there were gene therapies that could potentially reverse aspects of biological aging, and those same gene therapies could treat childhood diseases, and let's just pull out the first 2 that we started the company with. Telomerase reverse transcriptase is a hallmark of getting old. So, um, the, the consequence of not having it, let's say. So our telomeres, the caps at the ends of our chromosomes, shorten with every cellular division. In 24 species, including humans, lifespans are tied to that shortening. Now, you're— it's not a perfectly measured biological aging clock because your telomeres can stay short at the end of life for many decades, but the diseases of aging that you are diagnosed with come when they're at about 5,000 base pairs. Your cells then go senescent, so they no longer divide, so the telomeres don't get shorter, but they are a measure of disease. That gene therapy itself can also treat progeria, which is accelerated aging in children. So they have a Lamna A gene defect. It creates more progerin in the cell and it degrades the telomeres at the ends of the chromosomes. These kids die of the same diseases that we die of in our 80s in their teens and early 20s. So we know telomeres are a big problem with biological aging. Another gene therapy that looked like it was super beneficial already in children with muscular dystrophy, but on the other hand could be recatered to an aging population and people who have something that's called sarcopenia, or muscle loss with age. Well, we wanted to take that, expedite the use of it, and create a combinatorial— the first combinatorial therapy to treat aging. This took a 2-year process of a lot of research, trying to find funding for companies who were already looking to do this and them just giving up the technology for us to do it ourselves. So in 2015, I launched a company And the premise of the company is that we are going to treat humans. We are not going to treat mice anymore. There is enough evidence in these gene therapies that it actually benefits their lifespan and healthspan. And I become the first test subject.

Okay, so here we are. What year is it? 2015. And you have this company, and you are personally convinced that there's enough data, animal data, that you're going to go ahead and have these genes inserted into your cells, basically, using a viral vector. We'll talk about that in just a little bit. And the 2 that you chose, again, were follistatin and TERT?

Yep.

Okay, so again, the, the first is designed to inhibit myostatin and therefore take the brakes off of muscle growth, and the second is to amplify telomerase enzyme to maintain or perhaps even lengthen your telomeres.

Correct.

Okay, so what happened?

So what happened is, well, we started the company in January of 2015. I needed to raise money to do this. A lot of investors walked away. They hung up the phone. If they were in person, they just stopped talking and kind of slowly moved out of the conversation. I finally found someone who believed in me And thought that this was absolutely the right thing to do. And they funded the project. We had the therapy made, and I traveled out of the country to take it.

So we— let me just take a breath here for a moment because, you know, we've got a lot to talk about. But you saw this, these issues in animal research showing positivity, and you form a company You end up manufacturing these genes. You go offshore, and you have the very first person on the planet injected to have these genes injected into your body. What were you thinking at that at that point? I'm not saying what were you thinking. I'm saying what were you actually thinking when when you went to the clinic and the day is here's the day where you're going to become the first GMO human.

Well, I think that, like, probably how people depict that in their mind is like, you know, we're putting on our capes and we're thinking we're gonna save the world. But actually, you know, there's a lot going through everyone's mind because telomerase reverse transcriptase had not been used in a human, not especially as a full-body experiment. So we didn't know, for sure that I would live. We didn't know for sure. I'm not— at that point, I believe that I had taken the most gene therapy out of anyone on the planet because we had studied all of the clinical trials, and that was a very large dose. Now, since then, they have exceeded that and shown that if you exceed certain amounts, it's toxic. So luckily, we didn't do that. But we had already done a lot of estimations. There are genes That, like follistatin, that you could put here and here on your arms, and they actually share the protein throughout your blood system. So the protein goes into your blood, it blocks myostatin, and has a myriad of benefits of lowering inflammatory markers and other things. Telomerase reverse transcriptase is not shared outside the cell. So we needed to hit as many of the cells as we possibly could, and we couldn't afford to do an extremely large amount of gene therapy, but we did do more, I did do more than had ever been done before. And we felt hopefully that this would be enough.

So before you underwent the treatment, you must have had a battery of before labs done. What—

We did, yeah.

And I don't, we don't want, I'm sure there were countless, but you were looking, I would suspect, at things like metabolic markers, inflammatory markers, measurements of IGF-1 growth, insulin-like growth factor. So you had a really— and a telomere length, I would guess, as well. Obviously, you're looking at the delta there. So you have this whole baseline of laboratory studies. You go to the lab in some country. I don't know if you're able to tell us what country. You could probably tell us the country. But anyway, so you go there and the needle's in your— wherever the needle went. Is it intravenous?

