#419: A Mind-Blowing Mitochondria Episode— Mito Transplant, Rare Diseases & Biomarkers With Dr. Natalie Yivgi-Ohana

Welcome to Longevity. I'm your host, Natalie Nidom. I'm a nutritionist, a human potential and epigenetic coach, and I created this podcast to bring you the latest ways to take control of your health and longevity. We cover it all from new technology and ancestral health practices, to personalized interventions, and a very special interest of mine, peptides and bio-regulators. Enjoy the show. Welcome back. I'm Natalie Nidom, your host, and I have to share a secret with you guys. After I recorded this episode, my mind was so blown, I actually had to take a break. I had to step away. I had to reboot my brain. It was like literally blew my mind. And this is such an incredible topic. And the truth is that I have this incredible privilege of speaking with world-class experts across every corner of Longevity. And every so often, a conversation comes along that just truly expands the way I see how human health is going to be impacted by some of this new technology that is as old as humanity itself. So this is exactly what happened with today's guest. And I literally couldn't wait to share this episode with you. Dr. Natalie Yivki-Ohanna brings an extraordinary depth of knowledge on mitochondria, those incredible little organelles, breaking down how these tiny powerhouses influence fertility, hormone production, immune function, and even the aging process itself. We also explored the emerging science of mitochondrial transfer. And what this could mean for the future of Longevity medicine. And they're already applying it to areas like neuro-degenerative disease, fertility, rare diseases. It's really like, you guys are going to love this because I know you guys and I know you're going to love this. Let's dive in. There are some good tools in Longevity. 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You can say 15% at bioptimizers.com forward slash bio NAT and use code bio NAT for 15% off any order. Look, it's not about knocking yourself out. It's about supporting your body in the way it was designed to work. Welcome to the show, Dr. Natalie Yiggi Ohana. It is such an honor to have you here and thank you for taking the time to speak with me today. Thank you so much. It's a pleasure to be here. Believe me, a lot of people are going to be excited about this, including me. So we're going to talk about the tiniest little structure in the human body, I think, or one of them. It's not the tiniest because it's got tiny things inside of it. But the mitochondria, what we talk about the powerhouse of the cell, which I think it's such a hot topic and has been in many ways gets reduced to less than what it is. But this is your career. This is what you've built your career around. So when did you decide that mitochondria was going to be your topic? I think my two-chondria actually decided I'm going to leave this new. I'm completely controlled by this organism and fascinated. And it took a while. I mean, I started as an embryologist, so I'm an expert in Invitro fertilization. And I started to study the role of mitochondria and embryonic development. And I was fascinated by the fact that actually mitochondria only inherited by the mother. And then if you we do an Invitro fertilization where we inject the sperm with the mitochondria into the old site, eventually no leftovers of this mitochondria out there. It's only maternal and it is selecting against the paternal mitochondria. So that's like it's enormous. And there is a huge responsibility for us women to transfer this mitochondria to the next generations. I have four daughters, so they will transfer my mitochondria. Yeah. That's incredible because and I mean, obviously we know that the ovaries are so dense in mitochondria. Yes. Right? Like which makes sense on the fertility side. Yeah, but very important because there are so many supportive cells and tissues within the ovary to make that one special all size every month to fertilize. And also when we go through first the puberty and then the menopause stage, what is the role of the ovaries and the hormone production in mitochondria aspects of it? So when I started my PhD, I was walking actually an oil reproductive organ systems and mitochondria. And the fourth role of mitochondria that I learned about is of course energy production. We'll talk about it greatly in a minute, but the role of mitochondria in steroid hormone production. So I don't know if you know, but the first hormone that is produced is produced in the mitochondria. And I studied a protein, the transfer cholesterol from the outside of the mitochondria into the mitochondria, where an A enzyme converts this cholesterol to pergnenolone. Pergnenolone is now the precursor of steroid hormone production, all sex hormones. I mean all glucocorticoid and mineralocorticoid and the sex hormones, all of them start in a process in the mitochondria. And when mitochondria dysfunction, of course, you get distracted hormone synthesis. So it's super critical. There is no life without all these hormones, of course, in the production of hormones by the mitochondria. And there is no use in living, right, without sex hormones and what it does to our bodies and to... Well, to everything. I mean, look, you've just blown my mind and I'm sure a few others, cholesterol is used in the mitochondria. Like all these people, like this race to the bottom on cholesterol as we age, which ultimately could be, I mean, I don't know for sure, but I'm not saying, but which could ultimately be feeding into the pathways that lead to the aging process and decline, not to say we have to run around with high cholesterol, but... It's an important role for cholesterol, both in building our membranes, of course, and... Oh, of course. We could drafts that are important with cholesterol inside them for signaling within the cells and outside the cells, but also for this very important task of steroid hormone production. You cannot do that without cholesterol. That's incredible. So was there a not-ha moment when you decided that, you know, when you're like, okay, okay, medicine is completely underestimating mitochondria. I'm going to do something about it. Yes, so there are two ha moments. One was I was doing my PhD on this life creation with mitochondria and the fact that they produce energy and steroid hormones and there is no life without them. And then I did my post-optolyphaloship on triggering cell death through... through the mitochondria. So if a cell has a damaging response, mitochondria immediately, they behave like these smart bombs and they release that start and cell suicide mechanism that is irreversible. And then that was the first aha moment. I said, life and death controlled by the mitochondria. And that's where I should focus my my next life on. That was the first aha moment, really realizing how important they are. And then the second one came after I finished my on my academic training and I decided that there is such a huge and mechanized in the whole field of mitochondrial dysfunction that the problem was that no one could really say whether someone has a mitochondrial dysfunction or not because there were no methods to measure that. And then again, we are all going to suffer a mitochondrial dysfunction as we age. So age is a kind of mitochondrial dysfunction. I said, no one treats it today. There are no therapies to fix mitochondrial dysfunction. That's where I am going to spend my life on. And I said at home for like nine months, just thinking and I read all these books and all and I went back to the early days of how mitochondria will well identified. And there was the Lynn Margolis. Lynn Margolis was a great scientist. She was a woman in the 1960. She tried to publish her endosymbiotic theory meaning okay. So tell us about it. Get tell us about that. Rejected her publication about the endosymbiotic theory that we all know today. This is a consensus. Absolutely. mitochondria used to be bacteria, independent bacteria that entered into the cell during the evolutionary process. So one and a half billion years ago, the cells started to develop. No clue is what's in there yet. It was just DNA flying inside the cell. And now this bacteria enters into the cell. Usually when a bacteria affects a cell, they will multiply until they kill the host and then they will live to infect another cell and so on and so on and so forth. In this case, mitochondria entered into that cell but they did not multiply until infinity just a little bit. And then they actually became an independent part of the cell and they transitioned most of the DNA into the nucleus and maintained just a portion of it within the mitochondria. Now they can no longer live independently. They have to reside within the cell and this is some symbiosis. What the mitochondria did were actually enabling the cell to survive in an oxygen and rich environment which is what we have here on earth, right? It's an oxygen and rich environment and before that oxygen was toxic to cells but now mitochondria consumed the oxygen and the nutrients and produced energy for the cell. And this is not cheap. This is a chemical molecule that is required for everything that happens in the cell. It's called ATP or a denosine three-fourths-files and this is a chemical molecule that is needed for everything the cell is doing. Every pump, every enzyme, every protein formation, nucleotide formation, every DNA replication, everything requires this ATP and that's how life began. And now there are creatures on this planet that consume oxygen for this