Gladden longevity — Episode #19

Speaker 1:  Welcome to The Gladden Longevity Podcast with Dr. Jeffrey Gladden, MD, FACC, Founder and CEO of Gladden Longevity. On this show we want to answer three questions for you. How good can we be? How do we make one hundred the new thirty and how do we live well beyond one hundred and twenty? We want to help you optimize your longevity, health and human performance with impactful and actionable information. Now, here's today's episode of The Gladden Longevity Podcast. The Gladden Longevity Podcast is provided for informational purposes only, it does not constitute medical advice. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The use of any information and materials linked to this podcast is at the listener's own risk.

Dr. Jeffrey Gladden:  Welcome everybody to this edition of The Gladden Longevity Podcast. I have the pleasure of being here today with Dr. Gil Blander. Dr. Blander has a PhD in biology and he is the founder of a company that's really focused on improving the health of people at home. It's called insidetracker.com, insidetracker.com. Gil, it's a pleasure to have you with us on the show today, thank you for being here.

Dr. Gil Blander:  I'm excited to be with you, Jeff, looking forward.

Dr. Jeffrey Gladden:  Yeah, great. Why don't you share with the audience a little bit about your story of how you got to be sitting here today on this podcast? What brought you to starting InsideTracker and all that sort of thing? What's your personal journey there?

Dr. Gil Blander:  Sure, as you can hear for my accent I'm not a native American. Born and raised in Israel. From a very young age I wanted to understand why do we die, how can we extend the life span, how can we prevent aging-related diseases and that's why I decided to study biology. I done my...

Dr. Jeffrey Gladden:  Okay. Let me interrupt you for a second.

Dr. Gil Blander:  Sure.

Dr. Jeffrey Gladden:  You started doing this at a young age, what prompted that? Was there something in your family or in the neighborhood? What got you thinking about longevity at a young age?

Dr. Gil Blander:  Yeah. At the age of twelve, my aunt passed away from cancer. And instead of being sad about her, I started to be sad about myself that I won't live forever. Because that was the first indication in my life that I won't live forever. And because of that, that actually raised my fascination and curiosity about aging and longevity.

Dr. Jeffrey Gladden:  Nice. Yeah, I find that true for a lot of people. It's when they come face-to-face with their own mortality that a switch flips. Whether it's about health or longevity or whatever it is. So, yeah, that's interesting it happened for you at age twelve. Good, so from there you started studying biology and then where?

Dr. Gil Blander:  Yeah, so I did my undergrad at Tel Aviv University, my PhD at the Weizmann Institute of Science. And then I decided to do my postdoctoral fellowship at MIT, at the lab of Lenny Guarente, which is one of the leader of aging research. For your audience, the longevity is in the title so I'm sure that they heard about SIR2 or the sirtuin. It's a protein or genes, that he found, that in yeast they can extend life span. And he and others showed that it can also do that in other organisms such as worms, and flies and even in mouse.

Dr. Jeffrey Gladden:  Was all the research being done on different animal models? Is that what it was or...?

Dr. Gil Blander:  Yeah, yeah, his original work was done on yeast. He screened to find the genes that extend life span in the yeast. And just for the audience, yeast, it looks for us like it's immortal when you make bread or beer. You think that you take a piece of yeast and that will live forever. But actually, if you look at a single yeast and allow it to replicate, what you see is that there is a mother cell and a daughter cell. The mother cell is much bigger, the daughter cell is much smaller. And if you isolate the mother cells, replication after replication, you can see that after around 10 replications or so, the mother cells stop dividing. And that's basically a cellular senescence of yeast. And based on that, because of this phenomena, they started to screen for genes that can extend the number of replication that the mother cells...

Dr. Jeffrey Gladden:  So if I'm understanding correctly, were the genes they were looking for, genes that would mitigate the development of cellular senescence? Is that what the angle was? Or were they looking at something else?

Dr. Gil Blander:  No, they were looking for genes that will allow yeast to live longer. Because again, if you look at the mother cell when it's [inaudible 00:05:23], yeah it's a cellular senescence of yeast, but if you look at yeast, it's a single cellular organism. So it's actually the aging of the yeast cells, yeah.