Well, the therapies, I've taken them intravenous since, but at the time, because telomerase reverse transcriptase, the one that lengthens the caps at the ends of the chromosomes, had never been used in a human, we did over, I believe, 150 injections, the doctor said, all over my body in cancer-prone areas, sun-exposed areas, because I really needed to make make sure that it didn't kill anyone down the road. And so it was, I felt like I had come in contact with a porcupine. And I remember at the end of it, each one of the injections was pretty cathartic considering that I felt like I was in a battle against childhood disease and that we might be able to create therapies that could save millions of people. It sort of took that pain away of seeing all of those sick kids. And really, you know, like when we work on aging, as you know, we look at all-cause mortality every single day. And it's, it's pretty grim. And so on one hand, there was that, but I remember the last few injections, me saying, yeah, that, that's enough. And I think that those ones were, were put in my hamstrings. That was for fulastatin, and I'm not sure that we do hamstrings anymore. That one is a more painful shot, but I had already taken so many shots over my body. I'd had my stomach hollowed out and under the fat in one area to put a pocket of the gene therapy as well. So I was pretty tired by the end of that. Wow. But it was, you know, before we went into it, of course, I texted my kids that I love them. And, you know, it was kind of like, you know, you have that moment where it's like, you know, everything that we've been building up for has been paperwork and wonderment and waiting for orders to come through and making sure that we didn't get stopped. There were only like 3 people who knew I was going to do it, not my family or anyone. And, you know, you get there and then it's like, oh, and now, you know. We don't know what will happen, but it was, um, it was important, and we knew it was important, and nothing was going to stop us.

Um, the criticism, uh, in, um, many, uh, much of the media has been, uh, that it was, you know, more than cavalier, that it was, um, really, uh, you know, in almost inappropriate, as, as you know. I'm not telling you something you don't know. And yet, um, I think you portray yourself as being a vanguard, you know, as being a pioneer. And did it— did that help you with the fear? You must have had some fear at the time of the administration.

Yeah. I mean, we didn't— we didn't know what would happen. We had studied these therapies for 2 years, and there was a definitive line between these— the gene telomerase reverse transcriptase causing anything hazardous And the longevity studies.

So we— In the animal research.

In the animal research. So we felt very confident that at least this was probably the most promising drug for human life and health extension on the planet. And for a single gene, it still is. So, I mean, the media— so, I mean, you do something and you risk death, and when you survive, you risk your reputation. And I've had no problem with the kerfuffle that it caused because we—

Kerfuffle, okay.

Kerfuffle.

I think it caused a little— I don't know how diminutive kerfuffle is, but I would venture to say that that's an understatement. But go ahead, sorry.

We disrupted a lot of—

There you go.

A lot of areas. We disrupted a lot of parallels in biotech. One thing, biotech used to raise a lot of money and used to be able to infinitely do mouse studies. And those money raises almost were like profit to those companies. And we came out and said, if the drugs don't work, you shouldn't raise a cent on them. These drugs, science was built to improve human lives. And if it can't do that, then it has no future here. And we also started to unveil different people's research that they had done for decades to see if it was real or not. And, you know, so I mean, from how drugs get funded to how we move development forward, we're not going to talk about things anymore. 36 million people will die this year of biological aging. And I am a vanguard. I am a person who is here to make sure that patients get access. And since that therapy that I took, we recreated the first licensing partners in the world that would open these gene therapies to medical tourism. We opened investment opportunities for companies who would translate more quickly to humans. And I went back to school and got my MBA in regulation and started helping countries actually open up safe and ethical regulatory pathways Pathways to get patients treated. So I am tireless in this. I still stand— I don't feel shamed by what we did. And I think the only sad thing about it was at the time I really didn't know how to manage the media. But the media's reaction was strong, and that shows that we did something very important.

Good. Yeah, either way, and that's good. Has any research come out more recently that makes you question, for example, the safety of telomerase?

No. The research just is more definitively showing the benefits of this gene therapy. And now that we have 4 or 5 licensing partners, we're about to have the 6th one in the US, which is fantastic. We are seeing just more and more data that is pointing to that these people are healthier, they have better immune function. As we saw in COVID-19, immune senescence, meaning short telomeres in your immune system, was a lethal cause of death in that condition. And so when they tested people's telomeres and their T lymphocytes after death, they all had exhausted immune systems. So lengthening those telomeres makes it so your immune cells, your T lymphocytes, can actually divide to attack an invader. And when you don't have that, that is consequential. Idiopathic pulmonary fibrosis is starting to get signs that lengthening telomeres might be the definitive pathway for these patients. Neurocognitive, we released a paper years ago that the first dementia study with gene therapy in the entire world where we used Klotho and telomerase reverse transcriptase to see improved cognition in those patients. And this tiny amount of TERT actually made their immune system telomeres longer.

Hmm.

So that was— and, you know, these patients were followed for years. It's a requirement of the company that we get at least 5 years' data. So we We're seeing healthier, more radiant patients after using this type of technology.