energy thanks to the mitochondria that we have residing within ourselves. My aha moment, the second one that I promised came when I suddenly realized that actually mitochondria were very selfish. They behaved like a selfish gene. They wanted to integrate their DNA into the nuclear DNA to protect it and now the nucleus produces most of the proteins for the mitochondria and this is a perfect symbiosis. And this is why I love it so much. My aha moment was can we use mitochondria to fix diseases? Can I integrate mitochondria from one cell type and apply it to another disease cells? Will they go in? Like they did you in evolution? And that's it. That's how we know we started. It was crazy. I just had to test it and it was true. Wow. So what was that scientist name you said in the 1960s and who didn't publish her paper and who ended up? Was it a guy? So Lin Margolis was a scientist in the 1960s and she suggested the fact that there were endosymbiosis happening between different species. It is also the chloroplasts inside plant cells which are also evolutionary. They used to be also germs and the mitochondria in in our living cells. So she suggested that there is a structure that enforces these two species to come together in order to supplement a missing function. That missing function was the use of oxygen and the outcome was the creation of the energy, the ATP. She tried to publish this in 15 different journals and she was rejected in the 16th time that was accepted and eventually it's a common practice for everyone. This is the endosymbiotic theory. When you look at the mitochondria and the microzov microscope, they look like bacteria. They are devised of bacteria. They contain your own DNA just like bacteria and their DNA is circular just like a bacterial DNA. Everything about them says the del used to be bacteria. They actually can replicate independently from the cells multiplying. They do the fusion and mitochondria biogenesis and they are very independent within the cell. I love mitochondria. I think they're the cutest organelle personally. I'm surprised you don't have a big poster on your wall. I have the mitochondria there but I have the wall over there. I'm sure you do. You're going to have to get mitochondrial jewelry and stuff. I have my bag. I have a mitochondria jewelry, actually a very special stone that was brought all the way from Africa, from Ethiopia and then an artist created a mitochondria for me from that stone. I actually should have buried that. One of my partners actually created that jewelry for me. It's beautiful. I will show it to you when you come to these. Let's talk about how understanding this endosymbiotic origin of mitochondria. How should that affect how we think about chronic disease? Does it come into play in terms of how we're thinking about chronic disease? It's so interesting what you said earlier that you've got these incredible branches like fertility, chronic disease, and mitochondrial disease specifically, but just any chronic disease. Then just the pure process of aging. When we're talking about chronic diseases, does this endosymbiotic origin of mitochondria have an impact on how we need to be thinking about it? Of course. The first thing, of course, the fact that they are consuming oxygen and using the nutrients that we need to produce the energy, we need to be mindful for the quality and the amount of oxygen that we are breathing, of course, and how important it is that. It's not wondered that when we are doing sports and when we're doing yoga and we're singing, we're just loading our bodies with oxygen that makes us feel good. That feeling good is actually boosting our mitochondria with energy and eventually that's the outcome. When we are feeling our mitochondria, there are huge differences between if we are absorbing carbohydrates, glucose, for example, all if we are now feeding our mitochondria with free fatty acids because you know that the number of molecules of energy that you produce from a carbohydrate versus from a free fatty acid is completely different. You can get up to three or fourfold higher numbers of molecules if you consume free fatty acids versus glucose. I think the mindfulness of what will cause our mitochondria to be more active or more efficient in energy production, this is supercritical. We all feel the drop of energy and the start of frailty as we age. We know that in chronic diseases people feel weak, they are less active. How do we know that? This is mitochondrial dysfunction, eventually. We feel the lack of energy, we feel tired, we feel exhausted. This is practically mitochondrial dysfunction and why is it happening? Because mitochondria carry, as I mentioned, their ancient DNA that came from their bacterial origin and that DNA is circular and exposed. It doesn't have the three-dimensional structure of our nuclear DNA with all the proteins that are protecting it and it is very, very protected. It has to unwind to work. There are systems to fix errors within our nuclear DNA that doesn't exist in the mitochondrial DNA. The fact that it is open, very sensitive for the environmental insults and that there are no machineries to fix damages in the DNA of the mitochondria. I want to cause it to be very, very prone to mutations in the mitochondria. Now, each mitochondria have multiple copies of mitochondrial DNA and in each cell you have many mitochondria, so even more copies of mitochondrial DNA. Sometimes if it's just several of these are mutated, you won't feel anything. But with time, the process, the natural process of selection of the good mitochondria is harmed with the age. This is the microobotus, so it's going down. What you see is accumulation of damaged mitochondria within the cells and those mutations in the mitochondrial DNA accumulate more and more as we age. Those mutations are what causes us to produce less efficient energy and eventually, even more reactive oxygen species because of the non-efficiency of energy production and that further circulates and increases the damage within the cells all eventually connected to mitochondria and their addiction. So that's the origin of why chronic diseases eventually evolved from this DNA. It is so sensitive to delicate. It's interesting. And really speaks to anything we can do to, which we can talk about later, what are the things people can do to support my topology, mitochondrial biogenesis, like to what are the things we can do to do that? But I want to go back to something that you said earlier and you talked about the difference in ATP production between glucose as a substrate, fuel versus free fatty acids and ketones. In that, and I don't know if you have, do you have a position in terms of whether people should follow more of a ketogenic diet in certain states or does this more speak to maintaining metabolic flexibility so that the body, like the problem is most people live in sugar burning, 1900 percent of the time, right? Because they taste good, they make us feel happy. And the worst part is when we get sick, we go there, because it makes us, it gives us, I mean, I've just gone through something. I can tell you, I've probably eaten more carbs in the last month than I have. We do that in the last year of stress, right? And we feel bad. You want to? Well, because of the cortisol is high, my adrenals are taking a hit, you know, like I feel like going keto right now might not be smart. But maybe that's a trick. Maybe I should be thinking more on the keto side. And I'm just curious, and if you have an opinion in these chronic diseases or in these situations where the mitochondria is really impaired, is there an argument there that says that either introducing the right exogenous ketones at the right time or maybe following a ketogenic diet might be, this might be a use case scenario for it. Yeah. I think it's a genetic diet that's a very dramatic and very drastic, yeah, as the, they're problematic, like they're not perfect. Yeah. And I think we should, but definitely I do believe in the concept of more free fatty acids versus carbohydrates. There is a very simple explanation to that. This is why I'm so strongly believe in that. What happens is that when we consume carbohydrates, our cells immediately, there is a huge responsibility to remove the glucose from the blood, right? You cannot stay around. That's what we want. Once it goes into the cells, it becomes a source of energy. Okay. And then it will create ATP in a non-efficient way, but through the glycolysis, you will actually get ATP produced. You'll get about nine, nine molecules, I think of ATP. And then if it goes into the mitochondria, you will get 36 molecules of ATP. If it goes through the mitochondria, if the pyrovert goes in. So the responsibility of removing the glucose from the blood and now creating energy through the glucose is a huge. And if you consume both free fatty acids and glucose in your diet, and you know it's a hamburger, okay? With with the bun and the cheese and the burger itself. So you have it all mixed in. What the cell will do, it will use the carbohydrates for energy production. And the fat will go being sold because they don't need it now. They have enough energy from the carbohydrates. If you eliminate the carbohydrates from your diet, now you are educating your cells that they need to use the free fatty acids in order to produce the energy. The cell will multiply the mitochondria to the amount needed to face the flow of free fatty acids that you are now consuming. And then they will not be stored. What happens is you are currently, when you start a paleo or a ketoday, you are educating