Hi everyone, I’m Dr. Sanjeev Goel and this the Advanced Antiaging Technology Summit. I have Dr. Mansoor Mohammed with me. Hi, Mansoor, how are you?
Pretty good, and yourself Sanjeev?
Very good, so I’m just gonna give you a little, I’m gonna do the bio. You have a pretty extensive bio here. Dr. Mansoor is the chief scientific consultant at the DNA Company, a leading and innovative provider of comprehensive function genomics testing and consulting, and an industry first individualized customized supplements. Under your guidance, the DNA Company is pioneering the term fluency and the language of DNA, and it’s revolutionizing the use of genomic testing towards optimized health. You’re considered a pioneer in medical genomics, has been a recipient of multiple academic and industry awards.
He is the holder of several patents in the general fields of molecular diagnostics and genomics research as one of the most sought after national, international, conference speakers in the genre of personalized medicine. So, yeah, I’m so thankful you had some time for me today and I think this is such an interesting field and I know our viewers are gonna love it. I’ve spoken to you before. I have a couple of questions, but maybe let’s just start with some of the basics, like what is the genome? So we can kind of get them up to the level that we wanna get them to. So let’s start with some of that basic stuff. Tell us a little bit.
Sure, you know, one of the things I like, Sanjeev, and I’ve had the pleasure of sitting with you and the awesome way that you view medicine and you view the human body. And I think from that perspective, getting a definition of the genome, what is the genome? It’s the operating manual of the human body. So if we can think of it from that perspective, you know, we all have a basic understanding that we inherited these genes, that we have this inheritance that make us quote unquote, look, sometimes even behave like our parents. And we sort of look sometimes more like mom’s side of the family, or dad’s side of the family. And we may even have certain traits, behavioral traits, quirks, personality, you know, things that define us that someone can get, boy, that’s just like your uncle.
That’s just like your aunt or your grandma or your grandfather. So what does this mean? It means we understand that we inherit certain things and this inheritance which comprises our genes and in totality, our genome, that per what I’ve just said, that genome, that thing you’ve inherited contributes and in some cases defines the way that your body behaves and looks, or I should say the way that you look and behave. So, in other words, we get the concept that, you know, this nose is more like my mom’s, like my hair type, or my color’s more like my dad. But what we need to understand is that your genome in conclusion, controls not just your outward form, but your inner form, it controls or it contributes significantly to how your cells behave.
So in conclusion, your genome is this amazing operating manual that you inherit, that defines or contributes or spells out how all of those little inner workings of your cells, the efficiency with which you do this, or the inefficiency with which you do this, that’s your genome. And that’s why it’s so integral to the type of amazing practice that you practice which is this personalized precision antiaging medicine. Because to know the genome is to know the capacity, inclusive of the efficiencies and inefficiencies, the optimal abilities and suboptimal abilities of the patient that you’re dealing with.
So I know that you run DNA Company which offers these functional genomic testing so people can find out about their genome. I mean, people can also go to 23andMe and various other places. I know there’s a difference. I want you to kind of explain to the viewer what’s happening to DNA Company different than when you go to 23andMe.
Indeed, you know, actually just gave an interview with another incredible personalized precision medicine doctor. And she said to me in the interview, she goes, you know, Mansoor, I did 23andMe before I did, she had done our testing. In fact, she had done our testing simply as an interested clinician. And after she got her results, that was when the sparks sort of the, you know, the real moment of whoa, okay, this is different. And so she came to us having experienced what we offer. So what is this difference? And in her own words, she says, you know, I found out in my 23andMe that I was more likely to have a unibrow. I found that in my 23andMe that I was-
You know like, coriander maybe.
But she actually said, I found that I was more likely to be one of those people that can smell asparagus when you eat it in my urine. And she was laughing in the interview with me. She goes, well for the first, you know, I knew that was gonna be the case. I just had to look in the mirror when I was growing up. And for the second, equally, if I was inclined to it, I could smell my own urine and determine if that was the problem. The point being 23andMe has done an incredible service and continues to do an incredible service by what? By making genetics and genomics and the persons, you know, the coolness, they’ve made genes and they’ve made genetics cool. And they’ve made it the topic of a coffee conversation and dinner conversation.
And I think this is a good thing. I think that by letting people know that, look, there is such a thing as your genetic manual. There is such a thing that you’ve inherited this awesome way in which your body works and learn about that. So they’ve at least opened the door to that coolness. But what do we do differently? Well, clearly, and I say, you know, if you wanna know the color of your eyes or the type of hair you have, go look in the mirror. What we wanna do differently is we wanna get and here’s comes that word, and which is what defines what we do functional. We wanna read the human operating manual with the perspective of putting aside the cool factor of these things we’ve just mentioned.