Hey, everybody. We're going to get right back to this podcast in just a moment, but I wanted to tell you something really exciting about 40-hertz light exposure. We have actually done a podcast on this. We know that when you're exposed to 40-hertz stimulation, this is linked to what we call gamma— increasing gamma activity in the brain. In other words, balance in the brain. which is really a fundamental for brain health and brain functionality. In fact, in early clinical research using what's called 40-hertz stimulation, researchers have reported signals that are consistent with a slower decline in cognitive function in some participants. So the company that we are talking about, who is in fact sponsoring our podcast today, is OptoCeutics. Their Evy— I'll call it Evy Lite— is designed to bring 40 Hz light and sound into a simple at-home routine that you can use while you're reading or watching television. I use it actually while I'm working on the computer. Optocytics makes it easier to try, so you can get 90 days of risk-free trial with support from their care advocate, somebody who's going to work with you. And, if it's not creating value, then you're able to return it to Optocytics for a full refund. And, How can you lose? They're going to pay the shipping both ways. Quick note, Evi is a wellness device, and it's not intended to diagnose, treat, or cure, or prevent any disease. And this episode is, as I mentioned, sponsored by the Optosutics company. So if you'd like to try it, go to optosutics.com and use the code PERLMUTTER26 and get $200 off your order. I think you're going to find this device to be really quite amazing. Let's get right back to our podcast. You brought up clotho, so let's talk about alpha clotho. And you—that is now part—that's available for people to receive as well. Many have called that really the prototypic longevity gene. I guess taking away some of the spotlight from TERT. But that said, I mean, you know, this obviously getting a lot of press. People are talking about ways of naturally upregulating. But here you are in your company, correct me if I'm wrong, but you've created the alpha-clotho gene as to be used, administered at these clinics that you describe. And so what are you seeing in terms of people who are recipients of alpha-clotho?

Yeah, we just got the patent approved on that. So this is exciting. So in 2020, we decided to work with a nonprofit to see if we could get patients who had dementia with suspected Alzheimer's access to a dual gene therapy, Klotho and TERT, and we were able to do it. Everything was paid for for these patients. They came down to Mexico, I believe, in this case, in an investigator-initiated clinical study, and they were administered these 2 gene therapies. Now, before they went, I stuck with my promise, and months before they went, I went and took the gene therapy myself. We've improved on it a lot since the first version of it. We have a better way of administering it, but it's directed intranasal delivery with needles because AAV doesn't transfect well through the mucosa.

So you're injecting it up through the cribriform, or where do you inject that?

Yeah, well, the protocol is for the company, but I can ask if you can have access to see that. But we have—

Okay, yeah, we can do that offline. But so now we're talking about the— a third, for our viewers, a third gene therapy called alpha-klotho. In addition, in these patients with cognitive impairment were diagnosed with Alzheimer's, that they're getting telomere elongation or stabilization, And this anti-aging, direct anti-aging gene that works via phosphate and vitamin D metabolism in the cell. And so, what did you find?

Well, their cognitive scores went up.

That shouldn't happen. I mean, right?

And we started switching the tests out. We started with the full steam test. I believe we worked to the MoCA, and then we started to work with just some, like, you know, hand-drawn up different things that they shouldn't be able to do. Their cognitive scores went up and it lasted almost 2 years before we saw the decline again. One of the patients was able to go from assisted living back home. Some patients knew their loved ones again. Patients started painting. One patient had no benefit, unfortunately. We don't know why. But again, it's dementia with suspected Alzheimer's, so we're not sure what happened there, so it's not 100% treatment, and it wasn't a cure. But it improved these people's lives significantly, and the families were all super happy to be part of that, and it helped us look at the data and look at how we can improve those therapies. And so now we're working with Dr. Sheldon Jordan, who's super famous doctor working in neurosciences, and we're working on a new protocol to get more of the gene therapy to the specific areas of the brain, the hypothalamus in one case and the hippocampus in the other case, in order to drench the lining of the cells that are responsible for memory.

Well, um, I would say that, uh, just for our viewers, let's be clear. We don't have an FDA-approved meaningful treatment for Alzheimer's disease. It does not exist. The drugs that are currently used are drugs that target beta amyloid. Do they effectively help reduce beta amyloid in the brain? Yes, they do. But that doesn't necessarily translate into any change in terms of cognitive decline. The rate of cognitive decline is a little bit slowed, but Elizabeth, what you just described is an improvement in cognitive function. So You know, it's breathtaking. Is this the answer? I don't know. Is it a piece of the puzzle? I would say absolutely. We couldn't— we shouldn't turn our back.