yourself, your cells now, to increase the content of mitochondria. So they can face the amount of free fatty acids that currently are consumed. They will not be stored. They will actually start using your fat tissue because they don't have the glucose now. And there is a requirement for energy that is coming from the fat. And this is why this re-education actually shifts the balance and people start to lose weight. And it's crazy. It's completely against what we are being taught. However, there is the carbohydrates that you have to consume through vegetables. Of course, there are carbohydrates everywhere. When you are doing ketogenic, you have to cut on everything. And that have their consequences because you need the vitamins, you need the fibers. This is why paleo is more of diet that I believe in because it's not about natural food, consuming good free fatty acids and vegetarian. So it's mostly nuts and avocado and olive oils and butter, which is great and coconut oil, etc. Those are good free fatty acids that supply me with great energy and very low cowbdyes. And it is about metabolic flexibility. It's so interesting to hear you speak this way because it really reinforces in me this idea that if you are heavily on a car, if you are on the glucose, pure the head of the glucose carrying parade, that process of re-educating yourself. Because your cells know. It's almost like the factory has been shut down for however long. And so now we need to restart the machinery and it can be ugly at the beginning. But if we can get to that world where we can kind of flip back and forth, it allows us to get to the best of all worlds. Going back very quickly to the, and we're not going to stay on endosymbiotic any for much longer, but can we talk a little bit about this symbiosis influence? How it would influence modern immune signaling? Because the immune system, we were talking about this offline earlier on another subject. Again, we don't think of it as a mitochondrial issue. As foundational as mitochondria is to the cell, proper immune balance and function is foundational to our ability to be healthy and age well and not have chronic disease. So I don't know how many people know that, but the function of immune cells really depends a lot of mitochondrial function. And actually the different cell types that we have now blood in and out in your system also differ in their mitochondrial function, they differ in their mitochondrial content, number, quality. So it's very different. So for example, if you want the cell to stay in a stem kind of senescent state or quaisant state, the mitochondria actually not active. They only rely on glucose for metabolism. Once the cell needs to differentiate to different cell types, then they start activating their mitochondria. And now different types of cells will carry different amount of mitochondria. And actually they are controlled, their differentiation state, are controlled by the function and the number of mitochondria within those cells. So it's really critical to have good and functional mitochondria in the stem cell that will eventually produce all the immune cells that are acquired. When there is an immune requirement, in the body, there is a pathogen that is inflated in your, whatever, then the mitochondria needs to be very active. And this function is being tested. An antigen producing cell needs tons of mitochondria. Okay, this is a fundamental requirement for the production of antibodies or the presentation of antigens, all requires energy and a lot of energy. So the function of mitochondria actually fundamental for the immune system function and very, very important. When we talk about immune function, it's not only about protecting the body from invading pathogens, it's virus or bacteria. It's actually protecting our tissues from damaged, damaged components. For example, while we are aging, there is an increase in the presence of cellness and cells. Those cells, like dormant cells within the tissues, the fact that they are there, not functioning just there and secreting their factors is a damage in response. What should have happened? Right. Is the immune system should have come to that organ and clear them away? Because the immune system is not functioning. Well, you get them accumulating within the tissue and inducing further, further damage. So the function of the immune system is not only against foreign pathogens, it's also against damaged dead cellness and cells within our tissues. They have to be removed by the immune system. So there is a very strong connection, for example, between immune dysfunction and Alzheimer's disease, immune dysfunction and metabolic diseases, pancreatic diseases, kidney insufficiency. There are many connections between these two organ systems, the immune and further organ infection mediated by mitochondrial dysfunction. And you had mentioned earlier before we started recording, you had mentioned something about the immune cells started over producing mitochondria or they start over replicating. I can't remember. Yeah. So it's really the pattern, the type of the cells that are produced because the immune system is composed for many, many different cell types. And eventually the type of cells that will be produced is dependent on the mitochondrial content and function and special characterizations of the mitochondrial within that cell type. When immune function is overactive, when you see the real function over at the autoimmune disease or it might be due to impaired mitochondrial function in a certain cell type within the immune system. Okay. It's important to look also on the specific cell types. Yes. The headline that people know, if anybody knows about mitochondria, they know that they produce energy, right? That's going in position. But you, I think you and many other scientists talked about the micellular sentinels. They also sense the environment. They also make decisions. They also communicate as a warning, early warning signal in the cell. Like, you know, like they sound the alarm. Basically, like, can we talk a little bit about how they sense the environment? What are the other things that they're sensing for? There is a close relationship between what happens in the nuclear environment and the mitochondria. The sensing that we talk about is mostly environmental sensing. For example, the nutrients or the oxygen that currently exists within the environment of the cell. And then the mitochondria sends signals to the nucleus. There are many proteins that are on the mitochondria in their day-to-day job. And then when there is a stress signal, they will ship that protein into the nucleus signaling that now the nucleus needs to react. What does it mean to react? The nucleus can now induce gene exploration of proteins that are required to stand in stress conditions to allow the cell to be more active in certain directions versus others to eliminate reactive oxygen species or to increase the number of mitochondria. That's what needed. I've just said, for example, when you are controlling the nutrients and now there is more quifati acids, you need more mitochondria. Let's restart mitochondria genesis. If there is now a reduction in the needs of energy, let's start mitophagy and eliminate some of the mitochondria. All of that is a crosstalk between the mitochondria, the environment and the nucleus. It all goes back eventually to gene expression and protein production, etc. So the mitochondria behave like sensors. There is something very new recently in the past few years that speaks about mitochondria also a sensor in organelles between cells. So now is a phenomenon known as mitochondrial transfer. Cells can produce this tunnel in nanotubes like tunnels between cells and they can transfer mitochondria to neighboring cells. Come on. I think we're going to see. I know. This transfer is actually induced by stress coming from the cell that is in demand. So one of the stress signals is that I don't have enough mitochondria. I have a dysfunction in the mitochondria and now the donor cells will create those nanotubes and transfer the mitochondria to the demanding cells. We see that in cancer between immune cells transferring mitochondria into cancer cells. The cancer is using this mechanism to actually extract mitochondria from the immune system in order to walk in a more efficient way. This is maybe a mechanism of how in the future. We will target cancer and try to cure. That's why. Wow. Element we see transferring mitochondria in the brain through microfages from the immune system, transferring mitochondria into microglia cells in the brain and rescue in function. There are many systems where mitochondria's function. My mitochondria transfer have been shown and it is a pure signaling between cells and it's beautiful. So that's incredible because that's almost like in a healthy cell or in a cell that's not fully broken yet. It's an emergency that says I don't have the energy to make my own new mitochondria. Can somebody send me some over so I can survive? That's right. And then if that doesn't work then I guess at that point that's when the cell would eventually become a senescent cell and become a more damaging cell. But how do you shut that down for how do you shut that pathway down for cancer and not for the systems that needed I guess is then. That's a million dollar question. I had a question here and I think we can now establish that I at least from your work and from everything I'm hearing you say we can say that when it comes to chronic disease it's less of a chicken than the egg thing. It's probably starts with mitochondrial dysfunction