But I wanna know, I wanna know for myself, and I wanna know for my patients and for the people that come to us, I wanna be able to tell you when you get exposed to certain things in your life, certain environmental toxins, when you eat certain things, what are your metabolic processes? How is your body more inclined to making the hormones that are so vital to your optimal performance? How was your body more inclined to absorbing and transporting the nutrients that are fundamental and pivotal to optimal health? What forms of those nutrients are you more likely to respond to? I wanna be able to tell you something functional, operational. I wanna be able to tell you, well, I want you to be able to tell me what are the top 10 things as you’re going about trying to optimize.
‘Cause you know we live in a time where access to good nutritional information. I mean, we have the whole spectrum, good and bad nutritional information. But the point is we live in a time of data, and we live in a time of access to information. And even one of the silver linings as sad as that might sound of the pandemic is online information is becoming rapidly available. Health information, I’m speaking of, to the consumer. So good, good. We live in a time where health information, the good, the bad and the ugly of it, the intelligence and the unintelligent of it, is available, fair enough. But what we wanna do is we need to realize that it’s not a one size fits all that anyone who’s pursued health, anyone who’s been in a fitness program with their peers and their friends been in a nutrition program at their fitness, you know, with their peers, they’ve realized that things that might work for some may not work for themselves.
So they realize this concept of individuality, personalization. Once we enter into the realm of individuality and personalization, we enter into the realm of your unique genetic operating manual. So what I want a client to tell me is I want a client to tell me, what are the top 10 health goals that they’ve been working towards? What are the things that have seen to be the Achilles heel to these goals? What have they attempted and failed at? What have they attempted seeing it work for others, eating habits, fitness habits, antiaging goals, that they’ve tried but it didn’t quite work for them? And what do I want from the human genome? And what does the DNA Company give? We wanna be able to give them that functional, intelligent, understanding so that it can be applied not just superficial, cool superficial. But not the superficiality of genetics. We want the functionality of genetics. Which is what we do.
Yeah, and I mean, from my understanding, what I really like about my report, which I’m gonna just pull up in a quick second, and I have a couple of things that I wanna get into, but the idea that you’re looking at things together, like not just one gene at a time, but these things are all interplaying, and I think that piece is really, that brings a whole other layer which you cannot get from some of these.
And this, by the way, Sanjeev it’s so brilliantly that you bring it up. That’s the base, that’s the foundation of functional genetics. Nothing, if we understand, which is what I just said, that our goal is the functional performance of a cell. You see, look Sanjeev, our genetic makeup defines how our cells work. Our cells behaviorally, how do our cells, How do our cells absorb the nutrients that they need? How do our cells get rid of the waste products? The toxins that they produce both internally and that they’re faced with because of our environment. How do ourselves build the proteins that we need?
The neurochemicals, the hormones, the things that we need to function at the cellular level and therefore the organelle level and therefore at the holistic level. This is the human being. And we wanna be able to read that manual and infer these awesome functionality, these things that make us who we are. Well, the moment we get to that perspective, we need to understand nothing in the human cell works as single genes doing their own thing. Rather, all of these beautiful behavioral concepts of a cell how good is the cell doing such and such? How efficient is the cell at detoxifying such and such? It relies on gene pathways. It relies on gene networks. It is the inclusivity of multiple genes each doing their important functions but doing them in a coordinated, circadian rhythmic pathway manner. And once you are able to read the pathway, once you’re able to read the interconnectivity of the genes, that’s when the magic happens, that’s what we do differently.
Yeah, I think that’s exactly, so well said. So this longevity conference, I’m particularly interested on how the DNA Company test can help guide somebody on making better decisions if they wanna improve their longevity, decrease inflammation of the body. I was looking at some of the gene markers, I’ve been looking at inflammation of the lining of the endothelial cell. I believe it’s one of the genes and I’m interested in, you know, another one, you know, is there some genes that can tell you what type of diet might be better for your body? So I don’t know if you wanna talk about those.
Absolutely, you know, Sanjeev, and this is the thing that makes your practice so amazing. And obviously being a pioneer in leading these types of conferences is that you get that. I used to think this was superficial a few years ago because I would hear it in some circles and I’ve now come full circle and realize that it’s not superficial at all. If someone wanted to ask me, Mansoor, is it even possible to use one word or one term that defines the greatest obstacle to human health? And I would say, again, I used to say, no, it’s impossible. Now I think it is possible. And I would use the word or the term chronic inflammation.
