Many of us strive towards living long lives; but just as health risks grow as we age, we might say it’s quite a challenge. Dr. Eric Leire, a thought leader in the area of longevity and life extension, is aiding this goal. He is the CEO of Genflow Biosciences, a longevity gene therapy biotech that is driven by one mission: to deliver therapeutics that potentially halt or slow the aging process in humans and dogs. In this episode, he joins Doctor Awesome to tell us more about their origin story and the science of what they are doing. Dr. Leire also talks about health span versus life span, the role of AI in this revolution in aging, and how they are tackling the longevity issue with gene therapy. Beyond the technology, Dr. Leire then gives some great lifestyle tips on what we can do to maximize the likelihood of getting the long life we want. So follow along to this great episode and hear about the future of aging.

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The Future Of Aging – A Conversation With Dr. Eric Leire

We are talking with Eric Leire who is a thought leader in the area of longevity and life extension. Eric, tell us a little bit about yourself, what you are doing right now, and how you are pushing this field forward.  

I have been involved in longevity through gene therapy. Gene therapy is a bad word it seems for people. It’s a million-dollar therapy. Gene therapy is progressing at a tremendous pace. I thought it was possible to apply all the gene delivery technology to longevity. I’m in favor of a stochastic explanation of aging, accumulation of random damage in the DNA, and epigenomic changes. This is regulated by genes that have been identified. We started to understand the biology of aging, and we identified those genes. I saw that the tools we have developed for gene therapy could be applied and be a very good solution for solving the issue of longevity. That’s where I come from.

I’d love to hear about your company. Tell me about your company.

I created a company a few years ago. It’s mostly based on the work of Vera Gorbunova. She’s a professor of biology at Rochester University in New York. In 2019, she published a very interesting paper on cells. The idea is she looked at rodents. In rodents and the rodent family, you have a huge discrepancy in life expectancy.

You have some rodents like mice. They live 2 to 3 years. On the other hand, you have beavers or naked mole rats. They live 30 years. That will be a tenfold difference between primates. You see such a difference. We don’t have such a difference in humans, so we all die more or less in the same period. That was an interesting thing. In that paper, she was able to correlate the longevity with the quality of the Sirtuin 6. She exchanged the Sirtuin 6 gene to gain time and she was able to extend or decrease the lifespan.

What’s very interesting in this paper is that the difference between the Sirtuin 6 of a naked mole rat and a mouse was very small. Sirtuin 6 is a small gene and the CDNA or the portion that’s coding is relatively short. It’s 1,000 base per square root or a protein of 350 amino acids. There are two amino acid changes in the CTML portion at the end of the protein.

It was a relatively five times amino acids change between naked mole-rat and rat and a ten times difference in lifespan. That was something stunning. That paper was like, “Whoa. Could we have a better Sirtuin 6 gene in a human or find a better one?” We have a good Sirtuin 6 because we live relatively long, but we are not the mammals that live the longest. There are a lot of mammals that are smarter than us and live longer than us, but we are in the good one. We live longer than horses.

I would argue it’s smarter. We are the smartest mammal. I have a very optimistic and proud view of humanity.

The idea was can we find people with better Sirtuin 6? With Albert Einstein College of Medicine, Columbia University New York, and Rochester University, we looked at centenarians. We sequence the Sirtuin 6 of 450 centenarians in 550 controlled homogenous populations. We found a mutation only in centenarians. Vera Gorbunova was able to understand the mechanism of why this centenarian version was better than the wild type. It was mostly on the ribosylation. Sirtuin 6 is a very well-known gene and the Sirtuin in general. The link between Sirtuin and aging has been done by people like David Sinclair in Boston.

He has been very famous for selling a company to GSK, but activator Sirtuin is difficult. He was a big promoter of Sirtuin 6. Sirtuin 6 is interesting because compared to the other Sirtuins, Sirtuin 1 and Sirtuin 2, it’s a small molecule or gene. It goes from one protein. This Sirtuin 6 has only two mutations at the end of the gene on the ketamine section of the 350 amino acid protein coated by the Sirtuin 6 gene.

We know that it’s not through the deacetylation portion, but more the ribosylation. We know that this is linked to a better ability to repair DNA breaks, especially the double-strand breaks. Compared to the wild type higher ribosylation of part one, it has a much better ability to repair DNA damage, especially the double-strand breaks. It has also a better ability to inhibit line one, so the transposing. That’s the oldest joint DNA we have.