It's not a definitive cure. It's definitely a piece of the puzzle. When upon autopsy— this paper came out like a year after we did this study, which was very validating— upon autopsy, patients who had all of the signs of Alzheimer's, the beta amyloid plaques and the shrinkage of the brain who didn't have cognitive issues, did not show the cognitive symptoms of the disease, were all natural alpha-klotho upregulators. So just working with—

Interesting. You need to say that again. So these people naturally had higher levels of this longevity gene called klotho,

uh,

and, and these people did not have cognitive decline?

That's right.

Though they had the So-called hallmarks of Alzheimer's disease that, had they had cognitive decline, would have ascertained the diagnosis.

Yeah.

Fascinating.

We would love to work with a company that's also doing the beta amyloid plaque removal and use the therapies with it. But right now, you know, we'll be working on exacting the gene therapy, getting more of the gene therapy to the centers of the brain that need it with a better delivery combination with this ultrasound-guided therapy and exosome-encapsulated AAV. And I believe that then we'll see major score changes, and then we will start working in combination with other companies who target other problems of Alzheimer's. I mean, the beta amyloid plaques are a side effect, and it could be a side effect from a lot of different things that are going on.

Well, it takes me to a— I need to move the conversation a little bit laterally because, you know, we now understand that the accumulation of beta amyloid is really an immune issue. It's a shift in the brain's immune cells, the microglial cells, from being in a phenotype or a description in which they reduce the formation of beta amyloid and actually are able to phagocytize it or basically digest it away. And the activity of these microglial cells is really, uh, strongly influenced by their metabolism. And when I say metabolism, I'm talking about their mitochondrial function. That leads me to another type of gene therapy, and we talked about it before, called PGC-1 alpha.

Yeah.

And so PGC-1 alpha is a gene therapy that targets mitochondrial biogenesis, the growth of new mitochondria, and fosters better energy metabolism utilization on the part of cells throughout the body, including the brain's immune cells, the microglial cells. As such, one would expect that amplifying PGC-1 alpha expression would allow these microglial cells to do good things as it relates to getting rid of beta amyloid. And therefore gene therapy, as it, you know, would then be something we should consider. targeting these microglial cells, their mitochondria with PGC-1 alpha. And I think you're doing that work, aren't you?

Yeah. So PGC-1 alpha was the next place we had gone to. PGC-1 alpha had been looked at and discovered around basically creating better function in Parkinson's patients. But we wanted to reestablish it as a potential therapy, as a 3rd arm to this dementia study. So when we looked at telomerase reverse transcriptase, we looked at the research behind it. It actually seems to have a reparative effect on mitochondria in the same cell by reducing oxidative stress. Now, there is a complete feedback loop between mitochondria and longer telomeres, and so it had been shown in research this feedback loop. So we were excited about that. Also, lengthening the telomeres created less tau tangles in neurons, and so we're excited about that. Alpha-clofo was associated with less beta amyloid plaques. So there is a cross between. But when we did the therapy, the complication of the protocol that's harder to describe is we were targeting different cells with different gene therapies. So the neurons and the microglia were targeted with different AAV gene therapy deliveries, and the microglia were targeted with the alpha-clotho. Today, we have a completely different association with a set of cells that we will be targeting, even though we will still target those cells. And then PGC-1 alpha, so yes, it's associated with mitochondrial biogenesis, Turning white fat to brown fat with this excessive amount of little mitochondria that darken the stain. But we'll be talking about— we can't talk about yet— we've got a new way to do this that is going to be a delivery in which creates a certain cell type to donate mitochondria to all the cells around it. And we're going to use gene therapy to do that, but we can't talk about it clearly.

Hey everyone, we're going to get right back to this podcast, but first I wanted to share some information about olive oil. You know that I love olive oil, so here's a good tip. The most delicious olive oil that you can get is olive oil that comes fresh from the farm. This is when the olive oil is at its peak flavor and all the nutritional, uh, good things that we talk about, the polyphenols, etc., are really at their peak. When you buy your olive oil at the supermarket, you are getting an inferior product because they have been sitting on the shelf for months and they basically grow stale. And that's why I've been getting my olive oil direct from small award-winning family farms really around the world, thanks to a fellow named TJ Robinson. I've done Instagram Live with him in the past. He's known as the Olive Oil Hunter. He's sort of the Indiana Jones of olive oil. He is able to source farm fresh oils that are vibrant, they're healthful, they're grassy, they're incredibly delicious, and you can use them on whatever you want— on salads, fish, vegetables, meat, and even like I do on scrambled eggs. So if you want to taste the difference that freshness makes, TJ is going to send you a full-size bottle, which normally will cost you $39. He's going to send it to you for free if you pay them just a dollar. That will cover shipping. And that's how he then is able to introduce all of you to this Fresh Pressed Olive Oil Club, a club that we are members of. So there's no commitment. Just send him a dollar. He'll send you a full bottle of olive oil. You just want to go to getfresh389.com. That's getfresh389.com, and he'll make it happen for you. Let's get right back to our podcast. Yeah, so, so we do know that that's actually already happening within our brains, that cells that have neurons that have defective mitochondria receive through microtubules donor cell— donor mitochondria from healthier cells, and that one of the LK variants that is associated with increased risk of Parkinson's, for example, is a failure to form those microtubules. So this is something that's already going on. So I think I heard you say you're developing a cellular donor scheme whereby a cell can be introduced that can then donate healthy mitochondria to cells that need it.