It seems like an overly superficial catch-all, but we’ve now by studying every form of human disease whether it be disease that is internally, meaning something that is not happening because of our genetic manual, by the way, efficiently, and so we’ve got this inheritance, or this predisposition to certain health outcomes or whether it be because of a challenge we might have the best genes on the face of the planet, but after all, if we’re constantly being bathed in wrong in the choice, you know, toxins, environmental, purposefully, you know, purposefully or not. Or whether it be diseases based on infections, very important in the times that we live in. A baseline, and by the way, we’re including things like cancers, and we’re including things like metabolic syndrome diseases of diabetes and so on and so forth.
That what is it is there, is it even possible that at the baseline, at the background of all of what appears to be these diversified diseases, is there a common denominator? And the answer is yes, actually there is. The concept of cellular inflammation. And so let’s dive into this very quickly. Because it will be the roots of anyone, anyone who is intelligently pursuing the concept, whether it’s clinicians for their patients or patients for themselves. And of course, as clinicians we wanna practice what we preach.
So we do it for ourselves. If we wanna practice optimal living, optimal health, with a viewpoint of longevity and not longevity here just for, you know, I wanna be 120, or I wanna be 100, but longevity that we age well and that we’re still functional at 80 at 90 or whatever age that magic number is. We’ve got to understand this concept of cellular inflammation and the capacity for it. So let’s quickly dive into this. Ultimately, Sanjeev, if you break it down, what do cells have to do? Each one of our cells, whether there’d be a retinal cell, a central neural cell, a skin cell even, the lining of the respiratory, the epithelial lining of the respiratory system, the endothelial lining of the blood vessels, or kidney cell, or liver cell, or a cardiac cell, whatever it may be, a cell, ultimately, let’s break it down. It needs to live, cells need to live. In order to do so, they need to absorb nutrients.
They need to respire, they need to absorb oxygen. They need to combust the oxygen with the nutrients that they absorbed. Create ATP or the equivalent of it for energy. So that that cell can live, bottom line. Now, when a cell does that. Depending on its function, maybe it’s a peripheral muscle cell a peripheral neural cell. Maybe it’s a kidney cell, a nephronic cell, maybe it’s a liver cell, a hepatic cell, a vascular cell, whatever it may be, that has just done its job of living. Now that it’s living, now that it’s able to take from its environment, oxygen, nutrients, respire, make ATP.
Now that cell has to do something, okay? And the things that that cell has to do might include making a slew of different proteins, that it contributes to the function of the cell. It contributes to its surrounding tissue. It makes up the organs. Okay, so cell cells have to live and then they have to contribute functions. Now, when we take these two basic concepts when cells are living and contributing by whatever job they have to do, what happens to cells? Two things, they produce as a natural byproduct of living, a natural by-product of making that ATP, they produce oxidants. And these oxidants, we have a delicate balance. And look at the beauty of this. I can see beautiful, some might consider it morbid but the very things that make us live also are the things that will slowly kill us.
By breathing and consuming, by creating ATP to live, the law of physics is we cannot create energy except we create a by-product, in this case oxidants is that byproduct. And by the way, those oxidants are the things when in surplus, because by the way, a certain amount of oxidants is necessary for cellular behavior. But in surplus, oxidants are the things that will slowly erode the functionality of a cell. So this is the first thing that we’ve gotta understand, okay? And again, very quickly, the other thing that we said is as the cell is doing this function, some cells more than others, it’s exposed to environmental toxins, because when we breathe in, we don’t just breathe in oxygen, do we? We breathe in the pollutants that are in the air, organic, inorganic, we breathe in mold toxins that might be in the air.
For example, certainly the chemical toxins that are in the air. We eat things that have preservatives pesticides on it. So the other things that cells have to do is they’ve got to have the ability, they’ve got to, cells have to recognize that they’re going to be exposed to things that are beyond that which they needed for healthy, functional living. They’re gonna be some nasties that come in. What does the set the stage for, Sanjeev? It sets the stage that cells, and obviously based on the individual their cells have differing capacities. You, me, Joe, John, Paula, Lauren, will have different capacities to do what? Two capacities that we have to look at.
The efficiency with which we energy, i.e. absorb the nutrients, take care of the mitochondrial function. So we, a, have different innate capacities to make the energy so that we can live. That’s an innate capacity. And we have different innate capacities to ward off, to deal with the oxidant toxic exposures which combined together creates a unified equation of inflammation. So here, when we summarize these two things in quick summary, we have, if the goal of longevity is to keep our cells producing energy that we can live and keep our cells doing the functions they need to do, all of the different functions as optimally as possible.