That was quite interesting. There was a possibility to patent it. We patent it and we created a company. We have the exclusive license on this and we developed it. We want to be a longevity company. Maybe I should stop already on longevity because you are futuristic. I’m afraid that if you want me to say, “We will live 150 or 200,” that’s not my main objective. I’m sorry.

I’m also an MD. I’m a pure product of evidence-based modern medicine. Modern medicine did a fantastic job of increasing our lifespan. Many years ago, life expectancy was 40 years, now it’s 80 years. We gain a second life. It’s amazing. The issue is most of us waste a second life fighting one of those age-related diseases like cancer, cardiovascular disease, neuro disease, and diabetes mostly. The gap between the health span or how long we stay healthy and the lifespan or how long we live is increasing. We progress but the health span is not that much.

I give you 30 more years, but you will spend these years in dialysis and going to chemotherapy 3, 4, or 5 times. This reality, you couple that to two other factors. One is the fact that for the first time in human history, we have a different demographic distribution. I have been told in school that demographic is simple. It’s a pyramid. There are a lot of young guys and very few old guys. Unfortunately, it’s changing for the first time, and for the people who tune in to this, you may be aware that it’s not only in developed countries. It’s a Japanese problem. It’s an Italian problem. It’s worldwide. For the first time in human history, there are more people aged over 65 than people under 65.

There’s no more pyramid. That’s a big problem because our healthcare system and our pension system are all based on a large base of young people taking care of a few. That’s not sustainable. It’s even not sustainable because as our medicine is getting more and more sophisticated, the cost of the medicine increased. You have a larger population with bigger needs for healthcare and more expensive healthcare. This is not sustainable. You can do whatever you want. There’s no way to escape that. The only way is to work on longevity. Getting our healthcare to become a real healthcare. Not a sick care.

As our medicine is getting more and more sophisticated, the cost of the medicine increases.

I agree with you for all of those reasons that you talked about. I want to take a step back and say that I’m so excited to talk to you for a number of reasons. Number one, you are also an MD like myself. I feel like that simpatico is there. Number two, the way that you broke down that very complex concept was well done so that everybody could understand it. That’s going to be so important in the whole longevity movement. The ability to tell a normal person why it’s important for them to care about this is something that needs to be at the forefront of the whole movement. I have spoken with Aubrey De Grey. Are you familiar with Aubrey De Grey?

I saw him at ARDD in Copenhagen. It’s a big week. Aubrey was on the scientific advisory board before. Now he is moving with the lab. He quit the SENS. He’s a very nice guy. He’s fantastic.

I spoke with him. He was promoting the Yamanaka factors. We do need to talk about that. I promise you we will get to that, but I wanted to first say how excited I am to talk to you. That prefaces the situation because it’s important. The idea of Yamanaka factors is huge. It’s very popular, but my point is that we have to have some sort of broad-based gene therapy available for a whole host of diseases.

The idea that you are tackling the longevity issue with gene therapy is another thing that I want to talk with you about because my background is in craniofacial genetics. That is something that we are eventually going to get to. I wanted to preface this by saying we are going to talk about longevity, but I also want to talk with you about genetic disorders, which are very close to my heart. I don’t want to forget about it because I know this is going to be an involved discussion. Let’s talk about Yamanaka factors. Explain to the people what Yamanaka factors are and the promise that they hold for longevity.

Yamanaka is famous because he gave his name for the four factors, OSKM. There were two. They were a Japanese and an English guy, but Yamanaka is mostly the guy who gave the name to the factors. When I went to med school, it was very clear that we were getting embryogenesis. We start with the germinal cells and the somatic cells. In a way, we are immortal because our germinal cells are immortal, and for the human, our somatic cells are dying.

The original version of stem cells came from a tumor that was from a human being who has long since died. Theoretically, on the cellular level, we could be immortal. I agree with you.

When I was in school, what Yamanaka was doing and what we were doing every day in the lab was nonsense. I would not go to the next year in med school if I had said, “We can go from IPCs to very differentiated cells.” The flow was going down and there was no way to come back. It’s impossible. That was it. That was the truth.

Yamanaka came and he was trying to solve the issue of whether we can get stem cells through another source than the embryonic. Because of ethical issues, people are not comfortable, and it will be so much more comfortable. It was more than that. It was a revolution. The flow doesn’t go one way. We can go back and that was fantastic. You put the four Yamanaka factors. You take a fibroblast and you can get an iPSC. Your potent stem cells are the stem cells that can do anything. It could be a fibroblast. You can differentiate in a hepatocyte. It’s a tool that every lab is using now every day.