Dr. Jeffrey Gladden:  Right, right. But cellular senescence, if you were going to be looking at genes that would allow it to live longer, then it would have to push cellular senescence off into the future, I would think, right? So is that what you were seeing, that cellular senescence happened later in the yeast? Or were you looking at genes that somehow weren't directly related to senescence, but we're actually improving the quality of life so that senescence didn't happen? Or what were you actually seeing there?

Dr. Gil Blander:  Again, it wasn't my screen, it was done by the lab before I joined.

Dr. Jeffrey Gladden:  Okay, okay, okay.

Dr. Gil Blander:  And again, I don't want to call it cellular senescence because in human you can say cellular senescence. But there, if you think about it, it's an organism that have one cell. So it's very hard to say that it's a cellular senescence, basically aging of this organism. And the screen was to find genes that extend the life span of the yeast cell. They found a few candidates. One of them, maybe the most promising, was the SIR complex, that includes SIR2, SIR3, and SIR4. The only one of those proteins or genes that was conserved the evolution was SIR2. So then they say, "Okay, if it extends life span in yeast, let's look at the life span in worms." And what they actually found that yes, over expression of the SIR2 homolog in worms extends the life span, deletion makes the worms live shorter and so on.

Dr. Jeffrey Gladden:  Let me ask a question. So CO2, when we think of CO2, we think of carbon dioxide. But this gene probably has nothing to do with carbon dioxide metabolism or generation, I'm taking? Or does it, or can you explain to us what that gene does?

Dr. Gil Blander:  Yeah, it's not CO2. It's SIR2, S I R 2. So it's not CO2.

Dr. Jeffrey Gladden:  Okay. It's S I R...?

Dr. Gil Blander:  2

Dr. Jeffrey Gladden:  I R 2, SIR2?

Dr. Gil Blander:  Yeah, yeah.

Dr. Jeffrey Gladden:  Okay. Okay, got it. So it's SIR2, okay. So like a sirtuin gene then? Okay, so we're talking about...

Dr. Gil Blander:  Exactly, yes.

Dr. Jeffrey Gladden:  Okay, so we're talking about a sirtuin, okay. I missed that. Just so the audience understands sirtuins... Sirtuins are a family of proteins that are essential for longevity and we go to great lengths to try to activate sirtuins by various mechanisms. Is that where your research came in, you started studying sirtuins? Or SIR2?

Dr. Gil Blander:  Yeah. When I joined the lab, I studied the SIRT1, which the major homolog of SIR2 in human or in mice. I also looked at cellular senescence, going back to your point, and I also tried to find the substrate. Or actually... Let's talk a bit about the SIR2 family or SIR2. It's a deacetylase, basically it removes acetyl from either proteins or histones. Most interestingly, it's an NAD dependent deacetylase. In order to perform its activity, it need to have a NAD to do that. So I was trying to find a substrate for SIR2 or SIRT1 and I also looked at what is the effect of this gene on cancer or this protein on cancer? Because if you think about it, something that extend life span, usually also increase the prevalence of cancer. Because when you allow, as you discussed before, senescence is in a way a mechanism to block cancer. But if you are allowed to go longer and you delay senescence, maybe you'll have cancer. So I did some studies and looked at the effect of SIRT1 one on colorectal cancer. And very interestingly, we found that it prevents... or delay the onset of colorectal cancer. Again, in mice. We're also seeing that it interacts with a protein called beta-catenin, which is a very important oncogene in colorectal cancer. We looked at that and showed that. I also looked at the effect of a SIRT1 on skin cells, basically fibroblast and keratinocyte differentiation and aging. So that was my work at Lenny's lab, related to the SIRT1.