We must know that on the flip side of that equation, our cells have to accomplish two fundamental truths which are embedded much of it in their genetic code. And therefore, to answer your question, those are the things we need to go study. What are the two fundamental truths in your genetic code that the fundamentals of how efficient are you at keeping yourself doing the jobs. The mitochondrial energy producing jobs that they need to do, and how efficient are you at getting rid and handling the inflammatory byproduct of living. This creates a seesaw balance, Sanjeev. And in conclusion, the individual who has the genetic capacity for efficient energy production and efficient toxic inflammatory clearance, when their balance is in favor, that they’re always producing energy better and keeping their inflammatory load lower, this dynamicism equals optimal health.
They’re not against each other though, right? Like these are not-
They’re not against each other. No, no, no, no, no
You can have both high, you can have both low, it doesn’t.
Absolutely, and so of course, the individual who, because of their lifestyle choices of environmental exposures like nutrition choices, that for what is unique to them, genetically predetermined, if they find themselves because of their choices and because of their innate genetic capacities, that for periods of time in their life, their inflammatory load exceeds their antiinflammatory potential. So now they’re existing in a surplus of inflammation, a person that stays in that modality, that’s the person that’s walking the path for chronic disease.
That’s the person that is going down a path that is not equal to optimal longevity versus quickly, the person who their inflammatory load is in a deficit, meaning their cellular capacity, the ability to create that energy. The cure for the inflammation is a by-product, intentionally, unintentionally, innately, and that which comes in externally. If their capacity, everything is working well, they’re using the right fuel of visibly the foods they eat. Their right environment, they’re making the right lifestyle choices. They’re not exercising in a way that is exceeding their oxidant capacity. Not all exercises are created equally.
They are feeding their unique microbiome in a way that the unique microbiome is living in harmony with their body so as not to put additional strain on the body because the microbiomes, Sanjeev, is one of the primary sources of the inflammatory, potentially, primary sources of the inflammatory challenge that the human being faces from within. If such a human being has all of these things in their favor, such that their capacity exceeds the load of inflammation that they’re faced with, that’s optimal living. That’s the person who can go on having cellular function, cellular repair, cellular replacement, and living 70s and 80s and 90s and beyond.
You think that, like some amount of damage, metabolic damage, or inflammation is occurring in everyone. I mean, that’s why aging is happening.
That’s what he was saying yesterday. We all, nobody can be at zero.
Like producing it to the level that, I mean, whatever you can do to have it the minimum level possible.
So there are three factors here and you’ve nailed it again surprisingly, Sanjeev. The fact is we’re never zeroed out. The fact is our capacity, so let’s get this concept. There is a capacity, cellular innate capacity through all of these amazing mechanisms of antioxidation, detoxification, mitochondrial function, nutrients absorption, cellular membrane performance, hormonal performance, through all the summary, all of these things ourselves have the capacity to handle inflammatory load. Okay, inflammatory load. The higher the capacity to handle that inflammatory load, the more we can tolerate.
We have one person who has smoked all their lives and drunk cognac since they were 14, and here there are 80 with a cigar in their mouth. So cognac in hand, and they’re healthy than you and me put together. Okay, so we have that innate capacity to handle inflammation. And we have the inflammation that we’re exposed to. Now, the inflammation we’re exposed to is never zero because that inflammation is a necessary byproduct of our cells living, as we said earlier. So with time, there’s always a background erosion, there’s always a background diminishing of our total cellular performance, but the higher the delta the greater the delta between cellular capacity and cellular challenge, the slower is the accruement or the accrual of that erosion. Okay, so this is the first concept that we have to focus on.
The next two concepts are also as important, and that is, well, actually it can be put into one concept. And that is the state of the stem cell population in our bodies. You see, as this erosion, as our cells are during the jobs, capacity versus challenge, and they’re going along throughout our bodies, cells have two options. Well, they have three options actually. The first option is they do their jobs and there’s a half-life to the cells. So cells are doing their jobs, and of the billions and trillions of cells in our bodies, different cells have different half-lives. So skin epithelial cells have different half-lives within cardiac muscle cells or central neural cells or kidney cells or liver cells and so on and so forth. So different cells are able to do their jobs, red blood cells, you know, famously have a half-life, what is it up to Sanjeev? 40 days, what is it?
90 days, something like that.
Is that the half-life or the full life?
Half-life you’re right, maybe 40 days, yeah. Complete turnover.
About 40 days for half-life, right? And so then they did turn over. So they’re doing the jobs, hemoglobin in them taking in oxygen, transporting the oxygen to the body. And those red blood cells have a half-life. The red blood cells circulating in my body and your body right now are not the same red blood cells that were there when this pandemic began last year or October of last year, or even maybe December of last year. They’re different red blood cells. So the point is this, when our cells are facing this equation of capacity versus load, they’ve got to make, they’re doing the job, and the body has to decide, am I going to keep that cell doing its job as it starts to erode, as that cell becomes weaker and weaker at doing its job over the period of the life of that cell? Am I going to attempt to fix that cell? Am I going to attempt to repair it? Am I going to attempt, or am I just going to kill it off and replace it?