We use Yamanaka on the object. I’m working with a guy in France. He did even better than Yamanaka. They had two other factors and he was able to not only take fibroblast but a senescent fibroblast from a centenarian. He was able to add two factors and two additional growth factors to get to iPSC. It’s extremely flexible and it changed everything because it changes our mindset. Aging is plastic. We learn aging goes one way, but no. Aging could go the other way. There was a lot of excitement to say, “We should inject that.”

When you say excitement, I’m so glad that science is exciting again. I feel like for a long time it has not been. Let me give you an example. This guy Carlos, the gentleman in the longevity space came and spoke in Cambridge, Massachusetts, at the hotel across from where I lived. This was a huge auditorium. It was so packed that the fire department had to come and say, “You have to clear out because there are too many people in this auditorium.” People were standing up. It was like a rock concert. The excitement for this particular technology is huge. I want everybody to understand that. My wife is not interested in science but I want her to know that this stuff is interesting.

Everybody should be. In science and medicine, there are fields that are not particularly interesting. When I was a student, infectious disease was nice. I first went to surgery and I did a kidney transplant. When I said to my boss, “Infectious disease is nice.” He said, “Are you joking.” We have antibiotics. It could be something from the past. It will never happen.

Infectious disease is a dance between a pathogen and a host.

We then had HIV AIDS and it was a revolution. It was so exciting. It changed everything. It changed not only the science but the way we communicate and interact with patients. It changed everything. Oncology, chemotherapy, and then you have this immuno-oncology came. For ten years, it was a dream. People are saying, “Immuno-oncology and the immune system to fight cancer will never work,” then you have CAR T cells. You have checkpoint inhibitors.

Right now, the excitement is in longevity. I went to ARDD. It’s a five-day conference. In five days, you start at 7:00 AM and finish at 7:00 PM. You have one presentation after the others. They are all fascinating. There are so many smart people. We start to unveil aging. What can be more important than that?

The idea of changing aging from an inevitability to a disease that we can treat, my mind exploded when I first read that.

It’s not only people. I see the medical professionals. Let me take an example. I am in perfect health. I go for my checkup and I see my cardiologist. He takes my blood pressure. He was like, “You have 18 on 10. I receive your cholesterol. Your LDL is okay. We will do nothing. Those are not diseases. You didn’t know. You don’t have symptoms.”

What should you recommend? I should run out of the office of this cardiologist and see another one who will treat my blood pressure, will treat my cholesterol, and give me a statin. Everybody will laugh and say, “Poor Eric. He went to see the crazy cardiologist.” Now I go to my general practitioner or my family office. I said, “I’m getting older and I forget names. The stairs seemed higher now. I’m out of breath. I used to run through the stairs to get to my lab on certain floors. Now I have to walk down the stairs.” “Eric, it’s aging. You have to accept it,” and I should not.

It’s a risk factor like high blood pressure. Like high LDL. It’s the same risk factor. We had a perfect illustration of COVID. Immune system. The same virus and all the research is focused on the virus. It is good. It was a low-hanging fruit that was the vaccine. Perfect, but we should remember that infectious disease is a dance between a pathogen and a host. One thing about COVID is some people or kids who get COVID say, “I’m positive. I didn’t notice.”

The same virus killed the guy with the immunocompromised system and it was all about age. Age is a risk factor. We start to understand the biology of aging. We start to understand that not only do we know the drivers, but we can act on those drivers. In animal models, we are able to extend the lifespan or health span of animals.

Like the mouse. The Methuselah Mouse is what people are talking about.

There’s so much to understand. It’s fascinating. Not only do we understand, but also there’s one thing that’s fascinating for me. It’s the AI or how AI is coming. I’m like you, I’m an optimist. I’m fascinated and we start to understand the biology of aging. It’s even more complex than cancer. It’s multifactorial. Our brain doesn’t like multifactorial. It’s difficult for us. We like one cause and one consequence, and simple relationships.

That’s difficult for us, but multifactorial is difficult. AI is just deep learning. Now at the ARDD for example, the conference was from people like mathematicians. They get this huge amount of data. They look at the microbiome. They look at the transcriptome. They look at the DNA and RNA. They look at the proteome. It’s massive data. We cannot make sense of it, but with AI and the people in Silicon and Geo, that’s amazing. That’s fascinating. I’m so lucky to be part of this revolution.

