Elena Buglo, PhD: Exploring Genetic Diversity, Neurodiversity, and the Power of Unique Physiology

In this captivating episode, I'm joined by Elena Buglo. Elena's background is a PhD in neurogenetics from the University of Miami Miller School of Medicine. She now works supporting a rare disease biotech company in medical affairs, and she leads with great passion for neuroscience, genetics and genetic editing technologies. In her research work she utilized CRISPR technology to model and study various rare disease genes. She recently started her podcast on gene therapies and precision medicines. Check it out and support her by subscribing and giving a 5-star review at : https://podcasters.spotify.com/pod/show/gene-therapy-insights

Elena discusses the significance of genetic diversity, advocating for a personalized approach to health that celebrates our unique genetic makeup. She explores neurodiversity, challenging conventional views on cognitive and physiological differences, and emphasizes the holistic interconnectedness of our biological systems. Her expertise illuminates the critical role of mitochondria and other cellular components in overall health, highlighting the need for comprehensive health strategies.

This episode is a must-listen for those interested in genetic science, personalized medicine, and the future of healthcare. Elena's perspectives encourage a deeper understanding of our biological uniqueness and the potential of gene editing technologies to revolutionize health and wellness. Whether you're in the medical field, facing genetic health challenges, or simply fascinated by science, Elena's insights offer valuable guidance on navigating the complexities of human biology and the promise of tailored healthcare solutions.

Key Points From This Episode:

Sleep and Overall Health [00:01:53]
Introduction to Neurogenetics Discussion [00:03:53]
Explaining Neurogenetics in Simple Terms [00:05:0]
The Impact of Debilitating Genetic Diseases [00:07:13]
Genetics vs. Epigenetics [00:09:01]
Personal Genetic Insights and Lifestyle Adjustments [00:14:05]
The Complexity of Genetic Influence on Health [00:27:10]
The Risks of Over-Optimizing Health [00:29:57]
The Role of Geneticists in Healthcare [00:37:45]
Genetic Testing and Personalized Medicine [00:42:50]
BDNF Levels and Genetic Variability [00:44:46]
Genetic Compensation and Physiological Adaptation [00:47:59]
Analogy for Genetic Function and Adaptation [00:53:52]
The benefits of gene editing [00:56:35]
Neurodiversity and unique phenotypes. [01:03:17]
Living with ADD and medication [01:05:39]
Genetic dating app. [01:11:40]
 Reproduction and genetic optimization. [01:13:23]
Attraction to different genetic backgrounds. [01:18:23]
Genetic attraction and relationships. [01:22:37]
Lysosomal storage disorders. [01:29:57]
Unique backgrounds and accepting differences. [01:33:17]
Genetics and intuition. [01:39:05]

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People

• Elena Buglo
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• George Church:
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Chapters

• 0:00 Trailer
• 0:26 Magnesium Supplement
• 4:14 CRISPR gene editing
• 10:59 Epigenome editing
• 13:11 Genetic plasticity and adaptation
• 18:05 DNA and debilitating diseases
• 23:00 Partially expressed genetic disorders
• 28:16 Glucose deprivation and stress
• 33:10 Less is more
• 38:27 Genetic origins of cerebral palsy
• 43:19 Genetic test and BDNF levels
• 46:10 Genetic diseases and natural history
• 49:37 Gene expression and BDNF factor
• 54:01 Water pressure analogy
• 56:35 The benefits of gene editing
• 1:03:17 eurodiversity and unique phenotypes
• 1:05:39 Living with ADD and medication
• 1:11:40 Genetic dating app
• 1:13:23 Reproduction and genetic optimization
• 1:18:23 Attraction to different genetic backgrounds
• 1:22:37 Genetic attraction and relationships
• 1:29:57 Lysosomal storage disorders
• 1:33:17 Unique backgrounds and accepting differences
• 1:39:05 Genetics and intuition

Transcript

Elena Buglo: We are all unique and if you just, you know, using all kinds of biohacks, almost like mindlessly, you might find a spot where it's going to be too drastic for you. Like don't, you know, when you push too far. So it's all about balance and kind of like knowing and learning yourself, learning truly the science behind you.
Andres Preschel: There is only one supplement that I think almost everyone on this planet should be taking and that's a full-spectrum and highly bioavailable magnesium supplement because, well, let's face it, ever since the industrial revolution, our soil has been depleted. of magnesium and therefore our food is depleted of magnesium and on top of that our modern environments which are inherently overstimulating and stressful are constantly depleting our body of magnesium and unlike other nutrients this is not something your body can produce on its own it literally needs to get it from the diet. And one individual kind of magnesium alone is not enough. You actually need seven different kinds to support over 300 biochemical reactions that help regulate your nervous system, red blood cell production, energy production, managing stress and emotions, etc. And so the folks at Bioptimizers have made it very easy and convenient to add back in what the modern world leaves out. They've created Magnesium Breakthrough. Now I've been taking this for the past two years and the biggest benefits that I've seen are related to my evening wind down sessions and my sleep. I tend to be pretty overactive in the evenings, just totally overthinking everything that I do. And this has helped me wind down and get more restorative, more efficient to sleep. So I wake up feeling way more refreshed, more energized, more clear, more ready for the day. And the way that I see it, sleep is upstream of essentially every other health and wellness related habit and decision. Because if you're sleeping better, automatically you're going to have more regular cravings, you're going to have higher insulin sensitivity, you can derive more of all these inputs like fitness, right? You make more gains, you gain more muscle, you burn more calories, and you wake up feeling refreshed so that you can do it again and again and again, and then beyond the fitness you have more energy to go for a walk, to do fun activities with friends, you are less stressed so you can socialize anxiety-free, and you're also going to be retaining, refreshing, and refining your skills and information much, much better so you won't forget any names. And, yeah, I mean, like I said, over 300 chemical processes that you're supporting with magnesium. And sleep, I mean, wow, better sleep is just a better life in general. So, I found that extremely helpful on a personal level, and I'm sure that you guys will find it helpful too. Your mind and body, and maybe even your spirit will thank you. So anyway, if you want to get a sweet little discount off of this amazing, amazing magnesium supplement from Bioptimizers, all you have to do is visit the show notes. So you scroll down right now, takes just a couple seconds and boom, you'll have access to all seven different kinds of magnesium that your body needs. All you have to do is hit the link and use code KYP from Know Your Physio. KYP. That's all. Enjoy 10 to 22% off depending on the package you choose, whether or not you subscribe. I'm obviously subscribed because I don't even want to think about whether or not I'm going to get this essential supplement in the mail. And yeah, hope you guys enjoy that awesome stuff. And that's all for now. I'll see you guys on the show. Okay, here we are on the Neophysia podcast with my lovely neighbor and good friend Elena. And today we're gonna dive into a number of topics that I certainly have not covered on this show and that I haven't heard covered on really any other because they are very niche topics that a very small subset of scientists have access to. awareness of but They are topics that have the capacity to change Pretty much everything about our lives as we know it a few years from now so we're gonna talk a little about CRISPR genes, maybe some gene editing and Maybe some more stuff some more fun stuff That being said Elena welcome to the show. I'm excited to dig into all this with you

Elena Buglo: Thank you for having me. I'm excited to share more about kind of like what I do and all the exciting things that I've been working on.

Andres Preschel: Yeah, for sure. So so typically I start the podcast asking people why they do what they do. But before I ask you that question, before we get there, I don't know if you've ever been in an Uber where you just make small talk and you kind of tell people like an Uber driver, like what you do, or maybe you're in the elevator and or a coffee shop. People just say, hey, what are you working on? What do you do? How would you describe what you do to the average person?