versus mitochondrial versus the mitochondria's dysfunction as a downstream effect. Although my guess is once you get into that spiral it's it doesn't matter anymore but the way to fix it is going to go through the mitochondria. Yeah. So can you talk a little bit also about how mitochondria communicate danger to the rest of the body? You talked a little bit about it at a cellular level. Is there another mechanism that is more macro or does it all happen kind of through the nucleus, the genetic expression? Is it basically that process? So there are actually also messaging of mitochondria between cells that are usually delivering stress response or damage responses. Those are called exosomes so cells usually secret content from the cells and they contain fragments of mitochondria and those exosomes are secreted out of the cell and they are actually self-initiated signals to the immune system for example or to the brain. So there are multiple elements of crosstalk between the internal inside cell mitochondria to what happens in the environment. And it's not fully resolved and this is not my field of expertise but it is known that exosomes carry damaged mitochondria as a signaling to the immune system to say this cell is currently damaged and needs to be cleaned. Wow. Wow. That's wild. I mean guys, I hope you're geeking out on this. I'm fascinated. This is so interesting. Okay, let's move into mitochondria and rare disease and then I think I want to and then we'll talk about mitochondria and aging. So let's go to the micro and then we're going to go macro. So a lot of your work started with rare disease, right? Rare mitochondrial diseases. Do you want to describe a few of the conditions that you kind of, are there a few conditions you really focused on initially? Yes, yes, absolutely. So we started our our therapeutic approach is actually to harvest stem cells from the blood and then enrich them with mitochondria. We are doing this outside the body. So collecting from the blood outside the body and then enriching with healthy and functional mitochondria, those are blood stem cells. It means when they infuse back to the blood, they will engraft in the bone marrow and start producing healthy cells of the blood and the immune system. So the first disease that we looked into was an ultra rare disease that starts with a bone marrow failure. So the stem cells in the bone marrow, these patients are failing. They're mitochondrial failing and that means that the lineages of blood cell formation are disrupted and the disease that we started because we realized we first need to show that we can fix the blood system. What happened later on I will tell you, but the disease that we chose was a very special disease that first of all is not inherited from the mother. It's a genetic disorder that is not inherited from the mother and the patients are born with a huge deletion in the mitochondria genome. They are suffering of course from lack of energy and many other functions of the mitochondria, which means the first symptom is that they are not growing like their age match. So they're full failure to thrive and they have a bone marrow failure. And then we said if we'll harvest the stem cells from the bone marrow and we will augment them with mitochondria coming from their mother. It's actually an identical mitochondrial genetic source but without the deletion. That was the concept initially. It's not about the business model because there are only about 100 patients in the world with this disease. It is called pilsons syndrome. It's about understanding, can you, you're almost inducing endosymbiosis. Exactly. That's exactly what we are doing. Replicating what happened back there. But pilson is also a multi-systemic disease. When you see these children, they are all dying during childhood but as the disease progresses, it started moving from the bone marrow into other organ systems. So they start having kidney insufficiency. They start having diabetes. They have muscle weakness. They have neurodegeneration. They have cardiac issues. And when you think about it, they're just like an old man in a young boy's body. So it's just, it's a replication of the aging process in a very clean genetic background of a mitochondrial dysfunction. So we actually realized that this is the best disease to study the impact of our therapy in a multi-organ failure just like happens in aging. So without treating these children and what happened was that we improved more than just the blood function, just the immobilobino, red blood cells production. We started seeing that these children start getting more energy. And the children who were at six or seven years old in a baby stroller or in a wheelchair started walking and getting more energy, being more awake, more hours in the day, the kidney insufficiency stopped progressing. And that was, it was mind blowing. So we can actually impact with the same therapy that only enriches the blood stem cells with mitochondria. By the way, causing the immune function to be better. And now we see an impact on distal organ systems, on the brain, on the muscle, on the kidneys. So it was, you know, a disease where we can really learn so much about the potential of the therapy moving forward. So currently we are in phase two for these Pearson patients. And because it is so rare, so probably only a few patients to get us through the approval policies because there are just no more patients. But then obviously when we started, everyone looked at us and said, you're going to transplant mitochondria in aging, right? And then reverse aging. You're going to do anti-aging. And you said, okay, for real. Yeah. It's going to take a while. But the targeting of a very specific mechanism, which is the mitochondria, not by trying to improve one function because mitochondria have thousands of hundreds of functions, right? The complex. But by replacing the entire organelle, that was the approach that we took. And then we said, we have to be able to measure this. And as I told you, there are no blattest to measure mitochondrial function. So we developed them. And then we directly, those biomass, we could validate the biomarkers in the patients with the mitochondrial deletions and then tested whether before and after treatment, you see an improvement in mitochondrial function. So that was very important for us. So when we started, it was just this Pearson, with maternal derives mitochondria, and this is really non-scalable. When you think about us moving into aging, we can't really help mitochondria from our mothers, right? They are no longer a source. So we developed a bank of healthy, functional mitochondria that are actually coming from donor placentas. So women who give birth, everything within me, now everything is very female-oriented. So the mitochondria, only from the mothers, the donation of mitochondria comes from placenta, from women who give birth. We are female founders and more than 75% female in the company. Very, very female-oriented. But now we have a bank of healthy mitochondria that we can use across the board for anyone that will require this treatment. But we didn't go into aging yet. Because with the impact we see in children, because they are young and they are generating easily, going into an age-related disease and demonstrating impact also in elderly people. When we looked for disease where the bone marrow is failing, the stem cells of the bone marrow, and that was Nielo-displastic syndrome, MDS. And those are people that are 60 years old and older, and have a severe anemia, they are blood transfusion dependent. And the straightforward thing will do to improve their stem cell function and to see an improvement in anemia. And that was indeed what we started seeing. So this is currently in phase one and retreat patients. But those patients have other symptoms of aging, of course. So for example, one of these patients had the kidney insufficiency with blood creatinine that was high and he was already scheduled to start dialysis. And then three months after treatment, you start seeing a decrease in the creatinine levels in the blood. And currently he's on normal creatinine levels. So not only his blood improved and he is no longer blood transfusion dependent, also his kidney function improved. That's face it. You can't change your biology, but you can support it intelligently. A lot of products chase surface-level results while ignoring what actually drives resilience underneath communication. When signaling gets distorted by age stress or environment repair becomes less coordinated. And this is important and especially in skincare. Vitali understands this. They first earned by trust years ago with pharmaceutical grade copper peptides like GHKCU, one of the most research regenerative signaling molecules that we can get access to. That actually naturally exists in your body. Now Vitali evolved that science by introducing exosomes, the body's native messengers. They use zero age exosomes, which means the signals driving repair are cleaner and more efficient. Paired with copper peptides, it's less about forcing change and more about supporting skin to do what it already knows how to do. If you think about longevity in terms of mitochondria, signaling and long-term resilience, Vitali's skincare built for your biology. All you have to do to get your hands on some is visit VitaliSkinCare.com and use code NAC20 for 20% off. It makes so much sense, right? You're going at the stem cells in the bone marrow. The stem cells in the bone marrow are the found, I mean if there is a fountain of youth in the body, if there's a