I’m hesitant to bring AI into this as a topic because I worry that it takes away from the gravity of longevity itself. I feel like AI right now is a buzzword that everybody is using in the same way that people were using crypto a few years ago. I know it’s not the same. You and I were both under the same impression that I know it’s not the same. I know that there are going to be profound benefits of it, but I want people to understand right now, AI aside, we are living in a period of exponential growth in the longevity space and honestly, the genetics space too.

I feel like genetics is something that we knew about for a long time and it hasn’t produced the results that we wanted it to. Specifically in the longevity space, there are people like Aubrey De Grey and David Sinclair. You can talk to anybody on the street and they know exactly who you are talking about.

That’s not the case for other types of fields. It’s not the case with something that has a profound impact on our world like AI. Who’s the number one AI researcher? I can’t shout it off the top of my head, but people know David Sinclair. They know Aubrey De Grey. They know that longevity is out there, but it hasn’t given us the same treatment that is available for other things.

Just like what you are saying. I go to my primary care physician on a regular basis. Before I chose that physician, I had to go through maybe 5 or 6 of them. Every single person, I said, “I want to live to 150 or until 120 and in good health. What can I do right now that will get me there?” The majority of people were like, “That’s not what I do here. That’s not interesting to me.” I found somebody who’s like, “The longevity space is interesting. I don’t know what to recommend to you, but let’s work on your risk factors first. Let’s stop the eating of bad food. Let’s get your VO2 max to the most that it can be.”

We can outlive.

The next person that I was going to bring up is Dr. Attia, who has come out with this book Outlive that you are referencing. He has the idea like, “These are some things that we can do to maximize the likelihood that we are going to get to the longevity technology.”

Peter Attia recommends more or less the lifestyle change. On the lifestyle change, you can have a marginal benefit. I don’t think that will bring you to 150, but it will start to help bridge this difference between the health span and the lifespan. For the people who didn’t look at Outlive, it’s a fantastic book. There are a few things I’m not super comfortable but it’s on details. This guy is so smart. Who am I to criticize him? Number one is exercise. You can see that, by far, exercise is the thing that you need to do.

Peter Attia says type 2 cardio and zone 2. It’s important to balance, doing a little bit of Peter Attia, and something that you need to take care of. That’s the most important, diet and have some calorie restriction that’s acceptable for you. It’s not a diet for six months. It’s changing your life. You have a diet so you can live a long time. There’s that calorie restriction. You can do caloric restrictions in so many ways.

You can do intermittent fasting. I like to do intermittent fasting because it helps me to do caloric restriction automatically. There was a very interesting paper when they were published in ARDD. They coupled caloric restriction with intermittent fasting, the synergy, then you have the maximum extension of your lifespan.

Diet is very simple. With diet, the most simple is to stop drinking alcohol. It’s very difficult. If I say we should drink zero alcohol, I’ll break the rule of communication number one, “Just say what people want to hear,” but alcohol is a poison. It has been socially acceptable because before water was a poison. You will get an infectious disease, so the safe choice is alcohol. We built an entire culture around alcohol and it’s a beautiful culture.

When I meet people and we can talk about those wines, it’s just the culture. There are people who can talk about how our Federal does its backend. It’s the same sophisticated culture. Anyway, alcohol is a poison and it’s a very potent poison because we are made of fat and water. Alcohol has this unique ability to go through fat and water. It’s soluble in fat and water. It’s a poison that can go anywhere. The metabolite of alcohol is poison. The second metabolite is a poison.

It’s like, “I will take arsenic because in my culture, we love to take arsenic and it’s fun to take arsenic. I like the taste of arsenic.” People will say, “You are crazy. It’s a poison.” In 2 or 3 generations, they were so tolerant. They were doing all those things but you cannot have a kid celebrating without champagne. “Champagne is not alcohol.” It’s alcohol. It’s a poison. It destroys you.

I feel like that gives you a certain sense of authenticity in the fact that you are going to say something like that and you don’t care what the blowback is for it. I do think it brings up an interesting topic, which is lifestyle choices like alcohol and smoking. One of the questions that I have for you is that smoking causes methylation in DNA. Some of the epigenetic factors of aging. Your background is genetic. Tell me a little bit about the epigenetic factors of aging. Are the current modalities that are available looking at that? Is that going to be something that can be translated into a treatment?