Yeah. Yeah. And these will not only be healthy mitochondria, but they'll be, you know, from Your own cell line in one case. We're also doing a donor cell line where we'll have 7 lines of cells for donor mitochondria. But yeah, one of them would be donated from your own cells. Healthy mitochondria, even if you don't have them today, we can make your cells make them.

So just a comment for viewers, we've talked before about this PGC-1 alpha, this So it's a protein that then is helpful as it relates to your mitochondria. And how we upregulate PGC-1 alpha, of course, are things like exercise, getting enough sleep, reducing stress, you know, all the normal players, caloric restriction, et cetera. But I, you know, what we're talking about, Liz, is, you know, a way of keeping that switch on all the time in a much more effective and dramatic way. So you mentioned the delivery system, and I think traditionally what you and your company have done is called an adenovirus sort of delivery system. What does that mean? I mean, some people hear adenovirus and you're injecting a virus, that sounds kind of scary. Tell us what it's all about.

Well, there's 2. So there's adenovirus, which is a large virus, and it is the one that kind of shut down gene therapy in 1990, due to an ill effect. There's something smaller that eats on adenovirus. It's about this big in comparison, and it's called adeno-associated virus. And the thing is, is that it has— most people have seen it. It has very low immunogenicity in humans, and it can deliver genes evading the immune system with immune suppressants, of course. and deliver small gene loads. And so it became the darling of research, I believe, in the late 1990s, and then started clinical trials in the early 2000s. And so this is the therapy that we use because outside of companies in the United States who have used too large of doses, it's actually a very safe gene therapy to use. And the worst-case scenario is something like a fever and then very little uptake of the gene. And that's probably what happened in one of the dementia patients.

There are other delivery mechanisms, one, of course, using lentivirus. And tell us about the big difference in terms of integration between the adeno-type delivery system versus the lentivirus type.

The reason that people love adeno-associated virus is it vastly, 90-some percent of the cases, creates what's called an episome. So it means it doesn't integrate into the human chromosome. And when it does, it's been found in places that have no oncogenic effect, meaning it doesn't cause cancer. And that's really fantastic. Lentivirus is a larger virus. But it is a retrovirus, and our genome unfortunately has a lot of docking sites for retroviruses, and they're known to cause cancer. So lentivirus immediately wasn't something that we wanted to work with. We wanted just to work with something safe that didn't disrupt the natural human chromosome. And so that's what takes us into the area of adeno-associated virus.

Other clinics seem to be offering plasmid-type delivery systems. Can you walk us through what that means?

That means a very, very short-acting amount of just a genetic string, and so whether or not, you know, I don't really know the efficacy of those. They may be viable for short-term expression, but they're not what the science is

So, um, in terms of continuing to do things in your body, how do you, uh, how do you measure that the gene therapy that you underwent initially or— and continue to get, how do you measure that it's still doing something in you?

Yeah. So, um, with telomerase reverse transcriptase, we year after year have looked at my telomere length. And we look at that every year and we just see this slow lengthening. And then every time I take the therapy again, we see a bump in telomere length, which is, which is really fun because that kind of shows us biologically how that's working. With other gene therapies like alvaclothone, follistatin, we actually look at protein in the blood. So we have ELISA kits run in third-party analysis to see if the protein levels actually changed. And so that's how we can see that it has. And then we continue to monitor patients over years to make sure that it's up. And then we also use that for redosing. So we're the first company in the world that's done AAV redosing successfully. We can show with our protocol that we We can get increased protein expression. And so in those patients, we like to watch it too. And we were seeing that already with the telomeres, but we didn't start redosing AAV until 5 years after my first gene therapy, because we had to do a lot of work to figure out how we could do that without having an immune response or rejection.

And I saw images, cross-sectional images, I believe they were of your thigh.

Yeah.

And that you, you know, that some pretty significant gain in muscle mass. And, you know, it's great that we gain muscle mass, but I think in the context of what's the opposite of that, sarcopenia, we know that sarcopenia, or the progressive loss of muscle mass, is really powerfully associated with a lot of degenerative conditions, not the least of which is cognitive decline. And, you know, we now embrace muscle tissue as being, you know, virtually an endocrine organ creating great chemicals for the body and specifically for the brain. So the more muscle mass we have, the more repository we have, the internal pharmacy, if you will. So, you know, that's, I think, another argument in favor of the follistatin/myostatin approach to gene therapy.