fountain of regeneration and repair, it's those stem cells and they will, and I think you said this earlier, they will differentiate into many different cells that are applicable to many different systems. So it's the elegance of this is getting it at such a foundational level that then the body just decides what the next priority is on the list. Exactly. That's what it is. That's wild. And so I just want to go back to that childhood disease just because it's my own curiosity. Would that also, would that disease not also be a really good candidate for some kind of gene therapy someday to fix that deletion in the DNA? Many, many tried of course. So the complexity of that. So we know how to fix genes in the nucleus in the mitochondria, it is way more complex because the DNA is right within the two membranes of the mitochondria to deliver components for fixing the DNA to pass through these two membranes. And then you not only have one or two copies of DNA, you have multiple copies of mitochondria. So to fix that is more of an issue. And you're just keeping them alive until somebody figures that problem. Maybe yes. And maybe even when they will need more mitochondria, we will supply them with. There's another accelerated aging disease where it's not the same one. Progeria. Is there an application for progeria with mitochondria? A specific gene that is mutated and causing the disease. And I think a gene therapy in that case will probably be applicable. So within the context of this discussion here, is there something to be said about mitochondrial resilience in all this? I think we have a way to control our mitochondrial resilience. I wouldn't wait until we age and develop chronic diseases. I think we can definitely behave while we are young and maintain our mitochondrial function. I think getting that into our awareness actually starts resonating very early in our lives and it will impact everything we do. It's the clarity, brain, how we think, it's the sleep quality. It's our metabolism and our ability to absorb food and how do we behave when there is an infection? When our body needs to activate our immune system. So we cannot predict when there will be a wall of pandemic or when our immune system will be challenged. We need to be prepared to that. And being prepared to that meaning our mitochondria needs to be resilient to all these lean cells. And I think many of the surroundings, the air pollution and the water that we drink and the food that we eat, the medications that we take, they have a very strong effect on the mitochondria and not positive one. So we wear to that all the time and making sure that we consume only things that benefit our mitochondria is something that we need to take in mind if we want to age healthier. Yeah, I love that. I have a question. This is a little bit at a left field. Do you have an opinion on non-native EMFs? On what? Sorry? Non-native EMF, electro-magnetic frequency. Like a lot of people talk about the impact of 5G on the cell or and you know, basically this new input that our bodies have not had to evolve. You know, the earth has electro-magnetic frequency, like natural of course. But you know, you may not have thought about this, this hasn't, maybe this hasn't come across your desk yet or you're not here. You're so busy. So okay, so we can talk about that the next podcast because there will be another one. All right, let's talk about aging a little bit. So when at one point in life, do you think we start to feel or experience that decline? Is there, I've always heard at the age of 30 is when things start to, you know, like up until 30, our ability to regenerate and repair is really good and it, and you know, 30 is an arbitrary number. It could be 32, 31. Like, is it that 30-year-old where we start to really kind of experience that decline and is that backed up by mitochondrial science, do you think, or is it later earlier? What are your thoughts? So we're currently measuring those mitochondrial functions in different ages and I'm sure that in two years, I will have a precise answer for that. Okay, but actually people say that starting 20, we start to age in decline. It's very depressing. I know, I'm sorry. Oh my god. Yeah, but I think it's very different and very personalized between people and definitely different between males and females as we know, we age very differently. So I think when we will do our analysis using our mitochondrial biomarker to determine the health of mitochondrial and different ages, we will take into consideration also the different sexes and then try to build those mitochondrial scoyne systems. Yeah, health and disease and then then they'll have a better answer. Yeah, there's recently, there's recently been some noise about these two inflection points, particularly in women where aging accelerates. And I think one of them was at 40, which makes sense because that's where menopause, you know, give or take a couple years, that's when it starts to kick in. And then 60. Yeah, do you think, I mean, again, I'm asking for opinion, I think this is an area that you're going to actively be studying. But how much do you think this mitochondrial kind of drop in function might be playing exactly into those and why, I mean, you know, is our, is the loss of hormones affecting mitochondrial health? Absolutely, 100%. And actually, the decline, the mitochondria could be the clock that caused the decline in hormone production and that's where you see. So it's what starts, right? And I believe in the mitochondria, that's all kind of the trigger for that because I told you about the involvement of mitochondria in steroid hormone production. Let's draw the particular alone. Yeah, I will never forget that. It's 60. It's already a multi-fectorial event. It's already when the mitochondrial dysfunction starts circling back on different pathways. You will see telomer, shortening, you will see reactive oxygen species, you will see so many dysfunction of the immune system, exhaustion of the stem cells. All of that is happening already at 60. So it's already too late. This is why I mean that you need to intervene very early to prevent dysfunction of mitochondria, which is one of the earliest things that you see in the right process. So I was going to ask about stem cell exhaustion. Talk to me about stem cell exhaustion. Is it a thing? What is it? And do you think it's coming from the mitochondria? I mean, I'm listening to you now. I'm like, everything's coming from the mitochondria. Of course. Talk to me about stem cell exhaustion because it's a term that I think gets thrown around a lot. And I don't know that people fully understand what it really is and what it isn't. And then let's tie it back to our mitochondria. Yeah, it's eventually you measure the outcome. So for example, we know that the ratio between lymphocytes and other cell types within our blood system is changing with age. Why is that? You see just the outcome eventually. You see a very poor responding immune system, but it starts with your stem cells. This is how we know that. So exhaustion of stem cells means cells are actually lacking the energy to start differentiating. Okay? Yeah. Because that's what you need as a trigger to start producing new blood cells. New blood cells meaning new immune cells and different subtypes of immune cells. So as I look at stem cell exhaustion is their ability to renew themselves. A stem cell has to be able to renew itself. And all the time to start with this new daughter cells that are differentiating. So the different affects two pieces. They're in new ability and the differentiation capability. And the lack of energy is something that just puts cells into senescence. Just like you said, if I don't have energy, now my what I will do is just hibernate, right? I don't waste energy. I'm sleeping now. Don't bother me and not bothering me. Meaning I'm not doing my job. I'm not replicating. I'm not differentiating. I'm not producing the cells as I should produce. Stem cells also of course have a role in regenerative capacity. So when they migrate into a tissue, they will need to renew that tissue. Every renewal process requires energy. The production of proteins within a cell that is one of the most important piece of the cell needs to do. Either secreting factors or producing enzymes for the cell to function, it only requires energy at mitochondrial function. I think eventually this is what exhaustion is all about. Renewability, differentiation, and regeneration. Yeah, no, it's foundation. It's foundational. Like the immunosenscence has got to be fundamentally. You've described it three times now. It's a mitochondria. It's a lack of energy. Just to go back to the zombie slash senescent cell, I've heard them described as grumpy old men. They don't even just sit there and hibernate. They secrete cytokines and inflammatory molecules. In the absence of a neighbor that will create one of those nanopores and donate mitochondria so that they can live to fight another day, then they are like, okay, fine then. I'm just going to take everybody down with me. Exactly. Kind of attitude, which is interesting. Okay, you've referred to neurodegenerative diseases a couple of times. How foundational do you think mitochondria role? Is it a foundational role? Okay, because we talk about accumulation of plaque. We talk about the death of neurons, which I'm sure you're going to sit there and explain to us in a very clear time. Is everything to do with not enough mitochondria? But in treating these diseases, should my mitochondrial treatment fundamentally be one of the pillars, because it's as you