This is the second and third components of longevity. So the first is where are you on the equation of cellular capacity and cellular load in terms of inflammation, number one. How good is your body at making the decision should we keep that cell going even though it’s not running at 80% of its original you know, and capable of capacity. Now with 70% efficient at what it’s doing, now it’s 40% efficient. Okay, hold on, time for you to either be replaced or-
What are your signals? Like, what do you think? In your mind, what are the things the factors that influence how the body makes that decision? Like what could one do? Like for example, could keto or fasting make an impact here I assume potentially?
Brilliant, you know one of the first things we need to do, optimize, one of the first things, and this is something if you asked me this question a year ago, this is the great part about medicine, that we should always be evolving and trying to learn better, isn’t it? So if you ask me this question two years ago, I wouldn’t give you the answer I’m about to give you. And that is the first thing that I’m now utterly convinced that we need to do to accomplish what we just said, is optimize our hormonal systems, why? And by all hormonal systems, I mean, thyrodic function, I mean, insulin function, I mean, sex hormone function, these primary, these precedent setting hormone systems in the body, why? The answer lies, and all of this by the way Sanjeev is based on our genetics which we look at.
These are the systems that we look up at the DNA Company. What did I mean? So you asked the question of antiaging. You asked, Mansoor, now that we know we’ve got to make, we’ve got to optimize where we are on our capacity versus load scale, of course, load, inflammatory load. Everyone can address this by the decisions they’re making, right? I mean, the person who is smoking a pack of cigarettes a day is adding inflammatory load to their body way more than the person who’s not smoking.
The person who’s made a conscientious decision to eat healthy unprocessed foods, foods not leading with added sugars and food colorings. And so has made a decision to reduce the inflammatory load of what they’re putting into their bodies. Okay, so we can do that. But then we have this other thing that is hard for us to figure out, how do we help our bodies to make the better decision between replace and or repair? How do we keep the cells that we have, which are turning over at different rates, depending on the cell type. How do we keep those cells, pick a number, working at 75% efficiency? ‘Cause here’s the thing, Sanjeev, do I want in any given organ type, do I want most of my cells at 75% or more capacity? Or do I want cells still sticking around doing the job at 40% or 30%?
Right, because we want our bodies to have the ability to go, yep you dropped below 60%, off you go, put back in the new guy who’s back up to 100% or 90% as the case might be. We want this. And to do that, we need adequate stem cell populations in the body, right? Because those stem cells will give, they’re the primordial cells roaming the body either contributing cellular factors that are repair cellular factors. So stem cells reach the parts of the body. They contribute the environment to help keep those cells rejuvenated, or they flat out replace the existing cells.
So now you ask the question, Mansoor, what can you do about this? And I said, the first thing that I would say now is optimize your hormonal systems, why? Because Sanjeev the answer to this lies in, and so many clinicians, and this is what got me on this path, don’t even recognize how hormones work. How do hormones work? Hormones, any hormone, whether it be insulin, whether it be thyroid hormones, whether it be sex hormones, testosterone, progesterone, estrogens, hormones work, vitamin D i.e. the 1, 25-dihydroxycholecalciferol hormonal, which is as important and more important than most other hormone systems. Hormones work by binding to their receptors.
So for every hormone in the body, cells produce the receptor to that hormone. We have the insulin receptor for insulin, the estrogen receptor for estrogen, testosterone androgen receptor for androgens, vitamin D receptor for vitamin D and so on and so forth. Now, what is the key here? When a hormone binds to its receptor, what does it do? And I’ve asked this question and I won’t put you on the spot, because I know you get this. But I asked the number of clinicians I said, how does testosterone do what testosterone? Like how does testosterone actually androgenize the body? How does it do that? Well, it’s a hormone, it’s an androgen hormone.
And it impacts the cells by, no, no, how does it do it? Well, what do you mean, Dr. Mansoor, it’s a hormone, it gets absorbed, and it creates these chemical reactions. No, that’s not how a hormone works. A hormone works by binding its receptor. And once that receptor is bound by its ligand, it is now called an activated receptor, and this receptor with its ligand, with its hormone together, and sometimes other factors, now transposes and becomes what? A DNA transcriptional modifier. That’s what a hormone does. A hormone binds its receptor, and then creates a complex that goes into the nucleus of the cell and initiates gene expression. So after 22-
After the cell membrane actually comes-
It crosses the cell membrane.
Actually comes in, this hormone crosses over.