Dr. Jeffrey Gladden:  So just so just so the audience gets this... So everybody's familiar with NAD and how important that is and how the NAD/NADH ratio actually goes down with aging for a variety of reasons. It's not produced as much, it's consumed faster, and there's the CD38, which actually breaks down NAD. So NAD seems to be a part of the equation here. And then part of the issue with NAD being depleted is that it's not available for energy production in the mitochondria or for activation of these sirtuins because they are NAD dependent enzymes that are deacetylase. And so when they take this acetyl group, which is just a couple of carbons and some hydrogen off of a protein, then it changes that protein in a way that it becomes active or inactive, I suppose depending on the protein. So just so you understand, this is like a bunch of dominoes that are falling. You can interrupt this cycle by having genetics that interrupt with the sirtuin formation, with a lack of NAD, with other factors that go into this. It's interesting to note that when you have enough NAD and the sirtuin are working well, that what we're talking about here and what Gill was saying is that we're decreasing the incidence of cancer. And so that's very interesting.

Dr. Gil Blander:  Yeah, again, that was showed on colorectal cancer. I'm not sure that's true for all the other cancer, it's still under the research, but that's what we have seen. So that's my work at the Lenny lab at MIT, I spent five years. And then during the time there, I was exposed to a lot of startups in the domain of biotech and others. Lenny had the company, he started the company together with Cynthia Kenyon. Cynthia Kenyon, she's a leader in aging research. She found that DAF-2 and DAF-16, which is a part of the insulin pathway in C.elegans, when you mutate those protein or genes you can extend the life span by more than two times in C. Elegans, which is a worm. And together they founded a company and I had some collaboration with that company. At that time also, David Sinclair, who was a post-doc fellow as the lab started company called Sirtris. Which was focused on some small molecule similar to resveratrol. Resveratrol have been shown by David to activate the SIR2 family. And I just said that during my time at MIT, I worked on the skin and the keratinocyte differentiation. Estee Lauder, that the cosmetic company, came to us and they were excited about my work so they decided to fund my research. And I had another company that I did the partnership with. So all of that showed me that actually the biotech industry is a very interesting avenue to work in. And my assumption when I came to MIT was to finish my postdoctoral fellowship and go back to Israel and become a professor in academia. But after a few years at MIT, I realized that actually I can contribute more to humanity by starting my own company. And also it will be maybe even more interesting than being a professor in academia. So I left and...

Dr. Jeffrey Gladden:  You came to America and became an entrepreneur is what happened? Is that what you're saying?

Dr. Gil Blander:  Exactly. Yes, yes. But I realized that I needed to learn a bit about the industry. I've seen it from the academia side, but I really needed to learn it before we start one company. So I spent couple of years in a very interesting company that is basically a systems biology, computational biology company that is looking at the body of the organism as a whole, looking at all the twenty thousand genes or twenty thousand proteins. So I decided to join this company and worked there for a couple of years. And during that time I developed a model for caloric restriction, and I assume that everyone that listening to this podcast...

Dr. Jeffrey Gladden:  You developed a model for what? Sorry, what did you develop?

Dr. Gil Blander:  Caloric restriction.

Dr. Jeffrey Gladden:  Caloric restriction. Okay, a model for caloric restriction. Sure.

Dr. Gil Blander:  Yeah, caloric restriction is a regime that has been shown, in almost every model organism, to extend the life span by up to fifty percent. The intervention is pretty simple. You cut the amount of calories that you feed a specific organism by up to fifty percent, between thirty to fifty percent, and this organism lives thirty to fifty percent longer. So what I decided to do is... it was in 2007... There had been a lot of micro-array studies that look at the expression of genes in a lot of experiments that had done caloric restriction. So I compiled all of that data, ran it via a platform that we developed there and looked for a specific pathway that is modulated by caloric restriction. And I've seen, using this computation biology platform, I've seen around twenty different pathways that were modulated via caloric restriction.

Dr. Jeffrey Gladden:  Again, this was in animal models, not in human models. Is that correct?

Dr. Gil Blander:  Yes, it was data from mice and rats. Not humans.

Dr. Jeffrey Gladden:  Okay, got it.

Dr. Gil Blander:  In parallel to that, I decided to include a couple of controls. So one of them was young versus old mice and the other was the mice that David Sinclair treated with Resveratrol. I wanted to see what Resveratrol was doing to the mice, using the platform that we have at that company.

Dr. Jeffrey Gladden:  I have a question for you. Did you find that adding Resveratrol to caloric restriction was in any way additive? Did you ever look at that or no?