We have DNA and we sequence DNA and say, “We have everything. We have the answers,” and then we discover that our DNA is not expressed in every cell. It makes sense. The hepatocytes should not have the gene that is necessary to make bones or something. You don’t want to have bones in your liver. In most of the genes, all the information is there in your chromosome. When the cells differentiate, and we come back to our Yamanaka factor discussion before, it goes down and you get differentiated, and the other genes are. With life, to close or to hide this DNA, the DNA will be linked with stones and you can manipulate and then it’s not expressed.

With life, when you have a double-strand break or something so that your DNA is relatively fragile, it’s a huge strand. It’s floating in the water. It’s fragile. It breaks all the time. We repair it all the time. Sometimes we repair it poorly and create some aberrant protein that is misfolded and stuff. We put a methyl group on it and say, “Under the rug, nobody sees it. Okay.”

The way that I explain it to my friends who don’t have a science background is that it’s like when you add these methyl groups to the DNA, you don’t have access to certain genes anymore. That might not be a problem. Certain areas of our DNA are not necessary for genetic information. There are certain areas that are and that might come out wrong, inaccessible, or whatever. It’s something that people want to know like, “I used to smoke and drink in the past. Is there anything out there for me? Is there something that can clean up my DNA per se?”

We come back to the Yamanaka factors. I will come back to Yamanaka to answer your question. Yamanaka factors, we use it in the lab. No problem. Every day we do organoids. In my company, we like to do organoids. It’s not the same as animal models in vivo but it’s also very interesting because we have human cells.

For example, when we do an organoid of the liver, we have stellate cells, pit cells, and hepatocytes. It’s not a perfect synthetic liver, but at least it’s human. When you couple that with studies in animals, you get some very interesting results because we extrapolate a lot from mice and we are very different from mice. If you take the skin of mice, the epidermis has two layers. Our epidermis has twenty layers. Something that does great things in the skin of mice will not translate in humans, but it’s true for a lot. Cancer research in mice has been sold in humans. We are far from that.

I was talking to a cancer researcher who’s testing flies for different effects. The point is that animal models are not perfect. Organoids are theoretically better.

Yamanaka, we use every day and everybody is now using those four factors scale. People said, “Why we don’t inject those?” It’s because aging is used by this accumulation of epigenomic change and a hepatocyte loses differentiation. With age, it becomes less and less hepatocyte. It becomes senescence. The tissue is not as good. Can we reverse that? It’s the question that your friends were asking and it’s the question that everybody needs to solve. People said, “Let’s inject OSKM in vivo in the living mouse, and let’s see if it’s getting young.” It should.

I get that question all the time and I tell them because it’s going to cause cancer. That’s what we are worried about.

Not only cancer but sarcoma, which is very bad, so you don’t. Now you have people like Jeff Bezos invested in Altos and brought those people. You have people all those great people who work on the reprogramming. The idea is not to reprogram up to iPSC but to do partial reprogramming. If it’s a hepatocyte, you go back to a young hepatocyte. You erase all the epigenomic junk that has been accumulated by life by random and that’s possible.

What people do to do that is first they put a doxycycline switch. With doxy, it’s on and off. You can put the on and off. It’s to be safe. Inject it into the mice. In OSKM, you have Myc or the M at the end. It is pretty much oncogenic. A lot of people said we should get Myc out. It’s still interesting to have Myc, but now the trend is to say, “O and S are important, Sox and Oct, whatever.” In the end, it is stimulated by making that. People try to look at different cocktails of growth factors. I mentioned the work of a guy who is adding two factors and it could be these multiple factors. You can do multiple combinations. The idea is to erase that but not to go up to iPSC, just a little bit.

It will take time because you have to switch. The fine-tuning is very difficult and it’s not easy. AI will play a major role in that because there are a lot of people who are evaluating a lot of combinations. When you have multiple combinations, you switch. It’s exponential and it’s so difficult. The partial reprogramming is the way people want to go. Partial reprogramming is extremely interesting. One consequence of partial reprogramming is you cannot have partial reprogramming for the entire body.

That’s quite interesting because you want the hepatocyte to go back, but if you test the hepatocyte, what makes the hepatocyte go this way? If you take the thymus, maybe the thymus will not move because the thymus is an organ we lose after 40. More or less, our thymus is not functional. It ages faster. All the cells are not aging at the same pace. The thymus is very important because if you want a T-cell to become a memory, they have to be activated by the thymus. When you are over 40, you don’t respond well to the vaccine because your T-cells are stimulated, but they don’t keep the memory because they are not being activated by the thymus because your thymus is too old.