said a few times, but a lot of these chronic diseases, it's not just one thing, right? It's never going to be just one thing. But should addressing mitochondrial function foundationally be one of the pillars of dealing with these things, whether it's slowing them down, reversing them or avoiding them in the first place? Yeah, what you need to do with brain cells is really preventive death. What happens in neurodegeneration is either the cells stop functioning and they remain stuck in the tissue. Like we said, oh, they are dying and again, remains stuck in the tissue and they are inducing further damage. When we talk about inducing mitochondrial function is actually preventing the death of neurons and prolonging their life and activity within the tissue, because neurons are not regenerating. We avoid the amounts that will keep us alive all our life and the amount of energy that the brain demands is huge, it's enormous. So where does it get this energy mostly from the mitochondria? It's more than 80 percent coming from mitochondrial function. So of course, neurodegeneration, especially in aged individuals, is due to mitochondrial dysfunction. We see that greatly. As we age more, more components join the party and of course, it's accelerating everything, but the earliest times is really mitochondrial dysfunction. The problem is how do you solve mitochondria dysfunction in the brain? That's really problematic. You have to only handle what's in there. You cannot deliver anything new. It's very, very difficult. Even drugs are difficult to brought into the brain. It's a huge challenge. When we have treated our patients, they also suffer from neurodegeneration. I mentioned Pearson syndrome. There are also other more neurological diseases like Karen siren syndrome and Liz syndrome, all our primary genetic mitochondrial diseases. We observed an improvement in neurocognitive function. We don't really know how to explain it. I have to tell you. Because if you remember, we treat the stem cells in the blood. How does it influence the brain? But we have seen it because it's like, again, the immune system and the signaling. What you're doing is getting in at such a foundational level that allows the body to do what it does. So you don't have to get to the brain. The body is like, we can get there. All you got to do is give us what we need. It's so incredible. I'm going to use the word elegant again because it is such a and I mean, nothing about this is simple, but it is truly so simple that if you can get to that first piece where the body is producing what it needs, then it can do what it needs to do. Like that is just wild to me. But we are scientists. I mean, and we have this curiosity to understand how things are working. And of course drug development. If you want to succeed, you need to understand how to work. This is what initially we only focused on the bone marrow and the blood system to show improvement. But eventually the impact that we see in the patients, that's our trigger to go way far and beyond. Just as rare diseases and the genetic disorders really try. We feel very brave now. First of all, our therapy is safe. So it's not, do know how the first of all, and then the multi-organ improvement, we had a patient with severe epilepsy and stroke-like episodes on a monthly basis. But for six years, we prevented those after a single treatment, because it was like unbelievable. So we really try to understand how to deliver this therapy way broader. The brain is very interesting, but very challenging. We will just have to face the clinical outcomes. See them? And eventually that would be the proof. I don't think we'll ever understand everything about how it's exactly working. But I think that's the most important thing. Because if you save the life of a child with a piercing syndrome, but you didn't fix these brain. So yeah, you didn't achieve the ultimate goal. So we can say that metabolic disease, like diabetes, non-alcoholic fatty liver disease, cardiovascular diseases, are going to have that very minimum have a mitochondrial component. Not intentionally linked to mitochondrial, under-mits malfunction or under-performance. Do you think are we misclassifying diseases that are actually mitochondrial and origin? I mean, fundamentally the question is, do you think there's a disease that isn't founded in my God, you'll dysfunction? I would do it in the brain. You can try and search in any search engine, any disease with mitochondria, you will find a connection. I tried this before. You can go ahead and do that. But definitely, I mean, whether it's stouted a disease, or it's an outcome, this is a question, but I can tell you, for certain, any disease will benefit from improvement of mitochondrial function. Because fundamentally, if you get more energy, you can fix anything with the same. Talk about, you spoke about diabetes. Insulin production is an energy process. It has to be coming with improved mitochondrial function and then you'll get more insulin production. Control, you know, insulin production, control, you know, glucose metabolism, all of that is energy dependent. And mitochondrial dysfunction will actually induce further damage into the cells. If you improve that, you have a better chances to fix even the initial problem that the cell has. Yeah, 100%. Cell accumulates mutations, for example. And now you improve mitochondrial function. You have better chances to initiate DNA damage response, all to improve the function of those machineries that will fix the cell. And if it's not, mitochondria will induce the apoptosis, the cell suicide, to eliminate the bad cells, which is also fundamental. So yeah, I think there is even, I tried it, even one disease that doesn't have mitochondrial function eventually. And those diseases will probably benefit for mitochondrial function, yes. Yeah, I would think so. Even like anything in the eyes, like as we see the decline in the eyes, like the eyes are so dense and mitochondria. Before our call, I had a full discussion about the different diseases that could benefit for mitochondrial transplantations. You named it. All right, let's move into mitochondrial biomarkers, you know, measuring the invisible. So this is what your work really becomes also about. Like, there's obviously the mitochondrial transplantation. But as you said, in order to quantify what you're doing and to understand the needs and the outcomes, it's really about measuring something that nobody really has been able to directly measure so far. And that's a big aspect of your work. So clearly, I mean, you know, we don't measure them because we can't, we don't know how, or we haven't developed those strategies. So what are the most promising biomarkers in mitochondrial biomarkers you're seeing coming out today? First of all, you cannot treat, but you cannot measure. Okay, this is fundamental knowing that drove us to develop those biomarkers. We wanted to develop a therapy, but we realized there is no way to measure our success in this therapy development. So let's develop biomarkers. But then when we were exposed more and more into this world of mitochondrial diseases, we realized that it is way beyond just the primary genetic. And there is a whole world of secondary mitochondrial diseases and a whole world of age-related mitochondrial diseases. And you see people that look completely perfect. I mean, they go to the doctor, they say, I feel very frail, I feel very tired. I don't have the power, the end of the day to climb my stairs to go home. And they say, your blood tests are perfect. Nothing shows that you have any disease. Exactly. So we are not measuring, obviously, what drives our mitochondrial dysfunction. So the most important things, mitochondrial dysfunction is it's it's it's tricky, right? Because I just told you they have so many functions, functions of which ones are the ones we should pay attention to. So then no of mitochondria are critical. Even if you have some of the mitochondria dysfunctional, but you can increase the content, you can eventually increase the content of the good mitochondria, get enough mitochondria to get enough energy. Okay. So the number of mitochondria are really critical. The function that we are looking at is of course the ATP production, but ATP could come from glycolysis too, right? Not less mitochondria. So we are coupling the ATP production to the respiratory chain activity of the mitochondria. We are doing home because eventually you know, you need to know what is the specific ATP produced by the mitochondria per single mitochondria within the cells. So we're doing all three of them together. And those are the three biomarkers that we're using to calculate the mitochondrial scrolling of a healthy individual versus a child or an adult with the mitochondria, primary mitochondrial disease. And now every person that will come and be tested with this biomarker, as we can say, your skull is somewhere here. Your health healthy age-match control is here. So you're doing great. All your age-match control is here. You're here. Primary genetic mitochondria disease is out here. You can go further down or you can get a therapy and move up the scale into your age-match control. You can also go on a tail into a younger phenotype, which would be fantastic. But that allows us to really measure the quality content and function of the mitochondria in different people. We are also looking, of course, at the mitochondrial DNA because we want to know the mutation load in the mitochondria genome, which is fundamental to all this non-functioning mitochondria. And there is also another