Dr. Gil Blander:  No, no. I compared the signature of caloric restriction to mice treated Resveratrol. So I haven't looked at that, I cannot say if it is or not. What I found is that there've been around eighteen different processes that were modulated during caloric restriction if you compare it to normal mice. But when you look at the Resveratrol treated mice and you try to overlay the Resveratrol to the caloric restriction, I've seen only that around ten percent of the processes that modulated by caloric restriction were modulated also by Resveratrol.

Dr. Jeffrey Gladden:  OK.

Dr. Gil Blander:  So that was...

Dr. Jeffrey Gladden: So ten percent... Resveratrol is, on just a pure math basis, is equal to ten percent of caloric restriction, is what you're saying? I don't know if the physiologic effect is ten percent, but in terms of genes modulated. Yeah.

Dr. Gil Blander:  Correct, or processes. That was an interesting discovery because at that time, Resveratrol was the best caloric restriction mimetic. So because of that, I said with a couple of other scientists that work with me at that company, and we said "Okay, the best mimetic of Resveratrol is ten percent. Let's say that the second best is eight percent and so on. We'll need around twenty different small molecules to basically..."

Dr. Jeffrey Gladden:  To fully mimic caloric restriction, is what you're getting at, right? If you put together the right cocktail of supplements, you might be able to mimic caloric restriction without having to fast. I think that's what you're saying.

Dr. Gil Blander:  Correct, yes. That was the idea of the experiment. We need twenty, but we don't know which are those twenty and to use small molecules, in our opinion, wasn't the best solution. So maybe instead of that, let's use the food as a drug of choice. Let's move our drug cabinet from the bathroom to the refrigerator. We have eight thousand different kind of foods. Let's try to feed the right food for the right person. And by that, allow them to live longer, better life. But then we said...

Dr. Jeffrey Gladden:  That's an interesting shift, right? Because when we think about supplements being active, we know that food is information. We know that food will be active in similar ways. And yet, when people are eating a diet and they're getting some good things, some bad things, it's hard to know what the balance is, counterbalancing things. Some things that are pushing aging, some things are resisting aging. So I'm fascinated by this, that you were trying to nail down which foods, particularly for an individual, could mimic caloric fasting. That's almost what I'm hearing here. Is that, is that what you're saying?

Dr. Gil Blander:  Yes, yes. Not literally caloric fasting, the idea was how can we optimize our body? Because our body is a very complex machine. Because it's a complex machine, my body and your body might have a completely different challenge right now. But it's very hard to know what are the challenges that you have, or I have just by looking at me or you. It's much better to look inside our body to take a picture from the inside and understand what are the issue that we have. And then let's fix those issue with simple and natural interventions such as food. That was the idea.

Dr. Jeffrey Gladden:  Okay, now that's a beautiful idea. I've looked at your testing. It's good, solid testing. Obviously it's not super in-depth because it can't be because you're doing something over the internet. But it's certainly helpful, there's no doubt about that. So I'm really curious how you put those pieces together, based on the test results, what foods you found to be the most helpful. Maybe you can run us through some scenarios around that.

Dr. Gil Blander:  Yeah, yeah, sure. So maybe if we'll just continue the story for a second. We said, okay, we need to understand what's happening inside the body. So somehow we need to take picture from the inside. So how can we do that? And very easily and fast, we zoomed into blood biomarkers. Because blood validate and calibrate everything. You have a wealth of information about blood. We have more than one hundred year history of researching blood biomarkers and what does it mean for humans. And the peer review scientific publication is very rich about that. Also, physicians like you are using blood biomarkers in order to make medical decisions. So it's literally the gold standard, the best that we can do. But when we look at Quest Diagnostic catalog, Quest Diagnostic is the biggest diagnostic company in the U.S., we have seen that they have four thousand different blood biomarkers that they're testing. And very easily we realized that it will be super expensive to test all of them and also we won't have enough blood in our vein to test all the four thousand. So we started to look into this catalog and pinpoint the blood biomarkers that are most important for health and longevity and not for sickness. So you, as a physician, you look at a lot of biomarkers that are related to sickness. For example, PSA is a marker of prostate cancer. That's not something that we wanted to test because we are looking more on wellness and health and performance, not on disease. Based on that, we came with a battery of forty-five or so blood biomarkers that are related to age, longevity and performance. And you asked for a few examples, So we are looking at the biomarker related to lipids or lipids value. We're looking at biomarkers that are related to glucose metabolism, which is energy, which is very important. We're looking at the blood biomarker related to inflammation, related to iron metabolism, some hormone such as the testosterone and cortisol, which is the stress hormone, vitamin D, which... Sorry, yeah.