The hormone comes in through the external, the extracellular space, comes into the intracellular cytoplasm, wherein and hormone receptors are either on the actual outward facing cell membrane. They are sometimes in the cytoplasm and sometimes, they’re already waiting in the nucleus. So the hormone comes in from the extracellular space, having been produced 1, 25-dihydroxycholecalciferol having been activated through the liver in the kidney. So now the kidney, which is where the actual final activation of vitamin D occurs, releases 1, 25-dihydroxycholecalciferol, the hormone I hate when people call vitamin D a prohormone.
D3 is the prohormone. 1, 25-dihydroxycholecalciferol is a hormone of hormones. It trumps many of the hormones in the body. It’s a hormone, that hormone is released from the kidney into the bloodstream, carried by a hormone vitamin D transporter known as the vitamin D binding protein. It circulates in the blood. It enters into the cells, all of the cells of the body. And different cells of the body have more or less vitamin D receptors. The vitamin D will bind to the vitamin D receptor, the vitamin D receptor couples with the retinoid receptor, the RXR receptor, this vitamin D retinoid receptor, coupled with the 1, 25-dihydroxycholecalciferol, this tri-complex now enters into the nucleus and of the 22,000 odd genes that make up our operating manual, a minimum of 1/10 of this gene, we think maybe even more, but at least 1/10th of all of the instructions in your body, those genes only get turned on when this vitamin D receptor complex binds to the gene signaling to the gene epigenetically that it’s ready to be turned on, which brings me to another important point, which is my pet peeve. How many people talk about epigenetics?
Oh, well, Dr. Mansoor’s genes don’t matter, it’s the epigenetics of it. And they can’t even tell me how epigenetics works. Because by the way, the epigenetic control of 1/10th of the human genome is dependent on the binding of the vitamin D receptor complex. Each one of those things are genetically controlled. So our actual genes, the gene version of the vitamin D receptor that you have, the gene version of the vitamin D binding protein that you have, the gene version of the CYP2R1 enzyme that activates your vitamin D that you have. Each of those genome types defines an outcome.
Vitamin D, getting into the cell, binding its receptor, forming this complex, which then defines the epigenetics of 1/10th of your genome. So epigenetics and genotype are not some independent things that all the genotype isn’t important but the epigenetics is. This is complete ignorance on the part of people who try to make themselves, you know, experts in the field. Now, every single one of those hormones have their, what is called transcriptome. So we’ve got 22,000 odd genes and different subsets of genes are optimally expressed and only optimally expressed when initiated optimally by the hormone receptor complex. So if we want our genes, optimally being expressed and why do we want genes, optimally being expressed? Because the optimal expression of genes signals the optimal functionality of the cell.
So that’s why you’re saying about it’s important about body will make-
Hormone systems, there you go, right? So when you asked that question, all of that to say, if we optimize the exposure that we have, the circadian rhythm exposure we have to vitamin D, to our testosterones, and estrogens, and thyroid hormones. And we could pick the main ones and insulin. Are you reducing insulin? We want to reduce the transcriptome. And the transcriptome here refers to the portion of the genome, the X100, the X1000 genes who are under the influence of which of these hormonal systems. In the case of insulin, we want to limit how many genes i.e. the insulin transcriptome.
We wanna limit the number of times, and the duration, that the insulin transcriptome is being expressed, right? So sometimes we want to improve the transcriptome of that hormone. Other times we want to limit the transcriptome of that hormone. When this is done. Oh, no, no, and when this is done, this, Sanjeev, this Dr. Goel, when we, the, when, here meaning the if and the when, because I’m not trying to make it seem as though we’ve got some mathematical formula that says this is the exact optimal thing. But once we conceptually understand that when we optimize these transcriptomes, these rhythmic expressions and suppressions of the human genome in the right cells, at the right times, that equals optimal health. That equals optimal health.
Some things are just being tied together. So I don’t know if you’re familiar with this. It’s an epigenetic test looking at methylation of particular genes, and they have one for looking at a particular diabetes gene. And then they can tell you your risk, I guess, you know, how much methylation, which I assume might be happening by insulin, perhaps, I’m not even sure.
It’s a wonderful thing, absolutely. And so of course, what does the insulin receptor do? And there’s a brilliant brilliant study coming out of the Netherlands. And in that study, they showed that when the insulin receptor has been activated by insulin, secondary to the exposure of elevated blood glucose. So of course we eat. And by the way, it’s not just eating sugars that can do that, okay? And by the way, there are internal fat storages that when we exercise, can trigger a glycemic event. So sometimes people go, I didn’t eat. I tested my blood sugar before exercise and then I still didn’t eat. And I tested my blood sugar an hour after exercise. How the hell did my blood sugar go up on a pinprick? Well, because your body needed to generate glucose secondary or in time of your exercise. So the body has its internal limit to whatever that fatty liver and other things that you have, point is this, what these researchers so beautifully showed.