biomarker that is released from this cell organs that is called GDF-15. GDF-15 and mitochondrial dysfunction goes hand-in-hand. So, overall five biomarkers that are currently used in our clinical studies to first call different people different ages with their mitochondrial scoyne and then test how our therapy improves the function or the levels of those biomarkers in the blood of these patients. Fundament. It's like a biological age test for your mitochondria. Exactly. It's a biological aging test for your mitochondria. Exactly. Which is going to drive your biological age. Exactly. This project, I have to say, was funded by the foundation called Countdown for a Q. I've just returned from Atlanta for an annual event of the Countdown for a Q, where the people who drive this foundation are people who look completely normal. When you speak to them, they are telling you all the symptoms that they are suffering as to a secondary mitochondrial disease, young, beautiful, healthy people. They look very healthy. Eventually, when you test them, all the blood is fine. There is nothing, but they cannot climb the stairs in their house. They come to a situation where they can't even feed themselves and they need help. It's mind blowing how needed those biomarkers are. This foundation has identified our project as one of the funding and they gave us the grant to develop those biomarkers way far and beyond than what we initially intended to do. I told you, in two years, we will meet and I will tell you exactly what should be the scope of the mitochondria at each one of the ages. Then we can start screening for a few days. Wow. Wow. Wow. Okay. We talked a bit about the transplantation that you're essentially in a very simplistic way, trying to induce endosymbiosis outside. You're using donor mitochondria from cord blood. I'm plus-centa-sorry. Essentially, unless we get into a world where we all bank our moms mitochondria when we're born so that we can use it. You know what I mean? Like, later on in life, I can see on a prenatal level, at some level, that mitochondrial support for the mother would be wildly important. I mean, it's wildly important through your entire life. Is there anything in the transplantation trials originally that surprised you? I think the brain, the impacts on the brain was something really surprising to us and the kidneys as well. I mean, the improvement, because usually they say that once kidneys phase, you cannot reverse kidney insufficiency because of the fibroresist that happened. So I think that was really, really surprising. But overall, knowing how important mitochondria, oh, I wasn't that surprised if I really wanted to put it in place. No. Yeah. Amazing mitochondria. And I also knew that the placenta are very unique in their nature because they just fed a baby for nine months and now we are using it. We are behaving like it's trash. And all of a sudden, taking that very, very healthy young organ, producing the mitochondria, it was mind-blowing. It is way more active than blood mitochondria, for example. So if you compare mitochondria from placenta to blood mitochondria, you will see that there are 10 times more active than the blood mitochondria and they contain more mitochondrial DNA than blood mitochondria. So overall, it's like a super organ for mitochondria. And that I knew for my PhD already, that's, let's say, the mitochondria very unique. And we found something to do with this trash. So they're very happy about it. Are there any safety concerns that have to be solved, do you think? Like, could it, I mean, I guess in this case of an existing cancer, you've already said that the cancer is already hijacking sometimes. Healthy cells might have control stores. Are there any other safety concerns that have come up for you that you've seen so far that you think, well, you know, we might really need to. Definitely. I mean, there are always safety concerns around the new therapy and intervention with some evolutionary conserved processes that that was always frightening. This is why we started, by the way, first of the maternal mitochondria into the children because we didn't want to go first into an alogenetic donor. But today, the main safety concern, where can we really mix different mitochondria in individuals? Can I take or borrow mitochondria from one donor and use that? Will I have any immune responses? Will we get rejection? And eventually, we didn't see any immune response again, the mitochondria. There are no antimitochondral antibodies that are produced due to this process. So overall, in 27 patients so far, it seems to be safe and tolerated. So those risky aspects where I've been overruled, the cancer, I think, is always an issue. I mean, will we induce cancer because of this mitochondrial orientation? But actually, you know, we've done, we went to one of the world's experts. We focused, if you recall, we are focused on one old age-related disease called Miele dysplastic syndrome. And MDS has the risk to develop into leukemia to AML. So went to one of the world's experts before we started those in patients with MDS. And he has a mouse model. This is a lab in Memorial, Stronkaterin, in New York, led by Dr. Omar Abdul-Wab. So he has a mouse model that is accelerated age. He has MDS and develops AML and all the mice die from AML. So when we took the stem cells of that mouse and we transplanted them in a healthy mouse, all of the mice died within four weeks. If we augmented those stem cells with mitochondria and that was supposed to be only for safety, the question was whether we induced faster the leukemia. Did they die in a week? The cancer was they actually have an extended lifespan and it did make some low-chemical progression. So that was comforting. I said, okay, we are safe to go into humans now because not only we are not accelerating low-chemical conversion, we are actually protecting them and we are delaying the leukemia. Well, based on the conversation we had, you're re-engaging the immune system to do what it does. Which will, I mean, it sounds to me, I mean, again, oversimplification, through the overview. But, you know, it, it, it, based on this entire conversation that makes complete sense. Okay, we're down to a last couple of questions. Stay with me. I could keep you here all day. I would imagine that down the road when this has been refined and tested and this is going to become at least as calm in a stem cell therapy, but I would imagine that this would augment stem cell therapy. Like, that this would, this would underpin, like, because you know, we're seeing so many amazing things coming out of stem cells, exosomes. But now, if we're bringing the work crew, the stem cells with the exosomes, the, the, the, the instructions, but now we're also providing extra energy to the cell to actually do the work. You can imagine that this would explode in terms of efficacy, or am I missing something? I love it. Yes, exactly. We all think about how to combine therapeutic approaches in order to reach the maximum capabilities of a human body. And this is exactly it. So if you, how stem cells form an elderly individual and you infuse them back, they actually all, they might occur, all it won't be enough. Taking those stem cells and now augmenting them with young and healthy mitochondria will boost their activity. That's exactly what happens also when you grow cells in culture in order to produce exosomes. Growing cells endlessly in culture caused the cells to age. They're mitochondrial aging. Now if you want to produce healthy functional exosomes, boost the cells with mitochondrial, get more exosomes and healthier exosomes. So for the, it's everything, you know, people are trying to reprogram cells to come back to their young nature, like IPSC's, blue-putten stem cells, to go back and be embryonic like, right? Those are the newest things with gene therapy, trying to overexpress the amannacophactors to make cells young and healthy again. But how do you fix their mitochondria? You cannot do that. You have amannacophactors. So let's augment them with mitochondria and then you see how this combination therapies will solve multiple problems at the same time and it's not one plus one, it's exponential because of the impact of mitochondria. Do you have any thoughts on NAD, NAD precursors supplements in terms of their import, something that people can do to support mitochondrial function at a foundational level? Yes. And is there any other support that stands out to you? Yeah. So NAD, of course, is one of the important substrates, the cells mitochondrial function, super important, yes. And actually available and consumable by the cells, so it's something that's relatively well-studded and it seems like to produce a good results. In addition to NAD, you can see coins and Q10, very important, you between all and not you between all. So a structure that can be consumed by the cells and be actually available for the mitochondria. Coins and Q10 is one of the most important co-factors for mitochondrial energy production. And important to know, it is blocked when we are taking statins. So anyone who's taking statins to reduce the cholesterol is actually blocking the synthesis of coins and Q10 within our cells and this is why supplementing with coins. In that case, is a good thing. And one of the things that I've spoke about, you know, raising your free fatty acids, acid that induces your mitochondrial activity and mitochondrial biogenesis, this is important, easily controlled by the food that we eat. Sing, consume oxygen, do yoga because it's so good, yes, for mitochondrial activity. And one thing I