Dr. Jeffrey Gladden:  Yeah. So, here's my question. So, you go through and you test these forty-five different markers, then have you been able to do research that shows that if you eat certain foods that you actually change, not only the markers, but you change the underlying genetic expression related to those markers? Have you had a chance to do that work? I'm building from the work you did in your PhD and post-doc. Is there a connection across all of that, where you've been able to link that together? Where if you're eating parsley, your NAD levels go up and your Sirtuins are more activated and that kind of thing. Is that the stuff we're talking about or are you looking primarily at whether the biomarker shift if somebody eats fewer potato chips or more broccoli?

Dr. Gil Blander:  Yeah. I feel that it's a very good question. As a scientist, and actually we have a lot of scientists in the company, we took the scientific way. The scientific way is to look at the peer review scientific publication and see what intervention have been shown significantly to improve or to deteriorate a specific blood biomarker. In my opinion, if you look at the data about NAD and Sirtuins, for example, there is not enough information for me to come and tell you, "take NAD and you live longer." There is some data from a model organism, but the data in human is a pretty sparse and not strong enough for me to tell you or your audience to do that. What we are doing, let's take a glucose for example. If you do a search on PubMed, PubMed is like the Google of the scientific publication, and look up glucose. You might have millions of different publication about that. Then you can start looking at that and see, first of all, what is the optimal level of glucose? So let's talk about that for a second. So if you, as a physician, if you look at glucose, everyone should be between sixty-five to ninety-nine. That's the normal range. Doesn't matter if you are young or, athletic, active, or couch potato, whether you are a Caucasian or Black. All of us, have the same level of glucose, which is a normal, why? Because if you go to Quest Diagnostic again and ask them, how did you develop the range for a fasting blood glucose? They will tell you, yes, we took ten thousand people. All the people that tested with us, a lot of them are sick, because usually as a physician the people that are testing are sick. Then we found the mean, and we looked at two standard aviation above and below, and that's how we found in sixty-five to ninety-nine. But is it right? I don't think that is right. So what we have done, we looked at the data and basically we calculated what is the optimal range for which person based on their age and gender and ethnicity and athletic activity. How have we done it, first, looking at peer review scientific publication that show what is the optimal range for someone in young age in order to reach longevity? So in this example, there is a study that was done by Framingham Heart Study. Framingham is a small town next to Boston. They have around fifty thousand people and the scientific community followed this population for the last, maybe fifty years. You can look at the level of those people of glucose for a young age and see what happened to them when they died. Is there a correlation between, let's say, lower blood glucose in young age and the longevity that those people reach when they died. And there is data that showed that actually, yes, when you have glucose of around eighty at the age of forty, you have a better chance to live longer than if you have glucose of ninety at the age of forty. So based on that, we develop optimal ranges for each blood biomarker. So now it's not only normal, it's also optimal. Then, if you are out of optimal for each marker, looking at the peer review scientific publication, we can give you a recommendation. For example, for high blood glucose, the most important determinant is the amount of fiber that you consume because fiber attenuate the peaks and also allow you to absorb the glucose better. We can then come and tell you "Hey, raspberry is a pretty potent fiber machine because it has in one hundred gram, eight grams of fiber. So eat more raspberry."

Dr. Jeffrey Gladden:  We're talking about raspberry here having high fiber, which is mitigating the absorption rate of the glucose that's in the raspberry. Just so I'm hearing you properly...

Dr. Gil Blander:  Not only of the raspberry, but also on the other food that you eat.