They showed that when the insulin receptor was bound by the insulin produced because of the elevation of glucose in the bloodstream, the insulin receptor transcriptome, the subtotal of all of those genes that were being expressed in relation to insulin, unsurprisingly, many of those genes were the genes required to make the enzymes for the Krebs cycle, right? Makes sense that when insulin bound its receptor and that insulin receptor complex went into the nucleus, it turned on the genes, unsurprisingly, that are needed for glucose metabolism and the Krebs cycle within the mitochondria.
That makes all the sense in the world. But when that insulin receptor insulin complex stayed activated for more than frankly short periods of time other genes under its control were exceedingly, created a pro-inflammatory outcome in the cell, such that quote, the study, and quote the amazing clinicians that had the study, they said, cellular behavior under the influence of chronic insulin receptor activation meaning cellular gene expression, secondary to prolonged insulin insulin receptor activation mimicked what a body is like when there’s a viral infection.
Oh my gosh, wow.
It literally mimic so that you start feeling flushed, you start feeling fatigued. You start having the surplus of oxidative stress. They literally study gene expression of these individuals in prolonged insulin receptor instant activation. And that gene expression looked just like if the person was going through a viral infection.
People complained like brain fog after they eat a high carb meal or something, do you think these things are, these are like related effects of effects potentially?
100%, 100% because we are transiently creating this. We are transiently secondary to the insulin receptor activation, elevating the inflammatory load within the cell. And now that inflammatory load may or may not exceed the inflammatory capacity that will each individually have. And so of course, yes, they’re completely, you know, one of my favorites food vloggers is a gentleman called Mikey Chen. So he’s one of these famous food bloggers. And, you know, he travels the world eating food, something they’ve vicariously live through. I don’t eat like he does, but the point is this, this gentleman eats more carbs.
If I were to even smell the amount of carbs that he’s eating in terms of rice and noodles and sweets and desserts I would be dead within a year. And here he is, you know, ostensibly fit as a fiddle. And he’s been doing this for several years now. In other words, his innate inflammatory capacity, secondary to the initiation of his insulinimic transcriptome, but because of his genetic, his genotype for the factors that lead to that is way beyond mine. And that gene that you’re referring to, the TCF702 Thursday Charlie Friday 702 gene is a gene that is fundamentally related to the activation of insulin sensitivity or insulin insensitivity.
There’s an A allele and a G allele, right, I believe?
Right, yep, and so at all, otherwise the C and T allele, okay? And so when you carry the T allele, which is the suboptimal version of the G allele, which I believe that we both carry, I certainly carry the T allele.
We are what? We are innately more insulin resistant.
And what happens with insulin resistance, which is a precursor? It does not mean you have type two diabetes and not all people with type two diabetes are necessarily insulin resistant. But when the you and me’s of the world, literally our insulin receptor, that very receptor that has to be activated to go into the genome. When it is less sensitive to the presence of insulin, what happens? What happens is when we eat a high carb based meal or at least a meal, whatever that meal might be, that overly elevates our postprandial sugar. Initially, our bodies do not listen to the insulin signal that is appropriate for that level of sugar.
So initially we go into a hyperglycemic mode and the hypoinsulinemic mode, but as the body continues to detect that blood sugar isn’t coming down very efficiently. Guess what it does in insulin resistance individuals, it now sends a signal to the islets of Langerhans in the pancreas, and we just start pumping up more and more insulin. We then at about the two hour, three hour mark, we now become hyperinsulinemic, our blood sugars plummet, but we’re still activating the insulin receptor after the blood sugar has come down. And we’re still telling the cells, turn on the insulin transcriptome, the insulin receptor transcriptome. And now we put our bodies in for a number of hours postprandially, our bodies are in that modality is defined by those Dutch researchers and clinicians where we are in a proinflammatory mode. All because we ate one too many croissants for breakfast.
Wow, let me just check here. Hang on, we’re gonna edit step up how our time is like. How are we doing with time?
Oh, 2:08, then you gotta go soon, right?
I’ve got because you know, I told the guys that I was running 15 minutes late, so I have about 10 minutes.
Okay, let’s try to wrap up soon. Just jumping in there. Just wanna finish this topic because what do you think, do you think that people’s response to the GLP-1 inhibitors is different for different people? ‘Cause you were saying like now, we have different responses to how insulin and this type of medication, apparently, somehow regulates how insulin is being used. And then some people have good weight loss response and some people don’t, I’m just wondering have you heard anything?