You know, David, what I love about your podcast, just being here right now, is usually I have to go all the way back to basics. And doing research on you, I knew that I didn't.

Oh,

good. You know, and, you know, this isn't like the first time, the first rodeo that you've done, and you know what's actually happening for patients. And it's just, it's such a delight. It's very rare that I just get to answer short, you know, answer questions. But you're absolutely correct. And follistatin, it's turned out since I did that in 2015. It's actually involved in a myriad of different biological processes, including brain plasticity, and that was not known. Reducing TGF-beta inflammatory markers, that was not known. It's believed to be protective against both breast and prostate cancer. That, when I did it, was not known. So this single gene is very consequential for all people. And, you know, people would watch and they'd say, well, I can go work out and I can eat right. And so I can upregulate some of these genes, but we have to remember, why are we here? Those are the laws of diminishing returns. You're not going to get past 120 doing that, that the body starts making less of these proteins. We call it loss of gene function over time, and we can see that even in healthy subjects. We can see that over time. So that's why, in case anyone's wondering why you would bother doing a gene therapy over— you should work out, you should eat well, but if you can increase a natural human gene function to help you support your activities, to support your diet and exercise. Why not? You could see it either way. You could see either one of them being a supportive role in your life.

Hey everybody, we're gonna get right back to the podcast, but I have a very important message for you. You know, why do we exercise? Why do we pay attention to how much sleep we get and the quality of the sleep we get? Why are we looking at our diets? Because ultimately we are sending information to our genome. We are affecting our genes. affecting how our genes express themselves. I like to know about my genome. That's why I'm a real fan of the 3x4 Genetics Test. Why? So you can learn about your genetic predisposition. You know, in my world, as it relates to the brain, there are some genes that in fact are associated with increased risk for neurodegeneration. A lot of people know their APOE status, for example. But I want to be super clear that this not a genetic determinant. Maybe it's a genetic predisposition, but what you're seeing here happening, these are our lifestyle choices that actually change our gene expression. You should know about your genome. You should get the 3x4 Genetics test. We'll talk about how to do that in just a moment, but there is a health program that they offer you as well. When you get your genome sequenced with 3x4 Genetics, it's not just getting the information, but they're going to tell you what to do with that information. So, I think that's really very important. So, head on over to 3x4genetics.com/DrPerlmutter. That's D-R Perlmutter. They have a special offer for you and all of you podcast watchers. Let's get right back to the program. Well, getting back to the muscle mass, one of the myokines that's produced with greater muscle mass, you know, producing all muscle, but more muscle, more production of these myokines, is irisin. And we now understand why irisin is such a tonic, because, you know, getting back to what we were talking about before, it aids in the conversion of white fat to brown fat. And that fat is brown, as you pointed out, because it has more mitochondria. So that's why exercise is mitochondrial therapy, not just through activation of PGC-1 alpha, But through eiresin as a myokine converting white fat, we call it the bronzing of fat, and, you know, basically increasing mitochondria and therefore energy utilization, keeping blood sugar balanced.

That's good for the brain as well. So, you know, there's a lot to think about. Since you were first, there have been obviously lots of others. What is your sense in terms of what people are experiencing?

Well, when we work with companies, we license technology, and then there has to be a level of safety, and they have to follow the protocols and everything else, but we don't want to know who the patients are. We're not interested in that. We don't want any direct correlation. We just want to see the data. Occasionally, these patients walk up to me, and it's amazing to hear directly. So we see numbers. You know, they tell us their life experience and how it's changed their life. We had one— so alvaclotho has a myriad of uses, and one of them is for chronic kidney disease and cardiovascular disease. And we had a patient who was on the donor list, on the list to get a donation of a kidney, and had to and immediately needed one. And he took the gene therapy directly, image-guided, gene therapy to the kidney, he came off the list for 2 years. And to see him in front of me and say— and he wasn't sad about it, you know, because like to me that's a huge disappointment. He came up and he said, I'm the person who took the gene therapy for chronic kidney disease. I needed an immediate donation. I was 2 years off of the donor list. I'm back on it, but I'm okay with that. And I wasn't okay with it. I was like, damn. But he was okay with it. It got him 2 years. And it's really inspirational, you know, to see people who have Parkinson's disease or Alzheimer's and being sent videos from them being, you know, confined to kind of pretend jogging down a hallway with no walker. And yet it's not a cure. And so it's like, it's killing me. Literally, that we have to move faster. So, you know, I get to see the beauty of the short-term response, and a year or 2 to someone means a lot, but we have to do better than that. That's just not success.