If we could rejuvenate the thymus, the immune system would be a huge problem. Very difficult. When I say immune system, I’m talking about 36 different cell types like B-cell or T-cell. What about the microphage? It’s all different. When I say the T-cell, are T4 and T8 the same? This partial reprogramming has to be tissue or at least organ-specific.

It also makes the research very interesting. We understand the biology of aging and cancer. We know that cancer is here. The biology of aging is even more complex. There won’t be one company. People want to invest. Very often people ask me, “Should I invest in your company? Do you want another company? What company?” I said, “Invest in a lot of companies because there won’t be one company coming with a silver bullet.”

Invest in a lot of companies because there won’t be one company coming with the silver bullet.

It’s going to be a combination of many different things.

For cancer, Celgene will be the company that will develop all the cancer or solve the problem of cancer. No. There are multiple companies and there will be multiple winners. In aging, there will be the same thing. There will be multiple winners. When you say partial reprogramming, would you be coming from outdoors? It will come from a U-turn bio. It may come from multiple people and multiple angles.

We should be very careful in the research because it’s so rich. Some people will come with the AI angle. Some people will come from the reprogramming. Some people like us will come from, “Let’s take the problem at its source.” The issue is we have DNA damage. We poorly repair DNA damage. We create this epigenomic. Let’s take genes that are regulating this epigenomic change like Sirtuin 6. Let’s try to find a better Sirtuin 6 to better regulate this epigenomic change. That’s a different angle.

There are some people who will come with a smaller angle like unity who will say, “It’s all about senescence.” Senescence we understand and we don’t. We just start to understand senescence. A few years ago, senescence was bad. All the senescence was the same. There are good senescence cells and bad senescence.

I’m very familiar with that aspect. I did want to talk about your target, which is the gene therapy for Sirtuin 6. Less so for the theory of you fixing aging, but for genetic disorders in general, let’s talk about gene therapy for a second, which is one of the things that I told you I wanted to talk with you about. My background is craniofacial genetics and the idea of a disease like cherubism, which is where these young kids grow tumors in their faces to the point where they look like a cherub, which is why they call it cherubism. I know the gene, the protein that it expresses, and the end product which is the cherubism.

I was talking with another geneticist and I was like, “Why can’t we fix that? We know all the steps in the process. Just fix it.” She was saying that gene therapy is controversial because, in the past, there were certain kids that tried to fix their genetic disorders and they had poor outcomes. Some of which was death. That’s something that’s out there in the social fabric of academia. Number one, my question is, is the stigma with gene therapy changing? Number two is, are we in a different place from back then technologically that some of those things, we are not going to make the same mistakes? The stigma is overblown.

The answer is yes and yes. Stigma is still there. What we call gene therapy is such a big bag of different things. In the example you mentioned, you want to do gene replacement. First, we had viruses and that will also answer the second, is it evolving? For gene replacement, we used to use lentiviruses, mostly viruses and we were inserting to the chromosome. The insertion was random.

You were lucky, you were not inserting into a gene that’s super important, but you could insert any and create a lot of problems. Now we can have better insertion and localization, so it evolved. The problem was gene therapy is such a big bag that we should find a different world because gene therapy means nothing.

It’s like cancer. People say cancer, but breast cancer is different from prostate cancer. We have prostate cancer with a chance to die from it. It’s slowly progressing. Breast cancer is all the same. No, you have HL2 positives. They are different beasts. The same thing with gene therapy. First, there’s the gene that you can deliver and insert into our genome. There are ethical concerns. You insert it in the somatic cells so it won’t be passed to the germline, but it’s still there. You cannot remove it. It’s off-target. It’s difficult.

Now we have tools like AAVs that allow us to not have insertions. The AAVs go into the nucleus, but it’s not inserted in one chromosome. It’s an extra chromosome. It’s a transient expression. The nucleus, at one point, will get rid of the additional gene that you bring, but in terms of safety profile, it’s much more acceptable. Now gene therapy is progressing so fast. It’s the same issue with longevity that the science is progressing so fast these days and it’s exponential when the mindset of people does not progress expression at the same pace.

We still run for breast cancer but would people do a marathon for HL2 positives? It will be a little bit of breast. No, they want to have the pink thing, just lady only. Thinking about cancer with an organ mindset doesn’t make any sense now, but the mindset is still there. You can mobilize. It’s the same thing with gene therapy. It’s a major problem because of the pace that the science moves. It’s so fast. In longevity, we have so many people now who are excited. There’s money going there. There’s the brain.