Elena Buglo: Um, I usually say that, you know, I work in genetics, specifically in the field of neurogenetics. And, um, so basically I work with, by helping to understand, they're difficult to understand diseases, rare diseases. Um, you probably could have heard of them. Maybe, you know, somebody who has such a debilitating disease, but usually you don't really see these people on the streets. These people have, you know, very horrific lifestyles and they have very poor quality of life when there is truly a debilitating genetic disease that manifests either early or later in life. But I think all of us heard stories of people like famous athletes or even physicists, for example, who have ALS. So the degeneration that has some genetic component, maybe some non-genetic component, and kind of like people losing their livelihood ability to maintain their daily abilities, daily quality of life, daily tasks, daily activities. And from the standpoint of more earlier onset diseases, those that manifest purely genetically very early on, Those are the kind of diseases that, again, you wouldn't see these people on the streets. Usually they're wheelchair-bound. There is 24-7 care of their caregivers, families, and multidisciplinary teams of doctors. And often we don't truly know the stories unless we're in it, unless we truly know somebody who has such a, you know, such life. And what I do is I help to understand such diseases. I'll help to, right now, basically in my earlier past, I've done research on actually understanding which genes contribute to manifesting as a disease. And later in life, right now I'm working on the side of industry in medical affairs where I help different healthcare providers to also better identify these patients who they don't normally see. And just like regular normal people, if they don't see these patients too often, they don't recognize them very well. It's really hard to keep up with genetics and all of the genetic discoveries and what they truly mean. to properly diagnose and also very hard to keep up with the treatments that are coming up with these rare diseases, which are called now the era of precision medicines. So what I do is relay this information, help them understand how to identify people who might be having genetic disease and also helping these patients to find the therapies that might be in development for them.

Andres Preschel: Lovely, and that's a very concise way to describe it. I know that the intricacies of this can be so vast and just so overwhelming for non-scientists, even myself. I mean, technically I'm a scientist, right? But I don't even want to get into the trenches with you about specific genes and what those might Tell us what they might reveal So I want to make this as practical as possible for people that have that I've never seen this before and I really want to shed light on the power of this technology for most people Before we dive into some of these intricacies before you illuminate this for me and for the listeners Can you tell us difference between genetics and epigenetics I've heard of the analogy of you know, genetics load the gun lifestyle pulls a trigger, but what do you have to say?

Elena Buglo: So, you know, fair question. What I have to say is, first of all, I'm not an epigeneticist. Basically, there are people who, you know, dig into epigenetics. They know so much more than I do. Basically, genetics is, once again, the information that is written in the DNA. There are some coding and non-coding parts of the DNA. Basically, some of the parts of the DNA become proteins that do work in the body. And other parts, so all kinds of things that we used to believe are junk or apparently there's also like 40% of human DNA has transposable elements and like ancient retroviral genes that came from ancient viruses. So we didn't know what all of those things are doing and what those there along reads of DNA are doing is often regulatory functions. And of course, there are specialists, experts who study that. But what epigenetics stands for is truly everything on the top, like epi, on the top of genetics. So usually it means how the DNA is represented in three-dimensional structure, so the DNA can be compacted to the extent that it's inaccessible, and DNA can open up in order for other proteins to come in, transcription factors to come in, basically all of these other workers to come in for the DNA to relay the message. which we also call to be expressed. So the gene can be expressed or it can be suppressed. So we can, even now with genome editing, there is a branch of it called epigenome editing, where there are companies and researchers, investigators who are trying to tackle the regulation part of the DNA. So let's say there could be a bad gene that is sitting there, but if we suppress it to extend that it doesn't touch anybody, and maybe it's not necessary so much for the body, then from the epigenetic perspective, you could just suppress it, block it, silence it, and it won't get expressed. So again, in a nutshell, idea of epigenetics and genetics. They are very interrelated because without expression, genes will just sit there in the DNA. But I think the biggest misconception when, let's just say the audience will be talking about epigenetics, is the conception that you could just change any gene from changing your lifestyle. And It's not exactly true. There are 20,000 genes, they're doing multiple different functions. Some are very, very solid evolutionary preserved functions that nothing in the world will change that function. You can't not suppress them. They're regulatory, maybe yet. But also for maybe for no reason, let's say their genes, let's just say even the timing, the wonder of the development of an organism, whether it's human organs or any other animal. So epigenetics plays a role in the each step from the one cell moment when the organism, whether it's your beautiful fur dog or beautiful child, you back in the days when you were one cell, you were dividing, dividing, dividing, and that division then acquired determinants, so cells began to be determined, like all of this is based, like differentiation into different types of tissues from the evolutionary biology perspective. All of this is based on epigenetics, meaning the timing of when genes are expressed and when they are suppressed. To bring it back to the concept as to why I think a lot of times this concept is being misused is that um you know genes like thousands of genes could be response responsive to you changing lifestyle and you know being exposed to different kinds of again environmental triggers whether those are chemicals or exercise triggers, fasting, you know, metabolic triggers. But then there are also a subset of genes that just shouldn't even be touched. And it doesn't make sense. And like, it doesn't really respond to environmental triggers. But with all of that being said, I think, of course, you know, we don't know everything yet. We as a scientific community, and maybe some people who are truly, truly Experts in this niche could maybe be on the forefront of knowing more of what truly happens in the epigenome, in the genome expression, with all kinds of different triggers, especially with aging, which is also a really interesting topic, I think probably for your audience. Overall, this also ties in very nicely in the concept of genetic compensation, which I have worked on in my PhD. It was one of my projects, which basically is the idea that a gene when it is, let's say, something goes wrong in the body, in the organism, evolution has ways of adapting. So even if something is truly, truly, you know, bad for the cell, like a debilitating mutation, there are ways for evolution, for the genome from its own regulatory landscape of how all of these regulatory elements of what we used to believe was the junk DNA to come in and to buffer the system. Another gene could be expressed in order to help. so that whether it's a person or an organism would not have such debilitating disease. So there's always this plasticity in genetic expression just like we talk about plasticity in, you know, from the standpoint of neuroscience and neural networks. It's somewhat similar. Genes are somewhat plastic in the way they could be expressed and it could be transgenerational. So from, you know, Again, from parents through generations, the evolutionary, like this mini evolution could adapt as to how genes could be expressed differently. I don't know if I answered your question. Again, I think I went into a whole lot of other topics, but I hope I gave a perspective of what genetics is, what epigenetics is, and also some of the gray areas.

Andres Preschel: You absolutely did, and I think that a really sweet way to wrap some of this up, not to conclude this topic, but to kind of wrap up this point, is can you maybe illuminate some ways that you personally have changed your lifestyle with the things that you've learned about genetics?

Elena Buglo: Absolutely. I mean, not only the things that I learned about genetics, right? But I think just seeing the studies and knowing kind of like some of the general approaches for what I think is good for being your best self in the best shape physically, mentally, emotionally, spiritually, is one perspective. But then to really know and to adapt, which I think is the message that I would really love to relate to everybody that I speak to who hears this podcast, is that you are unique. There will be, you know, we all seemingly have, you know, maybe 99 point 9, probably, percent of our DNA could be the same, especially as being humans, of at least coding regions, and probably non-coding as well. But there are these variations, and sometimes these variations, if you think about DNA as, again, full length of 23 chromosomes is said to have letters, like 6 billion letters in it, which is something like 100, Bibles and so it's a lot of letters and sometimes just one letter could give an extremely debilitating disease when it's misspelled the wrong way. Other times it could be different misspelling but it gives you that uniqueness. So again, bringing it back to the point, I think I've had, you know, a very interesting path of learning how to adapt or how to adjust my lifestyle. And not until recently, a few years ago, when I've had whole genome sequencing, which I still don't have full data from it, but I've had some panels done. So I found some genes that made sense to me with my genetic background to know exactly what could be not be so beneficial for me from the standpoint of lifestyle. And I can bring up a couple of stories and I think I shared them with you recently as well. I think from a general perspective, of course, like the diet that is close to, I would say a balanced diet. Like I've experimented a lot with diets from low carb and ketogenic and long periods of fasting, at least several days of fasting. I've learned that it was also quite drastic for me. I think with time I've learned that I have some predispositions, which I believe you know, kind of like come out in those, in those kinds of circumstances when there's really, really drastic stress such as fasting. So I've learned to eat a balanced diet. I've learned to adjust my lifestyle to, you know, be closer to minimal calories, um, to not overextend, like to not over consume, but also of course to always have oxygenation, so some cardio in my life, strength training, of course, especially with aging, you know, keeping the muscle mass, keeping movement, but also adjusting my lifestyle in a way of, you know, being happy and doing what I love. I think, you know, you could optimize your physiology a lot, but if you're not truly aligned with your soul, who you are, like what your heart is calling for, you're like not optimized enough in that sense. But I had some stories of when I was, you know, I was experimenting with things like metformin, I was experimenting with, you know, different supplements as well. And I still actually have to adjust and I kind of like go on and off of different supplements, but The midforman story has certainly been, again, one of those examples of my unique background and probably my unique genetic background being revealed because, you know, seemingly it could extend lifespan, like regulate sugar levels, right? I was not diabetic, although I have diabetes in my family and But from genetic sequencing, I found out that I do have a diabetes gene that is associated with, again, people having diabetes. So it's not exactly clear, I guess, not exactly clear from genetic standpoint what to do other than not to eat high sugar foods and make sure that the diet is balanced. I also found another gene that is, basically I can explain this in this example, when there are two mutations that come, one from father, one from mother, and they're bad mutations. killed gene, basically. Let's say when two of them combine, we call them homozygous mutations, and those are usually called recessive genetic diseases. So they pass down from both parents, and parents are seemingly healthy, but the child could be extremely, extremely unhealthy. And those are types of disorders when The people can, children are not moving, they have difficulty breathing, feeding, growing, learning. I mean, they are extremely, extremely depleted and debilitated. But sometimes, which we see more and more often, and this is really something I think is intriguing about the field of genetics and medicine and what we're going for as a field of medicine is not only thinking about a disease when there is, again, this debilitating phenotype or expressed version of a disease, but also when there is partly expressed version of the disease. So it's sort of like a depletion. And in my case, I have one of the mutations, like extremely debilitating mutation, but only on one of the chromosomes. So it came from either my father or my mother, but it could also actually appear just by itself during development. And that mutation, it impacts the function of mitochondria, so specifically oxidative force relation in the mitochondria. And while I don't have a debilitating disease from early childhood, right? As I'm aging, if I go into any kind of, and this is all hypothetical, just stressing that, but I think this hypothetical thinking, we see it a lot more, especially in autism genes and some of the autism disorders and some of the other disorders that, again, they show up later in life during times of stress, during times of infection or extensive exercise and whatever stresses the system that has some underlying weakness, so to say. So for me, it was the case with metformin on top of long-term fasting, on top of my ketogenic diet. And I think I pushed so far that I had terrible consequences that was cardiac in nature, terrible arrhythmia and also some neurological consequences from me trying to use the metformin.