tried on cells on culture and is working, a component called resvertoid. It is found in grapes, red grapes only and actually walks. So, again, the source is important, the no one is actually. But resveratone is something that induces mitochondrial biogenesis. So the increase of mitochondrial content within the cells, I know I tried, it's working. Are there any lifestyle or other interventions that actually you believe really do move the needle on mitochondrial biogenesis? I think free fatty acids is going to be one of them just because of the energy. Is there anything else? So I'm going to throw a couple of things at you and you can give an opinion if you have it. There's red and neon for red light, infrared sonas, hyperbaric therapy, fasting, hyperbolic thermophypobolic chambers, yes, induce mitochondrial function. By the way, increase also stem cell content within the blood. Great signs behind it, totally agree. I don't know about red light therapy, I'm not sure if anything else. I'm all about the signs of eventually. And the last one, what did you mention? The infrared sona or fasting. So, interwins are also the devices that you use, right? So, absolutely. Just this mitochondrial function, yes. Again, exercise. Absolutely. Okay, when you build muscle, what you are actually doing is increasing the mass of mitochondria within your fibers, okay? Massive fibers, that's all what it is. This is how you look at the unit 14 in order to expand mitochondria within the muscle fibers. And what you see is more energy, the more mitochondria in the muscle, more energy, and then more tolerance and exercise tolerance. Excellent. Also, when you exercise, of course, you consume more oxygen, you feel better, energize, it's all over. It's everything. It's great. Okay, last two. What is one mitochondrial myth you wish would just disappear? Oh, that's a good, well, you know, people think that mitochondria are single. Actually, mitochondria are plural. So, it's a mitochondria for one mitochondria or plenty. And what people, every time they are surprised, oh, we don't only have one mitochondria within ourselves, no, we have tons of them. So, this audience, you know. Yeah. Okay, last one. And this is something you mentioned at the beginning of the podcast that I think is so important. You talked about emotion, you talked about joy, you talked about impact of our, of something that is really not tangible, but that impact on mitochondria. Do you want to speak to that a little bit? Because I think that it's, I want the audience to walk away with something that they can start tomorrow, right? Or do I? And just, I'm a scientist who's been so deep in this for so long, I'd love for you just to give, to share with the audience your thoughts on our emotional spiritual inputs that can they affect our mitochondria? Yeah. I think when we we all, when we feel good, I mean, we feel energized, we feel so powerful. And I think when I go to visit my parents and my father is now 84 years old, and unfortunately suffers from a third-age epilepsy and consumes drugs that I don't have, he's my daughter further. When I come to him, what I tell him, that is sing, sing, when you sing it, it's like you float your body with all your energy and you feel so good. And now my mind thinks why is that? And how come one of the most surprising things I've ever met in a scientific conference was a group coming from, from Canada, from from from Toronto, therefore, a psychiatric, yeah, psychiatric hospital. And they presented data that I was just shocked and overwhelmed, schizophrenia, mania, depression, all this, your bad diseases of the soul are eventually bound to mitochondrial dysfunction. I was shocked. I never knew that even. So our mental health really depends on the quality and health of all mitochondria. That was shocking to me and eventually exactly everything is eventually bound together. Why should we live those long life unless we feel good, we feel healthy, we feel energized and we're good health, mental health as well. So they presented data showing the 30% of bipolar disease patients carrying mutations in the mitochondrial genome. It's like it's crazy. I think there are so much to it of how we we we capture our life, our health and how much of it is in our control in mitochondria. This is the case, we can really control it by simple. Yeah, and that was I think that's what I was getting at. Like in a person who is not chronically ill or has a serious condition, is it possible that bringing bringing attention to living and joy and gratitude and in a positive mind can also have a very powerful impact on how we age and how our mitochondria behave or thrive. Is there anything people can do when they're in a position that they are ill and they have to take medications that are in a negative to the mitochondria but saving the system. So you know what I mean? Like sometimes we're in a situation where we need a medication to get us through a crisis. Have you seen or are there things that people can do when they're taking medications that are fundamentally toxic to the mitochondria? Like a statin for example, you mentioned co-Q10. Are there any other interventions you can you can share with the audience that they might want to consider and talk to their physicians about that could be helpful to supporting the mitochondria which ultimately could support their recovery in some small. So you know for our mitochondria disease patients there is a list of drugs that are forbidden for mitochondria disease patients because they are harmful for the mitochondria and they can further deteriorate. Of course in some conditions it is not possible but there are drugs that are more toxic to mitochondria than others. For example I mentioned epilepsy that my father suffers when he when he started on Valproic Acid which is the first line of drugs that epilepsy gives. He started deteriorating like crazy and then when I was reading about it I actually it is known that those drugs have mitochondrial toxicity. So if for a certain physiological condition there are multiple approved drugs I would look into the literature and see which one of them has less mitochondrial toxicity. Of course we can supplement just like you know people who are taking antibiotics are also taking probiotics in order to prevent the death of our gut microbiome. We can supplement our mitochondria as mentioned with the supplement that you just we discussed a minute ago in order to improve the mitochondrial function and to rescue that. So there are certain antibiotics that are also harmful to the mitochondria. I would try to avoid those again it is available. It's a data that is available throughout the networks you can easily know which antibiotics have more mitochondrial toxicity versus others. So just being in attention into mitochondrial health will eventually allow us to ask the right questions either our physician or sometimes it's just the information that is available throughout the network and you can really find out so much more about your health. My goal is that any drug that is being developed in the first stage of development the drug will be tested for mitochondrial toxicity. I was shocked to know that most of the drugs about not most but about 50% of the drugs that we use today have known mitochondrial toxicities. This is crazy. You can prevent that. You can screen in advance for drugs that are safe for the mitochondria will prevent the outcomes of using those therapies. So this is my message. It's so self-defeating right? Like you're keeping in person alive and denying their body the ability to do any kind of repair work. It's wild. All right. Listen we need our you know this is like when you're the longest goodbye. I have to let you go so that you can go answer all of these incredible questions and bring your incredible work to market which I think is going to be so unbelievable for the whole everybody. Everybody. So Natalie please share with us any information that you know anything that where people can learn more where they can follow your work. If there's anything anybody can do to help I think just please share with us any anything that people or just even follow the work. Yeah of course so we have our website of course minovia tx.com we have our LinkedIn and Instagram and we are also on Twitter so I think you know just follow our activity. We are trying to be as helpful as possible for the entire community and to implement the importance of mitochondrial health as you've just heard. It's not just about getting a therapy or a drug approved. It's been mindful to our mitochondria very early on in our life as soon as possible and just bring it forward because eventually what we learn and experience on our bodies could be beneficial to others. So share that information follow what we do and give us feedback and send questions. There is an info at minovia tx.com feel free to write to us and ask and questions we find the time to answer everyone so do that. That's amazing thank you so much this has been I can really appreciate you know I'm always I'm always interested in my topics but this one got me so we will remain Natalie maybe in a year or two when you've had your next couple of breakthroughs and I think people will be waiting for that episode I know I am thank you so much. Thank you it was a pleasure. Hey folks just a quick reminder that all of the information presented in this podcast is for information purposes only no medical advice no diagnosing no treatment suggested here before you try anything that you hear about or learn about here make sure that you check with your medical provider.