You had first pioneers like Aubrey De Grey, David Sinclair, and people you mentioned like that. The first people said, “This guy will use his tenure. His tenure at Harvard and longevity. Do cancer like everyone. It’s safe. Enjoy your tenure and don’t make waves.” Those guys were taking risks. Now, there’s no risk. Everybody is like, “We should open a longevity lab, and every university has a longevity lab. There’s a lot of money.” The pace of discovery is going on the other hand. My neighbors or people who are not in the medical field or the longevity field still think, “We have always been aging. Why do you want it? It’s just Jeff Bezos who wants to live 150. It’s a caprice of a billionaire.”

People are hesitant about it. I was talking with somebody, I was like, “Wouldn’t you want to live to be 150?” They are like, “No. I’m okay.” I’m like, “What?”

People will see. You ask first, “What is old?” When you do a survey and you ask a 30-year-old, what’s old is 60. If you do the same survey and take a sample of people aged 60, they say it’s 80. It’s always moving. They are right because what do they see? They see people who cannot move, who are sick, and who leave their minds. They have Alzheimer’s. They are like, “Do I want to stay like this for 30 years additional?” That’s not a gift. They are smart. They understand.

The problem is that they are not aware that they could have 30 years of rich life contributing, but the mindset right now is they are old. Your brain is not functioning as well as fast. “That’s the new iPhone 16. You are too old for that. You won’t understand. Only the kids will understand.” It’s not true. It’s a question of mindset. If people understand that they can stay else, everybody would like this. If I can run a marathon and keep my ranking in tennis when I’m 150 or play the ITF 140 or 150 category.

Everybody would want that.

You have a lot of chances to beat him one day. Yes, I get that. Do I want to live 150 to go from my dialysis to my chemotherapy, and I forgot my re-education for my stroke because of Alzheimer’s? No. That makes sense. The mindset is wrong. It is because the general population does have this information. When they say, “I’m not interested, that makes perfect sense.” We need your show to explain this. That’s so important. Change your mindset. You should not accept this cognitive decline and this loss of muscles. You should be able to keep your muscles and be able to walk. Getting old doesn’t mean you have to have a walker.

It doesn’t mean you need to give up on what’s considered to be a healthy lifestyle either. I feel like I could talk to you for hours. I do realize that we are coming short on our time, so I wanted to make sure that I finish up with the same three questions that I ask all of my guests. The first question is where do you see this space in ten years? I feel like that’s a loaded question because everybody has difficulty gauging where their space is going to be in ten years, but where do you hope that this space goes in ten years?

You talk with Aubrey. He is much more optimistic than me. What we will get for sure in the bag is there’s the repurposing of drugs. There are people like Nir Barzilai and Brian Kennedy in the US. They repurpose drugs. Within ten years we will have rapamycin, metformin, and AKG. All those existing drugs will be there. They will be approved. We will have a marginal benefit with that.

There’s progress we can expect from people who go for gene therapy, senescence, and mitochondria. It’s a huge topic we didn’t talk about. Within 5, 6, or 10 years, we can expect to have products that will bring higher benefits than the monumental benefit you get from repurposing drugs. Repurposing drugs makes sense. It’s cheap. Metformin in low doses is perfect for me. People like Nir Barzilai and Brian Kennedy are paving the paths to lead other people. We will see things in senescence, gene therapies, and mitochondria. We will see with AI some intervention in the microbiome also.

We need the deep learning on that. We need the microbiome ChatGPT. People are already working, fantastic people. We will get something in ten years. We will start in ten years to see partial reprogramming. I don’t think you will see one injection and it’s like, “Now I look like 25.” We will be able to take a thymus and get a young thymus. My company research on NASH. We can regrow the liver. There are a lot of people who have damaged liver with fibrosis.

People love alcohol like we talked about.

NASH is non-alcoholic. It’s fat. Thank you, Coca-Cola, twelve million people are estimated with NASH in the US. It’s the leading cause of liver transplants. A liver transplant is not fun if you can find something. In ten years, we will have that. A little bit of reprogramming, but it will be very specific on organs and things like this. We have seen David Sinclair present something with the optic nerves. He is now publishing amazing things with small molecules.

It took the work of a lot of people. A lot of people try to find some other way than going with aggressive growth factors. That also could be interesting. That could lead to some discovery. We can be reasonably optimistic that we will get huge benefits. I’m already 66 and I think I will get some benefit in terms of longevity.