Andres Preschel: So, for example, were you like severely, chronically hypoglycemic?

Elena Buglo: There was some hypoglycemia involved, but primarily I had arrhythmia, I had shortness of breath, I had somewhat, you know, all kinds of like tingling, like very non-specific symptoms for which I was actually hospitalized. And nobody, you know, nobody really tied that to my mutation, but this is my hypothesis. This is my thinking that I think all of those things I was doing, including metformin, which is a mitochondrial, mild mitochondrial toxin, have pushed me, including I had the flu at that time. So I think my system was really at that fragile, you know, spot where maybe another person would be fine, but because of my genetics, I think I pushed it too far. And now I would never take mitformin, I wouldn't recommend it, unless people know their genetic backgrounds. But also this is really useful for me to know, for example, with some other mutations that I've found in my genetic background that, for example, like statins are not good for me, I shouldn't be trying them. There's plenty of people with my genetic background who have been I had some other cardiac consequences, cardiac inflammation from statins. So unless I know that, unless I have really, really looked at my DNA, I wouldn't know these answers. So for me, I think now, since I'm still at the point where I don't know all of these answers, I don't know fully my genetic background, but it's really essential, I think, this point that I would like to get across is that we are all unique. And if you just, you know, using all kinds of biohacks, almost like mindlessly, you might find a spot where it's going to be too drastic for you. Like don't, you know, when you push too far. So it's all about balance and kind of like knowing and learning yourself, learn, learning truly the science behind you.

Andres Preschel: and how that's ever changing. But you know what? So if I got this right, and please correct me if I'm wrong, but if I got this right, basically you looked at your genetics and your family to determine if you could benefit from something like metformin, glucose-lowering medication, which is commonly used by, let's say, biohackers or health optimizers to just keep the blood glucose levels under more control, which can support energy, productivity, mental clarity, longevity. But in your case, while you technically had a genetic predisposition, you weren't living a lifestyle that gave you elevated blood glucose levels, and so you kind of added these things in blindly, hoping for the best. You saw no harm. And on top of that, you were doing a ketogenic diet. On top of that, you were fasting. And on top of that, you had other types of stress. So far, am I getting this right? Because I want to make another point. Does this sound about accurate?

Elena Buglo: Yes, this sounds right.

Andres Preschel: Okay. So, me personally, as a physiologist and with some knowledge of psychology, nutrition, etc. My interpretation of what's going on is like you are certainly glucose deprived and at this point, in order for your nervous system to function optimally and to handle the stress that you're engaging in, besides the physiological stress which is objectively there with the things that you're restricting and then adding something in that is further restricting glucose. Look, glucose is the most efficient fuel source. The mitochondria love glucose. The nervous system loves glucose. There is going to be some dysfunction down the line if you're you know, glucose deprived. The body has to work tirelessly via gluconeogenesis to convert things other than glucose into glucose and that process is really stressful. You need to have technically higher levels of cortisol that come in and convert the muscle, you know, into glucose for example. So it's like this positive feedback loop of like even more stress and more stress and more stress and more stress. And, you know, it doesn't seem unlikely or uncommon that you would have some kind of cardiac issue, right? Because now your nervous system is just like so overwhelmed. So, I think this is so far, again, if I got this right, if I'm understanding it correctly, It seems to me like, man, people should really think about this before they embark in any health-optimizing thing that they don't need to do. You know what I mean? I see so many people doing things like Metformin or doing things like all this HIIT training and cold exposure and fasting. All of these are hormetic stressors and if you're not finding an effective way to recover from that hormetic stress, then you are by definition just stressed. It's not hormetic anymore. Hormetic stress is a good type of stress that should arise from stress under the right conditions where you can effectively recover so you get stronger, you get fitter and more optimized for longevity. But it's interesting to me how someone like you, it's like ironic, right? Because someone like you is like, oh, well, I'm looking at my genetics. I'm looking at my lifestyle history. I'm sorry, my, my, my, my, my parents lifestyle history and et cetera. And so you were under the impression that you're doing the right thing. So if you're, if someone like you is making mistakes, think about the vast majority of people, right?

Elena Buglo: Absolutely. No, absolutely. And, you know, to be fair, I did, like, I found out about the genes down the line, like, you know, years after, a couple of years after I had all those symptoms. And of course, I had, like, many more. But, like, it took me time to figure out. I don't think I'm in the final answer yet. And I think, you know, of course, this needs to be studied, maybe, like, by looking at my medical mitochondria, and of course, collecting more evidence from other heterozygous carriers. So those people who also have maybe just one of those alleles of those mutations in the gene. And even with that, like the genetic background they already have, which includes all kinds of other genes and variations. So I was, exactly like you said, experimenting with thinking, you know, having a good will in my mind that I'm doing something to optimize myself. And to be fair, at that part of, like, as I was doing it, Before the infection hit me, before some other stressors hit me, I had the most amazing, I felt the strongest, the most flexible, and the sharpest in my mind in my whole life. So that's why I was so addicted to fasting, I was addicted to ketogenic eating. It made me feel good for a while, and then some more tweaking, plus the stressors, which are unavoidable, we don't live in a bubble. Of course, with the story of COVID in the past few years, we can see so many other consequences to that. You can be thinking that you're doing, just like you said, something so useful for your biology, for your longevity, but you could be overdoing it, including sometimes over-exercising. It's so important to do your best to be attuned to listening to your body, to know how to respond at a certain period of life to whatever stresses are going on and to make sure that you're also measuring, you're really seeing where it's coming from.