Dr. Jeffrey Gladden:  Yes, yes. Just so the audience is clear that we're talking about the fiber actually slowing the rate of absorption of the glucose. So somebody's going to have a certain amount of sugar, let's say a banana has a certain amount of sugar, but if it's a green banana, it has more fiber. And it's not just that it has less sugar but it's that the sugar that's in it is being absorbed more slowly. Right? Just to make that point, yes?

Dr. Gil Blander:  Yes, so that's one example of intervention that you can do based on the food. Now, there are a lot of different intervention that you can do in order to try to optimize your glucose. Some of them are nutritional, as I discussed before, some of them are lifestyle. There is a lot of literature that showed that if you don't sleep well, your fasting glucose tend to go higher. If you are stressed, your fasting glucose tend to get higher. If you are not exercising, your fasting glucose tend to be higher. If you your BMI is higher, your fasting glucose tend to be higher. So based on all of that, we can look at the person, we are asking the person to enter his information. And based on all the data from the peer review scientific publication, we can fit for you the best intervention for glucose. But now we are looking at a forty-five blood biomarkers, so we can look at you holistically. Not only on glucose, but also on your LDL cholesterol, your hsCRP, which is a marker of inflammation, your iron level, and your vitamin D level and then try to find, I'm calling it the super food for you, but real super food. The food that can help you to optimize most of those issues at once. Then suddenly you get into personalized nutrition, because we are looking at all the issues that we have and find the combination that will give you the higher value for your buck.

Dr. Jeffrey Gladden:  Right. Yeah, that's an interesting approach. Obviously, there's an algorithm running in the background here, that's matching up foods to different patterns of biomarkers, right? Some of the things are difficult to get in food. For example, vitamin D is difficult to get from food. So you probably have some supplement recommendations and some things like that as well, I would think. And then sometimes if you want a lot of iron or you need more iron, that can be problematic too. If there are other issues you're trying to deal with like cholesterol, with red meat and some things like that. Somehow, you've got an algorithm that you're doing the best you can, to recommend a balance of foods that will optimize the markers. I guess, the proof is in the pudding here. How is that working out when people follow the recommended regimen. I'm sure you see improvement. Can you talk about that a little bit?

Dr. Gil Blander:  Yeah, definitely. Because we are scientists, again, we like to receive all the recommendation from peer review scientific publication, but also publish our data. So we published a paper in 2018 on a cohort of one thousand users of InsideTracker that basically got a baseline testing then, on a time span of an average of seven months, tested again. In this study, what we have done is take a sub-population of that population and looked at a sub-population that started with high LDL, or started with high glucose, or low vitamin D and so on, so forth. And looked at the effect of the InsideTracker platform from baseline to follow up. Now, this cohort of one thousand people selected five hundred and twenty-five different intervention. So on average, each intervention was selected only by two people, meaning that it's really personal. Think about it five hundred and twenty five different intervention for a cohort of one thousand people. But when we look at a specific sub-population that started with high LDL, we've seen a statistical significantly and also medically significantly decrease in the LDL. The same for the glucose, the same for increasing the vitamin D and so on. Again, it's an observational study, so I cannot say that there is a cause and effect. But, at least from the data that we see, there is a strong correlation between using the InsideTracker platform and receiving personal nutrition and improvement of those blood biomarkers.

Dr. Jeffrey Gladden:  Right, got it. That's great because I think that anything that you can do with food to help optimize your health is a step in the right direction. In this whole longevity, health optimization space, I think there's a continuum between not developing disease and then actually optimizing performance, if you will. Right? And it sounds with the changes that you're noticing, that it would have an impact certainly on disease development, is what I'm hearing, right.? Which obviously, then pushes you more into better life, longevity and health and things like that. And do you have plans to refine this model further? Are you looking at adding any more biomarkers or is there AI running in the background? What's next on the horizon for you?

Dr. Gil Blander:  Yeah, definitely. We are doing both. So definitely we are running AI in the background and one of AI product that we have is called InnerAge. Basically, we are looking at those blood biomarkers and specifically zooming in on blood biomarkers that either increase or decrease during the aging process and trying to fit you, based on your age and gender, where are you standing compared to the mean? And then if, for example, glucose is increasing during aging, if you are above the glucose for your age that means that you are older for your age for glucose, if you're below...