You know, it makes me think about many, many years ago when I was a much younger man. I was— it was determined, it was learned that a certain part of the brain was deficient in glutathione, an antioxidant detoxicant that does various things, uh, in, um, and it was seen to be related to Parkinson's. So I thought, simple enough, if Parkinson's brains have low glutathione, let's give them glutathione and see what happens, you know, because people were— It's relatively safe. So I began doing this to my Parkinson's patients and filming them And posted on something early on called YouTube. Crazy. It was very earliest experiences on YouTube.

You pioneer.

Pardon me?

You pioneer.

Yeah, I know. And, um, so, uh, you know, there's the video is this very sweet gentleman, um, who is really, you know, aggressively compromised by his Parkinson's, gets his glutathione shot, and then we video him, I think, 20, 30 minutes later Now he's walking down the hallway and he's smiling and he's happy. And his wife called me a week later, said he's been up on the roof replacing shingles. And I'm thinking, that's not exactly what I wanted to hear. But anyway, but the interesting two things happened after that. First, people were really, you know, kind of amazed. But some of the comments on YouTube were that he was obviously a paid actor. Okay, well, you know what it's like. And the second, you know, response was that, you know, this is kind of an off-label type of thing. And, you know, why are you doing it? And there was no downside. But so I know what it's like. You know, I really been there. And I every once in a while I go back and look at that video and think about, you know, that's what we need to do. We need to push. And, you know, It's nowhere near what you did.

No, it is. Because the thing is, you saw something, you saw a mechanism of action that could help. And so those patients need access to that. And what happens is you push, and first there's nothing, there's no echo, and then the echo comes back and tries to knock you off your feet to stop you from doing it. And it doesn't make sense because these are the type of things that we have to band together and figure out how do we cure these people. Because, you know, today 110,000 people will die of biological aging, and not to mention the children and a myriad of accidents that might have been foreseen or stalled if we could think faster or, you know, had a better, smoother-running community out there. And we are the vanguard of making sure that this, this This happens and that we don't get knocked down by someone saying, you shouldn't do that. You shouldn't do that for somebody who's dying, to somebody who's suffering. It's their choice. And when you have a patient with, as you know, with dementia or anything, you're not just saying, hey, you're not cognitively functioning well, how about a gene therapy or how about some glutathione? You actually have to get their family to sign off on it and their medical doctor. So it's not just— you're not trying to go around, you're not trying to hurt anyone, you're trying to save lives.

Yeah. I remember when, when that, that glutathione video finally was posted and all the, you know, people were raising their eyebrows. The comment was, well, you know, you really need to do a double-blind placebo-controlled trial and publish it in a peer-reviewed journal. And I thought, it's working. Why do I need to do that? Okay, we'll do it. We did do it. And we did it at University of South Florida and the movement disorder clinic. And it proved, incredibly effective. And yet, uh, you know, people— well, we're aware we are at this time, here we are 2025, uh, that we're still just treating symptoms. We're just treating rigidity and tremor. We're not treating the underlying disease process. And I think if we focus on what you're doing more than anything is treating the fire, not just the smoke. You're treating the upstream issue here. You know, the, the the primordial issue, not, you know, not the manifestations. We in America, in the Western cultures, just focus on treating the manifestations of disease. In, you know, in, in your son's case, it's treating the high blood sugar. It's not treating the autoimmune loss of the beta cells of the pancreas. Mm-hmm. It's treating the manifestation. That's what insulin does. That's what metformin does in the type 2 diabetic. But we're missing the boat on the underlying problem. Let me explore with you where we go in the future.

So why we look at these gene therapies is because they're treating biological aging at the cellular level. We're not, you know, targeting, you know, genes that just, you know, have some sort of effect of, you know, masking a symptom. We're actually trying to make the cells younger. And so, you know, that's where we're going to continue to go. So, you know, there's 12 agreed-upon hallmarks of aging. It's going to grow because it's a wish list, right? And it's the things that are driving the processes of cellular degeneration or the inability for the body to restore itself and regenerate. And so when we look at that with gene therapy, we have so many gene candidates and there's so many of those hallmarks that we can target so far. So we're looking for more genes. We're looking to put together more combinatorial gene therapies. Of course, we have to raise money to do all of this, but we're very, very careful. We don't let any investor in because we are so agile. We can do first in many areas that larger companies can't do. So, you know, where we're headed is the combinatorial gene therapy, hopefully sooner than later, that keeps your cells in homeostasis, keeps them from degenerating faster than they're regenerating. And so what that looks like for humans is, you know, a homeostasis of the body in which you're not degenerating, you're not getting weaker or frailer. over time, but you're staying in a state of ultimate health. And then around that will be human enhancement. And so every one of these gene therapies, you know, already we go under fire because they are half enhancement and they're half preventative medicine. And that's what therapies of the future are going to look like. Mm-hmm. So if your muscles are stronger, it's an enhancement, but it's also a preventative medicine against type 2 diabetes and metabolic disorders. You already talked about if your mitochondria function better, it's the same thing. It's an enhancement. You're going to think faster, move faster, do things better, but it's going to protect you against, again, cellular metabolic issues. Lengthening your telomeres, that is by definition creating immortality, even if it's just because Cells that couldn't divide 10 extra divisions can. That's called creating cellular immortality in a dish. We're creating that in the human body. And that is to break lifespan, this bottleneck limit, because if you're healthy, you shouldn't die of anything. You shouldn't have this wall that you hit. I mean, mostly we talk about healthspan and not lifespan, but they go hand in hand. And so, you know, we want people to ultimately live as long as they like and enjoy their life. And there'll be some comment under here that will say, well, I can't stand this world. And it's like, that's clinical depression, and we're very sorry for you, and we're working on those areas too. I have my sights on a lot of companies that are working towards depression, and as those You know, and things that we want to stop, all things that make life not worth living. And that would also be mental state. And, and I do think that the world will be a better place when people are living longer and they have to treat each other better.