Andres Preschel: Yeah, sometimes the best thing that you can do is less. Like, you know, I have a lot of clients that are these high performers, you know, they're executives and they're athletes and, and they just want to do more. They hope that every time we have a call, they're like, all right, tell me, I want to do more. I want to do more. I want to take more supplements. I want to do more biohacks. I want to do more, more, more, more, more, more, more. Oh my God, it drives me nuts. I love it because the opportunity for growth is so simple in that case and it's to literally just do less. Dude, just be more bored, sleep more, do a little less exercise because all of that, all those inputs can really overwhelm your body and less is more. Oftentimes, less is more. I've actually found, you know, similarly I was doing a lot of fasting, a lot of training and for whatever reason I was still tired all the time and I just couldn't figure out why. And I went through a functional medicine doctor and I did genetic testing and I did food sensitivity testing and I did all these tests and I had all these theories. And you know what helped me the most was eating more carbs. as simple as that. Just eating more carbohydrate. Anyway, so that being said, I mean, I think this is so revealing and so illuminating for so many people. So let me ask you this question, you know, considering that this is such a, again, complex topic with so many interests, how do you think geneticists, people like you, can help us see the bigger picture, whether that's possible now or not. How do you think that genetic testing or how do you hope that genetic testing might be able to show us our life in the bigger picture so we can take action in the big picture and avoid getting myopic about genes here and there?

Elena Buglo: Well, I think certainly, I think not just for, you know, the normal lay audience, but even in the field of medical providers, there is still so much work, even in the field of genomicists and people who actually work in genetic discovery, we are learning so much. And now we have so much more data than what has been analyzed and interpreted. So interpretation matters, of course, it's a big hurdle for geneticists to often know what it actually means. You could have all these variants, you could have different genes that seem to be a predisposition to disease, but Sometimes it's hard to say whether you will develop disease or not, whether this mutation is truly pathogenic or is truly bad mutation or not. And I think it's important to just continue scientific discovery, to continue scientific discovery and to continue having these conversations with just regular people as well as the medical providers who don't usually think that, again, they don't usually think about genetic background so much. Because so many studies are done without any regard to genetic backgrounds or stratification by genetic variation. So if you go to a clinical genetics meeting, everything is about genetics. Everything is, you know, it's like people are in their Kind of like in their tunnel and they think genetics, genetics, genetics. Even if something else happens in life, you know, that is of purely emotional nature or socioeconomic nature, these people would be thinking about genetics. No, it must be some variant that makes you behave this way or feel this way. And then you go to another meeting that has nothing to do with genetics. you know, people, even medical providers, they might be confused if they're looking in general type of disorders, even when you come there with, you know, some kind of infection, some kind of arthritis or any other issues. They won't be thinking about genetics, they could be thinking inflammation or something else, but they won't be thinking about the interaction of that with genetics. So the work that I do, you know, through the, how I work with industry or from the medical affairs point of view, is that it is my job to help to deliver this knowledge that There is genetic variation that you need to be looking for these rare genotypes, but also even beyond that, to be thinking about genetics. For example, when I work for the type of disorders that are movement disorders that show up in childhood, which are often called cerebral palsy. So, it used to be believed that cerebral palsy is the kind of disorder where something happens maybe during birth or pre-birth, and basically we don't know, but there's nothing that can be done. And now with the development of the genetic studies, we could see that something like 40 to 50% of cases of what was thought that was idiopathic, we don't know the origin of cerebral palsy, is actually genetic. And sometimes you really need to know what key goes into which lock. to open that log. So it's kind of like fitting the puzzle together. So there could be genes that are kind of like the wakefulness genes that respond to small molecules. So it doesn't need to be something so drastic to have an intervention. There are genes where literally children could have hypotonia or spasticity, like inability to move with good normal tone in their muscles or when the muscles become too rigid. which could be alleviated by introduction of something as simple as caffeine. So, something as simple as caffeine that could be suitable for this child to be able to move normally. to be able to experience the world more so normally. So knowing, having that precision, having that education, making sure that all of the medical offices have this continuous education, which is, you know, of course is required for all the offices to keep developing their medical education, but at the same time it's really hard to keep up, I think, for the medical system because there's so many discoveries that have been made where you just can't be updated. That's why there's a job like mine in medical affairs where You know, you become kind of like an expert in a specific niche and you can deliver this knowledge because otherwise it's just an overwhelm of information. But of course I think we're moving towards a future where, again, there are databases for all of this. for genetic knowledge. So I think everybody should be trained to have access to those databases to understand. But also genetic sequencing became so much cheaper. If it used to cost, I don't even know how much, million dollars, you know, thousands of dollars. So now it costs hundreds. Now we not only sequence genes that are expressed, but we sequence whole genome. So with that information, of course, there is AI that helps to analyze this information, to interpret it. With use of AI, we can then be able to be more hands-off in understanding that, OK, I can maybe access, I can at least think about genetic sequencing, look at it, and help AI interpret the results. And of course, we still need You know, people like genetic counselors or genomicists who kind of like double check the AI, of course, when it's still not at the point of blindly trusting what we see from data, so to say. So with all that, I think that this would be my answer to your question. I think we just, we need more education, we need more research and just connecting the dots. The information now is out there. We need to do more genetic studies and better clinical trials for different, not just precision medicines that we'd love to share more about, but for regular medicines to make sure that there is some consideration of genetic backgrounds, especially for the kinds of mechanisms of the drug that affect specific you know, molecular mechanisms such as mitochondria, you know, well let's screen out people who have maybe mitochondrial gene mutations and see if that affects them differently. Does it make sense?

Andres Preschel: Yeah, yeah. And so clearly there has to be more education and an important interplay between experts who can look at these things in isolation, but then at the individual as a whole to understand if and how exactly this impacts their life, well-being and other, you know, considerations beyond um, you know, they're this brings me back to a really interesting question that I Heard on a podcast I think it was between Ben Greenfield and I think it was mind pump radio I can't remember but they were talking about how Ben Greenfield did this genetic test and he found that He and his boys and they're all you know, they're a brilliant family For whatever reason they have lower levels of BDNF in their brain and I know that your background is also, you know, you're a neuroscientist and So, they have lower levels of BDNF and so, because he found out they had lower levels of BDNF, him and his boys, every single day, they take like lion's mane mushroom and they pair with other supplements that are helpful for BDNF. But then the guy and the host, and I really wish I could remember who it was, said something like, well, how do you know that that's the right thing to do because what if your physiology has evolved to make BDNF more bioavailable for the lack of a better term? Like, how do you know that you necessarily need more? Like, what if your genetics just work better with less? And, you know, they're brilliant people. So, so I think that alone was, and I think Ben was stunned by that question. And I think most of the listeners are stunned by it too. And I've never forgotten that because it really showed me how much wisdom there is left to unlock and how much knowledge there's left for us to uncover before we can even attempt to answer questions like these. You know what so First of all, I want to get your take on Conditions like these like what would you have to say about something like that? And then I have a really fun follow-up question But what do you have to say about something like this? Like is a is a problem on paper always a problem or it made you know How how much how well can our physiology adapt to compensate for what seems to be an outlier or some kind of underlying issue