Dr. Jeffrey Gladden:  Let me just interrupt you for a moment. We have a lot of people in our world that don't relate to their chronological age and they don't want to be normal for their chronological age. They don't even want to be good for their chronological age. They want be compared to a thirty year old or a twenty-five year old or a thirty-five year or something like that. In the reporting that you do, is it possible to see where you stand relative to a younger age, chronological age?

Dr. Gil Blander:  Yeah. The way that we calculate it is we start with your age and seeing whether for glucose, you are younger or older, whether for LDL cholesterol you are younger or older and so on. And then we also quantify it and say for glucose, you are one year younger, for LDL you are one year younger and so on. And then we are compiling all of that together and saying your chronological age is fifty, but your biological age or inner age is forty. So then you know exactly how old you are comparing to your chronological age. Yes. We're doing that.

Dr. Jeffrey Gladden:  Yeah. Okay. Yeah, I think it's always good to hedge that by saying that this is one way to look at biological age, right? I mean, we have many different ways to look at age. We're all a mosaic of ages is the way I look at it. Between cardiovascular age and blood vessel age, and brain age, epigenetic ages, telomeric ages, et cetera. I think it's just important to understand that this isn't the be all, it can't be the be all and end all in terms of defining your physiologic age but... I see you nodding your head, yes. But, just so the audience understands, this is a way to start to get a handle on it for yourself and to be able to do it at home. Just to understand what you're getting and what you're not getting so to speak. Yeah.

Dr. Gil Blander:  Yeah. Yeah, I absolutely agree with you. There are a lot of ways to try to understand whether you are younger or older than your age. I think that what is interesting about the InnerAge that we build that others don't have, is first that it's not a black box. So everything else that you described the epigenetic age, the telomere age is a black box. There is algorithm that decided, and you don't know what does it mean? So it's very hard. So my epigenetic age is, I don't know, sixty and I'm fifty, why? I don't know why. Because there is a methylation in a specific location, even a lot of location they're doing it, they don't explain why. What is nice here is that we're coming and telling you, yeah, you are older or younger because your glucose is too high and your LDL is too low and so on. And then we are also telling you, what is the effect of the glucose or the LDL on your age. And then we are giving you some recommendation of intervention that you can do in order to optimize those markers. So in a way, we are telling you that you have a problem, or you don't have a problem. We are telling you why you have the problem, basically what marker is the problem. And then we are giving you some recommendation for intervention. What should you do in order to improve it? And none of the other thing that you mentioned before can do that because it's a black box.

Dr. Jeffrey Gladden:  Well, interestingly enough, there is a relationship between DNA, methylation, age, and lifestyle choices. And so what, we find, is that when people do sleep better, exercise better, eat better, get their body composition better not only does their methylation age drop, but their rate of aging changes. This is the Dune and Pace data that's done out of Duke, if you will. And so it would be interesting to correlate the changes that you see in the metrics that you're measuring with some other metrics. Is what we're doing actually impacting methylation age? Is it actually lowering it? Understanding that all of these markers have some ambiguity to them, but nonetheless, are we having even a bigger impact than just on the markers that we're measuring per se. That might be quite interesting to look at.

Dr. Gil Blander:  So, yeah. The current epigenetic or methylation age is not lifestyle responsive. The responsiveness for lifestyle is very, very minor. It can, maybe, if you look at that, it can change 0.1 a year, or something like that. It's very, very minor. And the reason for that is that those clocks were developed based on trying to fit the age. And they haven't been developed on a loci or location that are responsive for diet or responsive to exercise or responsive to other lifestyle event. So I...

Dr. Jeffrey Gladden:  I think you're right. The original class were basically trying to predict chronological age, but subsequent clocks are actually now looking at predicting longevity and other things. And so they do have a different metric on that. Anyway, in our work we've seen that they've been impacted by lifestyle changes just when we go ahead and measure them. So...

Dr. Gil Blander:  Okay, I would love to see it because I haven't seen a clock of today or any...

Dr. Jeffrey Gladden:  We can share.

Dr. Gil Blander:  I would love to see it.