One last thing, and that is how we— how you and I got connected. So,

okay,

several weeks ago, I'm on the elliptical machine and learning about gene therapy, as one would expect a person would be doing on the elliptical machine, of course.

Why not?

And there was Peter Diamandis, um, introducing you, uh, and you, you gave a talk. And I did what everyone would do, of course. You know, you get— you see a talk, it's very interesting, you reach out to the person. I'm going to connect to that person and chat. So for our viewers, Liz and I spoke— what was it, like a week or two ago? And, um, I've enjoyed every minute. I, I am, uh, I'm so honoring of, of what you're doing. And, uh, you're way on one side of the bell curve, which is a great place to be. And I've always said that, um, the mission isn't to be thinking outside of the box. The mission is to make the box bigger, more inclusive. Yeah. And I think that at the end of the day, that's, that's got to be your goal, that this becomes You know, I know it's going to be a long time till this is standard of care, but at least let us begin to embrace the potential here and check the boxes of safety and make these things, you know, put them in a place that we can make them verifiable and do all the work that needs to be done so that they become acceptable. But I am very, very thrilled with what you're doing and grateful that you spent time with us today on the program. Thank you.

Absolutely. I mean, it's just so wonderful to be here. And as the years go by, you're going to see one more and one more regulatory system open up to treat biological aging and use gene therapy. And in 2024, we worked really hard and the Bahamas passed a law to do such things. And they will be running clinical trials, as you would expect, to get these drugs into the US FDA regulatory system. And then I also have a best choice medicine plan for the US, for the Human Health and Services Department. And we're trying to get that passed as well. And I believe there's even going to be a march in Washington, DC about it in 2026.

Wow, there's a lot happening. So how can people stay on top of this evolving story? Where can they go to keep up to date?

They should follow you. I imagine you'll continue to have conversations with me as we have new information. And then, well, you know, BioViva, the company, has its own social media. I have my own social media. Most of the things on there, though, are value-added. We— I specifically read papers almost every day, and I Make it so you are getting what's happening in science today. It's not necessarily about the company in 99.9% of the, the cases. Science moves too slow for that. So I want to tell you everything out there. I want you to get excited about that. We've got a new project called Trial Atlas that's going to be coming out. That's an AI system that will help people find access to clinical trials.

Wow.

Learn about the genes behind their diseases. And of course, you can always reach out to any of the clinical partners if you're interested in what that looks like, but we always suggest that you go through a proper US clinical trial if it's available first and foremost before you go outside into medical tourism. And that's about it. Wow. So just look for what we're doing and we'll keep you updated. You can get on newsletters or whatever, but following you is one way There

you go. And I will tell our viewers, if you look at the bottom of your screen right now, you'll see some great websites to go to follow and learn more about this. Liz, thank you so much for your time today. This was really fascinating, that's for sure, and encouraging.

Thank you for having me.

Okay, my pleasure.

Thank you for everything you do.

I appreciate it. Well, that was an extraordinary conversation, wasn't it, with, I would say, a trailblazer reshaping what we believe is possible in medicine. Targeting aging at the genetic level isn't science fiction anymore. And as Elizabeth Parrish has placed herself at the center of that whole evolving story, there's certainly a lot more that we will be learning in the years to come. And I think really in the short term, whether or not we agree with every approach, the questions that she is bringing to our attention and the courage that she's shown, and I call it courage, these things signal a future where aging may truly be seen as a modifiable disease state. So, thank you for joining me here on The Empowered Neurologist. I'm Dr. David Perlmutter. We'll be back next time. Stay curious, stay empowered, and remember that the future of your health really is being written right now in terms of the choices that you are making. So, again, thanks for joining us. Thank you. We'll be back soon. Bye-bye. Bye-bye.