Elena Buglo: Well, this is a great, you know, it is a great question and I don't think we know enough. Like I said, there are thousands of genes, so they're not even studied enough. And what I studied, the genes and mutations that I studied really well are usually the extreme phenotypes, you know, that really showed up as disease. For example, you know, for Huntington's disease that is genetic and it is the expansion of certain repeat sequences within Huntington gene where there is phenotype within a specific range of how long this expansion is. So if there's just a bit of expansion, I'm not going to quote, I think maybe like something three to eight, I don't know exactly, of the repeats, then you could be completely healthy. And how is it known? Because of, you know, hundreds of people with this disease screened, studied for years, because it's been such a drastic disorder. And then after a specific amount of repeats, it becomes extremely detrimental. And again, only by knowing the natural history, and even though it's more rare, by studying this very closely and understanding at which age Do you show specific deficiency? How does it manifest? Does it first manifest as, like they say, it could be actually some, it could even show up in speech years before the first movement symptoms, emotional symptoms, deficits of prefrontal cortex arise. So we can begin studying early and early and really, really paying close attention to noticing, you know, Yes, what does it do and what are the people who are similar with these disorders? What do they look like? So it's called natural history, right? So it's been studying still, you know, there are over 7,000 of rare genetic diseases and Some of them are more prevalent, more common. It's usually something that's like one in 100,000 people that show up with disease, on average, considered to be rare. And there's something that's more rare, like one in several hundred thousand. Some diseases are one in 10,000, one in 30,000. They're still rare, but then they really pile up. There's more and more people who, you know, show up because of how much population we have with those disorders. And then sometimes they overlap in backgrounds. So it's not that you could have one mutation. It's possible that you have mutation in another gene that is also responsible for something that's necessary for your brain. So I think probably AI would be the best way to understand all this complex, big picture, this complex, big picture of especially the gray zone that you're talking about, let's say. If it was a debilitating disease, usually, like I said, it could be that two genes from mother and father, two alleles, they need to be completely missing. But they could also be a recessive disease when they're a little bit malfunctional, they're not as good. So proteins are made, so gene is expressed, the protein is there, protein is doing some really important function. And if you think of your organism, your cell, as, let's just say, your house, your household, or like a room in a house. Like, it could be a particular dysfunction, like a facet that's not working, you know, in the kitchen. So if you have, it could be completely that the water is not flowing, and then you, you know, just imagine this in your daily life, it would really affect you. You'd be like, I can't wash the dishes, I can't drink some water. So, all of a sudden the impact is great. But if it's kind of working, so it's dripping a little bit and you can still get the water, so it's not functioning great, but it's kind of functioning, then if you have a party in your house, then that will be the problem. Because it won't be just available for you, but it won't be available enough for other people. So the same is the idea with the genes. Yes, it could be like you're getting by with this amount of, in your example, let's say BDNF factor. BDNF factor is really important during growth. And I'm not an expert on BDNF factor, but of course I know that it's extremely useful from perspectives of aging. And I think it's been studied in some of the like trials or approaches for neurodegenerative diseases, like the ability to enhance the expression of this factor in the brain. And certain molecules can also do that. I believe that exercise, you know, increases the expression of BDNF. So, it is true, I think, for some things like that, like BDNF, if it's a little bit lower, but it's not completely missing, because I think if it was completely missing, then these people, it could be possibly lethal. it could be possibly that, you know, the brain just would not be developed the way it should. So it's possible, it's just like I was, you know, mentioning the idea of genetic compensation, it is possible that the body could adapt somehow. At the same time, it's possible that the body will reach some point at a time with enough stressors, just like our conversation in the beginning of the podcast, where the stressors are overweighing how much the body can compensate. So it is true, it's possible that another gene, and I don't know those genes, but another gene maybe could have similar function. It's possible that if it's a mutation, again, in one of the alleles and the other allele is functional, that the gene would be expressed more often. It would be enough to, again, compensate. And it is also possible that with enough amount of stressors, it could be again infection, viral infection, aging. you know, like something that is kind of like specific to this pathway to the brain could be concussion. Like, I don't know exactly, like it could be something inflammatory in nature that at some point the tipping point is reached and the body cannot compensate anymore. And, you know, it's possible that it could affect the individual. So but with that I think it's again it's just it's such a gray area because everybody is unique in that gray area unless it's something very drastic and very obvious that is pathogenic mutation this like the body cannot go without it or there could also be like I was talking about recessive diseases when things are missing there's also dominant diseases when quite often genes are misbehaving they're making plugs, they're creating amyloids. So with that too, maybe a little bit is okay. But when it becomes too much, then the body cannot deal with it anymore. The body cannot eliminate, the body cannot attack and remove those amyloids anymore. So it is very complex. So I think the right answer would be that we don't know. And you know, this is still a great area, great area.

Andres Preschel: So the body has a certain capacity to buffer a lot of these things out. And all of us, I mean, none of, no one on this planet is perfect, meaning nobody has the ability to buffer every single thing out. And there's sometimes issues that are real issues that are beyond that threshold where you need to get help or you have a rare genetic condition where you need to, I don't know, edit the gene. But I'd say, I think so far we can agree that A healthy lifestyle within reason is going to support your body in most of its ability to perform the right actions at the right time to spare you from some of this damage, to mitigate some of that damage. So that can be something as simple as, let's say, optimizing your recovery through sleep and stress management and then eating whole nutrient-dense foods and exercising within reason, not overdoing it. I think that most people tuning in, and I think you and I can agree that Alright, we have the bulk of things that most people can do right. Let's put that aside for a second. Back to this analogy with the water, for example, right? You have this faucet and it's dripping and it's not an issue until you have a lot of people over and then I have a lot of dishes to clean and now you don't have enough water. So you have piling dishes, right? I'll give you another sort of analogy in a way, something that we can explore. So like in my apartment right now, I actually have an issue with water pressure in my sink, okay? So like, like if I go next door to my neighbor's place, like his sink is so much more capable than like his, his faucet, he has amazing water pressure and it cleans plates so fast. I, while I have a bigger apartment, the kitchen wasn't renovated and this isn't, I'll make sense in a second. The kitchen wasn't renovated and I don't have a dishwasher. He has a smaller place, but he has a dishwasher in addition to a really nice high pressure, you know, sink or faucet or whatever you want to call it. So, what do I do? I take my dishes and I put them in his place, okay? But here's the point. What a nice neighbor. Yeah, he's the best. Hadiel, thank you. Love you, bro. Thank you for cleaning my dishes. Trust me, this analogy has nothing to do with me putting my genetic issues on him either, but here's the point. While that's an issue in my place, in the sink, The water pressure in my shower is awesome. Like, I love my shower. It's so good. And I have reason to believe that if I improve the water pressure in my sink, that the water pressure in my shower would probably go down, right? So the point that I'm trying to make here is I want to explore this theme that sometimes our deficits on the other side, you know, if you flip the token over, it can be a strength. And I know there's a lot of cases where like maybe you're trying to optimize for a specific gene, but there's a trade-off, right? And even when cells are dividing, and this is with my limited knowledge and experience in genetics, like I can't remember 99% of what I learned in my genetics course. But I know that when there's like this crossover effect right and different genes interact and you know, whatever like that can be a strength and a curse at the same time and So if we're looking at human beings and you know being so individual being so authentic you know if we look to CRISPR and editing genes is like this like wow like this is the answer and How much of our strength and our unique ability and our authenticity are we dismissing as a result?

Elena Buglo: Well, then, you know, the devil, the devil is in the details. Then we really, I think, should be answering the question of what exactly are we trying to do with which gene? You know, what exactly are we targeting? What exactly are we talking about? So if I understand you correctly, I guess you're trying to say that if we were to try to lean on CRISPR in order to biohack or optimize ourselves as humanity, could we be then at a point that we've missed some of the, again, the benefits of our so-called deficits, right? Is that something you're saying? I think this is also a really great point and look, it really It's kind of like we talk a lot about, even when we are developing therapists, let's say, or have days looking at therapists, we think, what is risk to benefit ratio? And it's your best estimate. I think it's very clear when a child is born and cannot move and cannot breathe and cannot perform any important life function. that it makes sense to use CRISPR, to utilize this technology in order to help the child. For example, if it's missing a specific gene that needs to be made to add this gene in a part of the body or in the whole body, or edit it out, edit out the mutations. We have now technologists and scientific communities, biotech community to go and to approach in their clean matter, the editing of specific mutations with base editing or prime editing, and even epigenome or RNA editing, where we can help with those extremely, extremely debilitating cases. And then I think what the future holds, and I'll get back to your point, to your question, but instead of dealing with the consequences, which of course is a big ethical conversation right now, and it's a very controversial conversation, but we should be really dealing with a much cleaner, with a much cleaner approach, basically just knowing Let's say if you know that you have a mutation, for example, it's in your family, but even we can come to the level of technologists when we can screen embryos, screen eggs, fertilize eggs to see which mutations could arise. Because not all mutations come from parents. Mutations come at random during development. So something could go wrong during DNA replication, it would cause a mutation. It could also be mosaic mutations sometimes in specific part of the body or the system, like the brain or the gut, you know. So they're definitely now the technologies that are actually capable of screening it out at very early stages. And what I think if we ethically and from technical standpoint come to a place where we are certain about safety of utilizing CRISPR to prevent any chromosomal rearrangements, any kind of dangers that could come out with the intervention of the other cutting or flipping the base pairs in the DNA, then we will really be talking about the editing out of those diseases in a clean matter, the first one cell stage, so that the whole body develops in a healthy way. But then what you were talking about is something that could also be quite, you know, disturbing diseases that they could show up later in life. And again, I think it's also an interesting philosophical question of what is even disease, you know, what kind of malfunction? Because at some point, again, we enter in this gray area where there's some deficiencies. It could be deficiencies in energy levels and psychic functions, cognitive function where you are just not very sharp, you know, and those could also arise from genetics. Like I said, a lot of autism genes are known to now arise from genetics, different malfunctions of hundreds of different genes. And then with that being said, I was recently listening to George Church from Harvard, who was talking about his condition of narcolepsy. And he had this great point. And he, of course, has also some of the most philosophical and cutting edge, very practical views on both genome editing, future of genome editing, being an advisor for many companies, founder of many companies in this field. So he was saying with him experiencing narcolepsy, he wonders if with the same question that you have asked, that even though sometimes this could be intrusive for his daily activities, like he could just go, you know, asleep at times when he doesn't want to go to sleep. kind of like his body would force him into that state. But then he also derives a lot of creativity from those states, from in-between states, from states, you know, again, that surround the state of sleep, which we also don't know enough about, you know. There's a lot of enigmas around that. So I hear your point and I think I would just echo the same idea that we don't want to necessarily target all kinds of genes and also we're really still early on in targeting of the gray area genes and diseases. because of all kinds of fluctuations that can again rise from genetic compensation or just actually finding out that this gene was important or it's too much of the gene that was delivered, you know, whatever. There are different scenarios in which genome editing could be introduced and gene therapies could be introduced. But it is very possible, just like you said, that we could be eliminating some of the uniqueness in unique phenotypes. Even I know from some of the autism researchers in the field, and I'm not, again, I'm not a representative expert in that field whatsoever, but there's a new movement of looking at autistic people, patients, which is calling them neurodiverse. And neurodiversity is important because maybe you're missing some function that you think is, everybody else thinks that is important, some kind of logical, rational thinking, or recall of a specific, you know, specific memory function. But you could have all these other abilities that are enhanced. And it is true, it makes a person unique. Of course, maybe it also makes a person, you know, have some hardship with daily activities of daily living because of the way the society is constructed. But regardless, if the adaptations could be made for the person is, you know, I think there are definitely many people in the field who think that we should just leave the nature the way it is. But there is still not so much, not as much gray area with the debilitating diseases and targeting those and helping. from that perspective. But then there's also a lot of interest from people with money or people who are just more innovative thinking, who don't have any problem or any care for those debilitating diseases. There's a lot of interest to enhance cognition, enhance longevity. you know, have designer babies, have, you know, more muscle and less fat. Have designer puppies. And this could also be designer puppies, designer anything. And, you know, have basically you could use this technologies now. And I think there definitely could be something under the table that is happening with, you know, development of such technologies towards that kind of future.