That brings me to my next question. I asked Aubrey the same thing. What are you doing in your own life that’s available right now that maybe somebody might not know about? Aubrey says he’s not living his life any differently. He’s just waiting for the technology. For me, I’m trying all of the exercise techniques that Attia wrote about in Outlive. I’m also doing sauna. I’m also doing cold therapy and things like that, but what are you doing in your own life? How have you changed your lifestyle at all?

I have a different lifestyle and lifestyle change can be relatively impressive. I do a lot of exercise and I’m extremely disciplined. I’m doing that regularly. When exercising, it’s not only the cardiovascular, the weightlifting, and the balance. That’s a combination. Peter Attia seems good. Diet is very simple. I do caloric restriction through intermittent fasting. That’s still very good and it’s very acceptable for me. I will not recommend it to everyone.

What is your window like? For me, I usually have my first meal around 1:00 PM and then my last meal around 8:00 PM.

The same. My feeding window is eight hours, so I do a little bit more. I do noon to 8:00 and it’s an 8-hour window feeding. It was said that it’s okay to have even bigger windows. It’s interesting not to have your mTOR stimulated and your insulin not to be triggered too much. I don’t want to spend too much time on that.

I would love to spend more time on that.

Circular sleep. I’m super careful. I have to travel and I pay a lot of attention in my sleep, and social interaction. I try to get as much social interaction. I do sauna and the cold shower. I never take a hot shower. I take a cold shower all the time and all are interrelated. You mentioned the sauna and the cold shower, those influence your sleep.

If you stop eating at 8:00 and go to bed at 10:00 or 11:00, you will have a better sleep if you eat until 5 minutes before you go to bed. I separate to be discussing it with you but in life, it’s interacting. I try to avoid supplements as much as possible. I need to have a very strong rationale. I’m part of a longevity group and I see people who take something like 20 or 30 supplements. By training, I did urology surgery and nephrologist. I’m a nephrologist now and board-certified. I see so many people who had drug interactions and it’s very complex. When you take twenty supplements, you don’t know what you are doing.

It’s not FDA-regulated. I feel like there are so many things that I want to talk to you about, but we don’t have the time for it. You should come back. This was an interesting discussion. I feel like even this question, both of us could talk for an hour about. You should come back to the show if you want to. If you are ever in Boston, you should come here. We’ll do it in person.

The chairman of my company is in Boston. I have some board meetings in Boston and I love to work to go back, but yes. It was very nice. I like the show.

Last question because everybody gets three. I don’t want you to shortchange me with two. The last question is I draw a lot of inspiration from science fiction especially when about the future. I think of utopian visions of the future. That’s something that I think about to propel me to do some stuff like this show and to be an excellent surgeon every day. Those are the things that propel me to do the stuff that I do. What are some sources of inspiration that you have? If it’s science fiction, that’s great. It doesn’t need to be science fiction though.

I love science fiction. It’s a very interesting genre. It fits with my nerve personality. “What if?” is what we should ask every day. What if it was different? We take for granted that it is like this but it could be different. What if? Is that what science is about? It’s not science fiction. In science fiction, we are talking about the huge gap between the progress of science and the mindset of people.

There is a huge gap between the progress of science and the mindset of people.

I think that science fiction plays a role in that. You heard that I’m French-American. I was raised in France with snow white. When LJ drew that travel to the moon, the rocket landing didn’t exist, but when I saw the real moon landing from the US, I was prepared by that. and there are so many good science fiction writers, but I would love to see very good writing about longevity so that people will get slowly accustomed to the idea. They’ll say, “I read that in a book. I saw it was pure science fiction, but now it’s science,” and then it helps. You read the submarine and then people say, “Yes,” when it did not exist. It opens your mind and it’s fun.

Thank you so much for speaking with me. Thank you to everybody who’s tuning in out there. Please like and subscribe. Thank you, guys. This was a fun conversation. We will see you in the future. Have a great day, everybody.

Thank you.

Important Links

• Eric Leire
• Aubrey De Grey – Past episode
• Outlive

About Eric Leire

Dr. Eric Leire is the CEO of Genflow Biosciences, a longevity gene therapy biotech listed on the London Stock Exchange. He also serves as the executive chairman of Immunethep (virulence company) and as NED for Pherecydes (anti-infective), BSIM Therapeutics (CNS) and Inhatarget (oncology).