Dr. Jeffrey Gladden:  Yeah, I can share it with you. I can share it with you. Yeah, be happy to do that. Nonetheless, I think it is interesting that the interventions that you're having with food very well may have a larger impact across more metrics that can be measured than just the ones that you are measuring. `Which, over time, would lend even more credence to what it is you're doing. Kind of a ripple effect throughout the biology. And that will probably come online as testing gets better and more data is accumulated, and there's less ambiguity about some of the other metrics. I think that's an interesting possibility. What would you like for the audience to understand about how this fits into their own strategy around health optimization and longevity, InsideTracker? How do you see that fitting for them? Maybe you can speak to that a little bit.

Dr. Gil Blander:  I like the eighty, twenty rule. If you want to get to the eighty percent, you don't need personalized nutrition and the sophistication InsideTracker to do that. It's pretty easy and there is a lot of information about don't eat food that is industrial food, sleep better, de-stress, exercise, and lose weight. That's the eighty percent. If you want to be optimal and really life longer, or you strive to live one hundred, then you need to use something like InsideTracker that will give you the twenty percent edge that nobody else can give you. So you look into your body and you understand exactly what is happening inside the body. It's very similar to what we are doing to our cars. We're taking them to the technician and they plug a computer into the car and it's telling the technician exactly what to do. That's InsideTracker. You go to the phlebotomist, you plug a needle into your vein, extract some blood and based on that, telling you exactly what are the issues that you have. And then giving your recommendation how to arrange your nutrition, how should you feed your body, how should you supplement your body, how should you exercise and how should you change your lifestyle in order to optimize yourself? So it's a matter of, do you see yourself as a Toyota Corolla or as a Ferrari? If you are a Ferrari come and do InsideTracker, if you are Toyota Corolla, you don't need InsideTracker. Just follow the few steps that I told you before and you will be okay, but again, you most likely won't get the edge that you'll receive if you're doing InsideTracker.

Dr. Jeffrey Gladden:  Yeah, I agree with that approach completely. The question I would have is how is that information communicated to the client once they do InsideTracker. They get a report, they get a call from a health coach, they get follow up testing every month, three months, six months? What's the program look like? What's the programmatic element of this? They get a dietary recommendation or recipes? What actually happens?

Dr. Gil Blander:  Yeah. So, we developed a web and mobile app. Basically, you'll receive all the results, first you will see which of your biomarkers are not optimized. Then based on that, for which biomarker, for which group, we'll tell you what are the intervention that you need to do in order to optimize and you can select the intervention. Then you can build an action plan, you can select which biomarkers are interesting for you or which goal you have. Do you want to sleep better? Do you want to de-stress? Do you want to try to live longer? And based on that, we'll receive an action plan of around 5 to 10 intervention that you should do. Then you can check-in and receive a notification and reminders about what you should do. We also recently integrated the data from DNA and data from fitness tracker. So the data from fitness tracker, for example, we can follow your sleep if you have Garmin or Fitbit, we can give you tips every day about how was your sleep and what is the best intervention for you to improve the sleep for the next night. Again, if you have Apple watch or Garmin or a Fitbit, we are also looking at resting heart rate? And we will help you to optimize that. So basically it's an holistic plan that help you to optimize your body. And we are adding, you asked before, we're adding more and more blood biomarkers. Currently we're working on ApoB, which is a marker of lipids that is somehow underrated, and most of the physician are not testing [inaudible 00:44:51] . It's a very important marker, additional marker on top of LDL to understand your lipid levels and the issues and risk. So we are adding that right now. We are working on adding more physiological marker, such as VO2 max and the HRV. So we are adding more and more marker and more and more DNA markers to allow you to understand your body better and get the edge and hopefully optimize your body and hopefully live better, longer.

Dr. Jeffrey Gladden:  How are you getting the VO2? I understand how you're getting the HRV, heart rate variability, that's picked up by Oura ring, WHOOP, lots of different things can do that reasonably well. How are you getting your VO2?

Dr. Gil Blander:  Yeah, the VO2 max is received the same from the fitness tracker. So both Garmin, and Apple watch calculate it. Again, it's not one hundred percent accurate as if you do it in the lab, but it's better than nothing. So the VO2 is coming from the data from the fitness trackers.