Andres Preschel: So that was, I mean, thank you for doing the science justice and taking us through your perspective and elaborating on it in such a way that not just shows us the pros and the cons, but inspires us to look at the bigger picture and to have an appreciation for nature the way it is. You know that I treat myself like a human guinea pig, so I'm going to take you through a little story that I think you'll enjoy, and we'll maybe show people how maybe sometimes living nature the way it is might be the best idea. So, I suffered with ADD for a very long time. I had trouble focusing, being productive, doing my homework, being a good student in class. I took medication to help me get by. I'm so grateful for it. My parents, you know, were managing all that great. A couple of years ago, I mean, then I embarked on my, you know, I ditched the Adderall, I embarked on this, you know, lifestyle medicine journey and applied neuroscience and physiology and nutrition, you know, whatever. And I started feeling great, stepping into my excellence, being authentic, and it's been great. I built a business and a brand out of that. It's the reason why we're on this podcast. A couple of years ago, I did a genetic test with 23andMe, and on that test, I discovered By the way, let me just paint the picture here. I was on a trip to Colorado with my best friends, and we were about to climb this mountain, and we had very poor cell service. And of course, I got the results while we were in the car. Cell service was terrible, and I just happened to get a glimpse of the results, and the results said that I have a genetic predisposition for Parkinson's, and that I'm at a slightly increased risk for early-onset Parkinson's, which was at that moment in time, absolutely devastating for me. It's like I got a life sentence. I was so devastated by that. And I didn't know what to do. I was suddenly just completely overwhelmed while I was on this trip with friends that I was supposed to be enjoying my time, being present, climbing this mountain. And what did I do? I went crazy. We got to the base of the mountain, and with terrible cell service, I was spam calling my mentor, Dr. Wesley Smith, who's the head of nutrition and physiology at UM, who's just a brilliant guy. Kept calling him calling texting freaking out sending him pictures. Like I'm like overwhelming this guy with messages. He finally picks up and he's like trying to get me to calm down and then self-signal went out and all I had to do was Climb this mountain actually on my own because my friends just you know, they couldn't wait for me any longer They went up so I'm alone climbing this mountain reflecting on how terrible this basically what I assumed to be a diagnosis was I was so devastated I get to the top whatever it's Anyway, I kind of let my feelings subside a little bit, and then we got back in the car, cell signal improved, and I started to dig into some of the research. And what the research stated was that with this gene, And if you have a diagnosis for ADD, you have a tenfold increase now of early onset Parkinson's. And if you took medication on top of that, it's like a 100 to 1,000 fold increase in likelihood of early onset Parkinson's. So it just made it so much worse. I don't think I've ever been so stressed out in my life. Then I spoke to a friend of mine, she works with Parkinson's patients. She laughed at me on the phone. She was like, Andres, you're a living example of everything that you should and need to do to prevent Parkinson's. And that alleviated some distress. But then I had the chance to actually meditate on this, like really deeply meditate. And what I realized was that in fact, yes, I live a life that helps prevent all this. I realized, looking at the dopamine response, right? Like, Parkinson's can be, I guess, very simply described as very low dopamine levels. Let's just make it, if it's okay with you, I know that this is your area of expertise, let's just, if it's okay, let's… Let's define it as very low dopamine. If you're taking something that is constantly upregulating dopamine like, you know, Adderall and you're sleeping in the synapse, now your sensitivity to dopamine decreases. And, you know, if you have ADD, you have even lower dopamine or you have trouble focusing. But what did all this actually mean to me? This problem that I had is what actually motivated me to pursue a career and a path that was as authentic to me as possible and it just so happened to be that it was in health and fitness. What does that mean? I wasn't motivated to do anything else because I think technically my dopamine was so low. The things that I actually wanted to do are things that I was genuinely interested in like fishing, video games and science. Those are like my three things. And those are the things that always saved me and helped me feel better about myself. And I don't think if I didn't have a dopamine issue, I think I would have probably pursued a path that wasn't authentic to me. I would have just maybe gone to med school and done whatever my dad and grandpa did because they inspired me. But I think I would have been very unhappy. And plus, I would have had to continue to be medicated on top of that. And I wouldn't have been this healthy guy. So, I'm now in a position where I'm so happy with who I am and how my life turned out to be. And if I didn't have the opportunity to reflect on how terrible this news was, I wouldn't understand that the same deficit that I had was the reason why I embarked on this authentic life. And this authentic life gives me that endogenous production of dopamine that I think is literally saving me. So that being said, I know this is a bit of an extreme example. That being said, I am a fan of living a biologically consistent life and trying to do right by nature. But I am so just I'm so interested in what genetics have to say and what the what the future might look like so that people can get the best of both worlds, so that they can be authentic and so that they, while still doing right by their body and making sure they're protecting themselves. Anyway, I wanted to bring up this story and now I have a fun question for you actually. I have a billion dollar idea. You ready? Multi-billion dollar idea for us that we can maybe pursue together. What if we created a genetic dating app? Okay. This is like not a super serious question, but imagine if you were able to, um, sequence people's DNA and put them on an app where based on the combination of their DNA, we can optimize for not just a loving relationship. I mean, I'm sure there's other qualities that we can add in there besides their genes, but making sure that when they have a baby, that it's as healthy as a baby as can be. Right. Like I think it's realistic. I think it's possible. But do you think, going back to this theme of nature versus what does the science say, what does the science want, that this would be a good idea or a terrible one?

Elena Buglo: You know, as you were sharing your story, I could not have imagined that you would lead into a question like this.

Andres Preschel: I know it's a new turn of events. I know I went from a very sad, depressing to very inspiring.

Andres Preschel: From a sad Parkinson's story.