Because the pathway upon which these class of drugs work, assumes a normative responsiveness to insulin. That, of course, as we go down the type two diabetic modality, how we got there, putting that aside, we still have to come back and realize what is the innate receptivity of that receptor? And if a person is innately less receptive, i.e. innately insulin resistant, which literally means it literally means that receptor isn’t responding. Isn’t being initiated initially as efficiently. But then thereafter, there is hyperinsulin receptor activation creating chronic hyperinsulin transcriptomic expression.
We can see now that the stratification of course, essentially, if this comes right back to a fundamental of pharmacogenetics, isn’t it? That when we define therapeutic pathways, we define therapeutic prophets often in a very generic sense. And we’re not considering the individual stratification of the population that we’re about to treat. The same very quickly, Sanjeev, that can be talked about, well, if you’ve understood and if our audience understands everything that I said, we might say, well, good. This is why hormone replacement as we go into menopause or menopause is such an important thing.
And it is an important thing, maintenance of hormone levels in an intelligent way, in an intelligent way, and in a circadian appropriate way is definitely one of the things that should be in the conversation for someone looking at antiaging and longevity. However, if you didn’t know the receptiveness of your androgen receptor, if you didn’t know that you have a weak androgen binding capacity, that literally your androgen receptor is sparser it cannot handle as much testosterone. And of course, we would have seen the manifestation of this in you as a young man in your youth, where you could be slim you could be, but you’ll never have that muscle striation indicative of androgenization of the body because mind you, your receptor is just not getting activated as it should be.
It is different from the conversion. Like I know in the functional genomics panel, you look at.
This is a totally different to the receptor now
It is in addition to that, it is the receptor, and this is why I say, this is why I signal, we look at our functional pathway to tell you how much testosterone you’re making, how efficiently you’re making it. How much of your testosterone are you converting to DHT? Why do you wanna know that? Because DHT, dihydrotestosterone, binds with a greater attractiveness, with a greater, what’s the term, it’s binding capacity affinity, with a greater affinity to the androgen receptor. One molecule of DHT can outplace six molecules of testosterone. We can define all of that genetically. And then once we determine where you are in your cascade, now we ask, it comes back to the fundamental, how are you activating that androgen receptor? How are you activating that estrogen receptor?
Because to the degree that you activated the androgen receptor, the estrogen receptor, at the right time, with the right intensity, for the right duration, that is the degree to which your cells express the genes which is the only way that the testosterone is impacting your cell to the right transcriptome for the right time, for the right duration. This is where it comes back to Sanjeev. And this is where the DNA Company, this concept of the circadian timing and knowing what are your genetic predicates.
So we are becoming the first in the world. If I wanna summarize here, Sanjeev, we’re really becoming the first in the world to dovetail genotype with epigenetics. We’re actually showing how your genome type radically influences your epigenetics, think hormonal receptor activation of your genome. And it is this confluence, this coming together of a sound and intelligent knowledge of genotype with a sound and intelligent knowledge of, what is gene expression that equals optimal cellular performance? When do I want those cytokine genes expressed? When do I want these circadian genes being expressed?
Remember, Sanjeev, we had this amazing time together at a particular results of the CHS two years ago. And we were sitting there having lunch. And one of our colleagues was talking about taking magnesium threonate late in the evening and that she started not being able to sleep. And I kind of just looked at her, I said, well, why would you take magnesium threonate late in the evening, it activates BDNF. And why are you activating BDNF at 10 o’clock at night? So this knowledge in conclusion, Sanjeev, this knowledge that there is your genotype, your gene makeup, and a lot of your genotype influences your epigenetics, which then influences gene expression. Optimal health, in conclusion, is the appropriate expression of the appropriate genes at the appropriate time for the appropriate duration, that’s optimal health.
Okay, that’s awesome. Thank you so much. Mansoor, the more I talk to you more, I realize how little I know, but we keep learning more and more about the human body. I think this is an exciting time.
Indeed, this is the cool part.
And so I think just a nutshell, well, I think what I want our listeners to know is that really the test looks at, I think, what? 30 of 30 genes?
So by the way, all of these new pathways we’ve added them now, Sanjeev.
Oh, wow. I need to get update. So the test looks at all a whole bunch of these genes, and then I can help-
In a functional pathway perspective.
And so they can understand their own personalized makeups. So they can, I guess, optimize, you know, the strategies need to live, to reduce.
They can optimize their strategy. Even if we get the 5% of it then the 10%, meaning as our knowledge grows, they can optimize the goal of expressing their genes, the right genes at the right time, for the right durations, in the right cell types, at the right times in their aging cycle, for optimal health. That’s it’s of course it’s a big vision, but that’s the real, that’s where the magic happens.
Yeah, awesome, thank you so much, Mansoor. Have a great day.
It’s a pleasure, Sanjeev, same to you.