Andres Preschel: I probably sound like a psychopath at this point. But, but seriously, you know, I, at the end of the day, even if I get Parkinson's, you know, God bless, I have lived a great life even at, you know, the ripe age of 26 years old. Um, the point is in a nutshell, sometimes nature wins. Um, but, but, but my follow up question is, you know, do you think that we can use this to maybe curate an experience for people when it comes to dating and reproduction that can really give them the best of both worlds. So let's say we had a dating app where people could come in, they could share their gene pool and their genetic sequencing, you know, whatever, and we could optimize for the quality of life of the baby so that technically speaking As far as nature goes, they're in good hands, they're in good shape. Therefore, they're not going to have to worry about things down the line. I know there's more to genetics than just what your mom and what your dad have in their gene pool. There's mutations that happen due to lifestyle circumstances, due to just simply self-division. But if we can at least get those two bases covered, do you think from that perspective it would be a good idea or maybe a harmful idea to pair people based on that reproductive capacity, if we're optimizing for the reproductive capacity?

Elena Buglo: Well, it is an interesting idea. And first of all, you know, sorry to hear about your story at the same time. I want to also give you reassurance that slightly increased risk, you know, the way that 23andMe reports those variances, not necessarily that you would develop that and I don't know specifically looking at which gene and which mutation but I know that Parkinson's is much more than genetics so I think you are definitely doing everything right that you are of course not using eterol and you know sleeping well and optimizing your health and nutrition, your movement And also living life of purpose, doing what you love and, you know, being involved into the physiology science and continuing the fishing and doing, again, other things that you love. And that it fuels you at the same time with that knowledge. And I think on top of that, to extrapolate, I think we're getting into an interesting philosophical debate, again, beyond some of the people saying, are we playing gods by using CRISPR genome editing and other people saying, You know. Let's just say in my perspective, like everything is God and God gave us this tool. So we are using nature and we are collaborating with nature. And yes, sure, we are playing and we're learning. But the same way we play with fire, which came from nature and electricity that came from nature, you know, when we really using the technology and harnessing it in the best way possible, then we can, again, proliferate as cultures, humans here on planet Earth and hopefully to the better of the planet. As far as genetic dating, I think, and I don't know so much about this subject.

Andres Preschel: That was such a perfect way to distill everything that I just said into two words. Genetic dating.

Elena Buglo: It's perfect. So as far as genetic dating, and again, I think I don't know so much of that research that already exists. I think nature already predisposes us to be attracted to people who are somewhat different, but also it can confine us into, again, socioeconomic circumstances. to sometimes be in the situations when we are creating those diseases and you know for example incest or the consanguineous families when cousins are marrying Usually something is recessive in family, some of the parents are carriers and then all of a sudden the pool goes back into the bottleneck and here we get a child with both mutations that haven't been dissolved in the genetic pool. That's why we have a lot of genetic diseases in populations that are tribes. Some of the indigenous people who live isolated and they just continue, you know, continue having babies with some of the other, you know, remote relatives or some of the other types of similar genetic backgrounds. But then nowadays, of course, we have you know, living in modern society, people are dating people of very different genetic backgrounds. And I think, again, I don't know so much about the science of attraction, but it's often that the opposites attract. And it's often that a person from a different genetic background from a different social, like from different ethnical background, from different country comes and all of a sudden they become the center of attention because in their country they look just like everybody else. In the other country they become unique, they become more exotic, they become more attractive and I think there's something about both dopamine system that looks for novelty and looks for something, you know, for thinking about that there's something more to eat than it seems. So by the imagining that there is again, something more again, exotic, something more interesting about something that is novel and different. on top of already existing, perhaps, kind of like genetic predisposition of us thinking. And I know some of it actually comes from even smell, not pheromones, but something about the smell. Again, don't quote me on that. I'm not an expert on those studies, but there's something unconscious, subconscious that attracts us to people who could be a good match genetically. But with that said, we can see that it doesn't always happen. And even sometimes people from different ethnical genetic backgrounds could still come together and have a child with mutations that expresses a debilitating disease. But all of that to say that this is like when we do combine different backgrounds, ethical backgrounds, when we are attracted, this is already nature's way of trying to disperse some of these mutations so they don't propagate.

Andres Preschel: Diversify the gene pool.

Elena Buglo: Exactly, exactly. But, you know, I feel like modern dating is so complicated that maybe you could design babies, you could CRISPR babies, you could order babies maybe potentially in the future that just come in a package. You know, of course, I'm exaggerating this point, but dating is just so much more complex that I feel like when people are told that they're a good genetic background, like what does it even mean in a way? You know, it could be like people could be athletically similar or they're actually different enough to kind of like to have their backgrounds mixed in a nice way, but people look so much more out of dating in order to raise children, you know, of course, it should be based, I think, on values and some other, you know.

Andres Preschel: Maybe our genetic dating idea can just be a filter within the dating apps.

Elena Buglo: It could be filtered. Exactly.

Andres Preschel: Good point. Hey, look, you mentioned something earlier about this, like, foreign, you know, the novelty, you know, and how that may have something to do with diversifying the gene pool beyond our conscious mind. In the wise words of I never thought I never thought I would be quoting this person, let alone on this podcast. The wise words of Kodak Black, who is a rapper. If it ain't foreign, then it's boring. OK. He's he's he's this is this is this is hilarious because he's talking about, you know, having these foreign girls. It's like a flex. Right. For the for the lack of a better term. But if there's truth to it, there's truth to this. It's as simple as that, but there's truth to it. Foreign partners are exciting. They're gonna help us broaden our gene pool, and then the intelligence of our physiology can then decide, all right, what genes are gonna be in this new, beautiful baby? Oh, we'll have this amazing gene pool, all these amazing qualities to choose from. Let's choose the best ones under, assuming the right conditions. Right. So maybe the best dating advice that you and I can give so far is, Hey, go to a foreign country and be that novel outlier. And, uh, odds are you'll be very motivated and the, um, you know, the folks over there will be very motivated to bring you in as well. So that might be one of the best ways to get the attraction satisfied. All things considered.

Elena Buglo: Well, it's a good point, but at the same time, I think what I was referring to is kind of like, it may appear as more attractive, but actually it's not necessarily. Like, just because it seems exotic, because your dopamine systems are telling you that, oh, because it's foreign, that is amazing. You know, then you get into, I think, like you're really mixing cultures, which also could be really great, but you could be not having the same values. You could have different ideas about finances or God or whatever it is.

Andres Preschel: Relationships are more than just genetic compatibility. Much, much more than that. And in fact, maybe you are genetically compatible, but because you're so different in other ways, that could then create stress and therefore mutations that outweigh the pros. Right. So awesome. So I guess we will not be creating a dating app. I was ready to partner up with you. I had the NDAs ready as well.

Elena Buglo: Maybe with AI, maybe AI could analyze this much better and maybe there is more than correlation in this idea. So maybe it is possible that actually people attract more on some level of genetic attraction. I'll be curious to see, but I don't think it's the top priority probably for utilizing the genetic data. But who knows?

Andres Preschel: Well, okay, let's see in what direction the health optimizers head within the next few years as we reveal more of this wisdom through CRISPR and gene editing and such. I know that we're short on time. How much more time do you have or are you totally out of time for today's show?

Elena Buglo: I could have another 15, 20 minutes.

Andres Preschel: Okay. I think I have another 10. Um, cool. So I know that, you know, your background expertise, um, you have, uh, you, you've done a lot of work with mitochondria and if I hear the word mitochondria one more time on social media, I think I'm going to delete my Instagram. But, um, I'm curious, you know, with your knowledge and expertise and, and just the, the specific knowledge that you have in this field. How do you understand and interpret the function of other organelles in the cell? Because I think there's just a big obsession with mitochondria. And at this point, I understand the mitochondria powers everything, but what about the other organelles? What is there to say about them and their essential function?

Elena Buglo: Well, they certainly are extremely important. Like everything is important within the cell, of course. And, you know, evolutionary speaking, it seems like mitochondria came on board at some point of evolution. But of course, before mitochondria was incorporated into a cell with a nucleus, the cell existed without it. But it's an extremely efficient system of generating energy and it has a lot of other functions, including kind of like in a way, cell destiny, decision of the cell to survive or to be killed. But all other organelles, everything is important. It's just like a little city, right? Earlier I was giving an analogy of having a household, but I often think about organism as something like being a city. So there are all these important functions, for example, function of trash trucks that come and pick up trash. And if there was at any moment, you know, for example, here in Florida, in Miami, when there are hurricanes, you know, and nothing is working, there's no electricity, the trash is not being picked up. Or maybe the nutrients are not being supplied from the stores. Any of these functions being inhibited would be a huge problem. So, there are other organelles that of course are doing this job and they are extremely debilitating. Like lysosomes, endosomes. Well, everything.

Andres Preschel: But I think in this case, taking out the trash, the vacuole for example, you know.

Elena Buglo: Right, so the lysosomes also be taking out the trash. the whole like pathways of how things are packaged, recycled, everything needs to be functional. And if you, if I could give kind of like an example of what it really looks like, I think if you Google any of the videos of the animation, molecular animation of what happens within the cell, it is just mind blowing. There are things that are like, you know, walking on the like, on strings and things are being picked up and transported and then things are being encapsulated and delivered and then there's a bunch of proteins like there's so many proteins on top of both the mitochondria like channels and other different signaling proteins. There are so many different proteins on the membrane of the cell that have all these important functions. They're proteins and they're basically proteins that are important in cell adhesion so that the cells could communicate with each other and could be in contact. There are proteins that are structural that maintain the shape of the organism. So it's not just the organelles, but in general, the spectrum, this orchestra of all of the tools that are necessary for life, for example, all of the things that are needed in the city for it to function. There has to be stores, there has to be supply of energy, supply of nutrients. Sometimes there has to be a person, like a cashier, who needs to be there. For example, some again, transport proteins that shuttle things across membranes. And there are other proteins and organelles that I said that have clearance function and removal of of the trash function and they're debilitating disorders that come with any of these organelles. It could be like hundreds of different proteins that could be important for that specific organelle, whether it's a lysosome. again, or some structural proteins that have nothing to do with mitochondria, but will show up as an incredibly drastic, terrible disease if it is not functioning properly. So, for example, we have a bucket of lysosomal storage disorders, so disorders of lysosomes, There are things, again, when they get too sticky, for example, some of the structural proteins, they are not functioning properly that maintain the shape of the cell. And often, for example, neurofilaments maintain the shape of neurons. They could be just like these big lines. that are necessary both for some of the transports, almost like rail tracks, railway tracks, that are needed for other proteins to both use them for transport and at the same time for just maintaining the shape of the cell. And if the shape of the cell is not there and this is malfunctional, like this structure is not working, then again, it could be neurodegeneration, it could be that energy is just not being delivered to the ends of neurons where it's needed, or like neuromuscular junction is malfunctional, you know, as an example, but there could be so many other problems when it comes to, again, anything that's beyond mitochondria.

Andres Preschel: And I mean, I know that there is so many different ways that we can look at each individual organelle and try to find a way that maybe we can optimize for it. But the reason why I get frustrated about just mitochondria being everywhere, you know, it's like there's I don't know. I just don't like people getting myopic about certain things But I know that they're generally when we recommend something that's good for the mitochondria for one organelle Generally, it's gonna benefit our system as a whole. And so that's what I do like Now I know sometimes people like to just go with whatever feels and sounds novel or whatever Is sexy everyone wants to be don't have more energy so we focus on something like that and I guess in that sense it makes sense, but

Elena Buglo: Well, just to build up on that though, the reason why it's been brought up so much then in both longevity field and there's a lot of all kinds of different disorders to a bucket of disorders that come arise from mitochondrial dysfunction or they mitochondrial dysfunction accompany other types of diseases basically when it comes either as a consequence or, I don't know, co-appears during the process of pathogenesis of disease. But mitochondria, again, being this really efficient energy system, it provides energy from all of the other cells, all of the other organelles to work. So because some of them, they actually require energy for their function. That's why it is so tightly linked, you know, and kind of like interlaced with the functions of the other organelles.

Andres Preschel: No, for sure, for sure, definitely. If you can optimize for the mitochondria, then you can optimize for your body in a way. Well, I'll tell you what, we've covered a lot on this episode. I would love to have you back for a part two and I would love to do it in person since we are neighbors. I know this time we had some… technical difficulties and we couldn't do that. But before we hop off, I'm wondering, aside from what we've already covered, what is something that you think everybody needs to know about their physiology, considering your specific knowledge in genetics, neuroscience and mitochondria?

Elena Buglo: So I think I would like to I would like just to reiterate the point that I have brought up earlier and to share with people just even the thought of both their uniqueness and uniqueness of people in their life. And it doesn't have to be genetic uniqueness or the genetic variations plays role, you know, there again, it could be. It doesn't need to show up as something very clear, like, oh, this person is completely, you know, having a disease or not able to be normal, but it could show up just very subtly, something that is non-specific, again, kind of like they're vague, like they say vague symptoms. It could be that the person doesn't have attention like you do. It could be that someone, your loved one is better at other things such as, you know, going on kind of like the neurodiverse spectrum. They're better with doing something with their hands versus something with the computer or with some cognitive intellectual work. So treating people and accepting people kind of like both the way they are and also just even thinking in the back of your mind that it could arise from their just unique background, whether this background genetic or it's something that is, you know, a social background, the way they were brought up, something that affected them during development, during their childhood, during their life. Or it could be again an infection that long-term shows up as lack of energy or even usually psychiatric issues, right? Or like something that right now we're finding out more and more like gut disorders that again show up a lot through emotional disturbances and irritability. All of this, you know, we are very deeply intertwined with our physiology and our minds and our kind of like the best self. is also intertwined with our physiology, like the moments when we can be our best. If you're judging other people by how you feel, how you experience reality, even you think that they look exactly like you, they look healthy, they are muscular, or they are young, it doesn't matter. I think we really need to be more accepting and listening to others to know that their life experience can be different. You know, there are types of disorders that, again, they can not show up until much later in life, and they could be so vague that only in times of crisis, such as, like I said, starvation, fasting, or exercise, or infection, psychological stress, all of a sudden it shows up. And it could be as simple as, for example, like uric cycle disorders, when there is a protein breakdown that triggers an event where it doesn't necessarily need to be like nausea or you know crisis that the person needs to get to the hospital but it could be just this kind of like vague symptoms of irritability or weakness. So being able to be more accepting, not telling people Kind of like giving advice without understanding and listening to them of what exactly their life experience is, what exactly they feel in their body, and how they respond to those kinds of general advices of exercise more, or you know, you should just eat fat, so you should just eat meat, versus no, you should eat carbs, or you should go vegan. Already with that, I think it would be something that I would love to be remembered from, kind of like everything that I've learned about knowledge and having had self-experimentation, you know, and pushing it too far and still, I think, being in awe of mystery, of my own uniqueness, my own background, my own life experience and continuing to parse it out. I think continuing to have wonder about ourselves and people around us, animals around us, you know, all of the life around us and interconnectedness of life and continue to have an open mind. And again, I think this is the most scientifically The correct approach is continuing to challenge some of the assumptions that we came with into our exploration of reality and continuing to keep the sense of wonder and knowing that we don't know all of the answers, but probing those answers and exploring them every day.

Andres Preschel: Wow, Elena, I can't thank you enough. And this is a topic that I'm extremely passionate about when it comes to intuition and authenticity. And I'd love to explore maybe on the next call a little more in depth how our genetics and maybe the way that we test our genetics can help us reveal our intuition, our intuitive process, and just speaking on behalf of what makes us authentic. So I know we have to sign off now, but I can't thank you enough. This was so much fun. And I'll see you very soon.

Elena Buglo: Awesome. Thank you as well. I'll be super excited to talk more about intuition and all kinds of kind of like genetic underpinning of the intuition and cognition and consciousness, because this is like the subject I'm really passionate about. And thank you so much for giving me a chance to share more about my perspectives and my knowledge and can't wait for the next one.

Andres Preschel: My pleasure. We'll see you soon. So that's all for today's show. Thank you so much for tuning in today. For all of the show notes, including clickable links to anything and everything that we discussed today, everything from discount codes to videos, to research articles, books, tips, tricks, techniques, and of course, to learn more about the guest on today's episode, all you have to do is head to my website, AndresPreschel.com. That's A-N-D-R-E-S-P-R-E-S-C-H-E-L.com. and go to podcasts. You can also leave your feedback, questions, and suggestions for future episodes, future guests, so on and so forth. Thanks again for tuning in and I'll see you on the next one. Have a lovely rest of your day.