Gladden longevity — Episode #56

Steve Reiter: Welcome to the Age Hackers Podcast with Dr. Jeffrey Gladden, MD, FACC, founder and CEO of Gladden Longevity. On this show, we want to help you optimize your longevity, health, and human performance with impactful and actionable information by answering three questions: How good can we be? How do we make 100 the new 30? And how do we live well beyond 120?

I'm Steve Reite and, Dr. Gladden, we just got done with an amazing conversation with John Catanzaro. Is that how we pronounce it? Catanzaro?

Dr. Jeffrey Gladden: Catanzaro. John Catanzaro.

Steve Reiter: From Neo7Bioscience. And they are doing some crazy ass stuff with cancer, and you're partnering with them on some longevity stuff and disease prevention. Talk a little bit more. This was like drinking from a fire hose for me.

Dr. Jeffrey Gladden: Right. Was it? Okay, good. Because it was a lot of information coming, but super interesting stuff. I think this is one of the most forward-looking podcasts that we've ever done in terms of actually showing you looking behind the curtain. So, if you want to see what's really behind the curtain on longevity science, this is the podcast you want to listen to because we're pulling back the curtain on how we're actually decoding aging, how we're actually measuring metrics of aging that we've never had access to before by using transcriptomics and proteomics.

And then actually being able to devise solutions for what we find based not only on lifestyle and supplements and things like that, but also by building out custom peptide protocols, not the ones that you get through your pharmacy or maybe online, but these are custom-built for the individual to actually go in and modulate DNA expression, so that your DNA is actually being expressed more like a young person or as a younger person. And I'm telling you, not only does it work in the disease space, but if you categorize aging as a disease, it's working in this space too. And this is what the LIFE-RAFT protocol is about, that Gladden Longevity is running. This has been a great collaboration, and I'm super excited to share John Catanzaro and Neo7 with our community. I think you're going to love this podcast.

Steve Reiter: But we also talked a great deal about cancer, and so people that have friends that are going through cancer treatment-

Dr. Jeffrey Gladden: We did.

Steve Reiter: ... or potentially, a big chunk of these breakthroughs are seeing some amazing results.

Dr. Jeffrey Gladden: You're going to find out that there are some really effective alternative therapies for cancer here. And so, we start the podcast there because that's John's background. That's what he got into, originally. But it also builds the case for what can be done in cancer, and then we transition into longevity. But if you are dealing with cancer or have somebody dealing with it, you're going to get some really great information here and some real encouragement from what it is we're talking about.

Welcome, everybody, to this edition of the Gladden Longevity Podcast. I am incredibly excited to share with you a colleague of mine, John Catanzaro, who's the CEO and, I believe, founder of a company called Neo7Bioscience, which has been doing some really, really interesting work in the oncology space, the cancer space with regards to decoding cancer and coming up with novel treatments for cancer. John and I met a couple of years ago and subsequently have formed a collaboration that's focused on taking the same technology that they're using to decode cancer, to decode the aging process. And we'll share with you how they go about that, how we're going about that, and why we're excited about it. So, John, welcome to the show.

John Catanzaro: Thank you, Jeff. It's great being here. Thank you so much.

Dr. Jeffrey Gladden: Maybe, John, for the audience, you could give them a little bit of your background in terms of how Neo7 got founded and started and what your mission is. Maybe that would be helpful for starters.

John Catanzaro: Absolutely. It all started, of course, with my medical training in 25 years of clinical practice and going into integrative type medicine with an arsenal that, as you know, grows as you practice. And so, what winds up happening is it challenged from the very first day that patients were coming in with very resistant disease, cancer, primarily, and very difficult-to-treat and very limited treatment availability. Most patients actually were failing conventional treatments, so they were coming to us for solutions. So anyway, that challenged myself and my other physicians to work hard to figure out what else we could offer that would be promising to these patients.

And so, from there, we developed a process by which we isolated the patient's own protein peptide fragments, and then we actually began to get in more sophistication and typing. And so, I developed a team with a Dana-Farber collaboration, and then we wind up coming up with a whole platform from 2001 to 2014, working with over 500 patients with resistant cancer.

Dr. Jeffrey Gladden: Let me interrupt you for a second. We're talking about the protein and peptide characterization of a patient. I think most people understand that in your blood, of course, you have proteins that are circulating; in your cells, you have proteins that are either structural or actually function like little machines, quite honestly, doing work inside the cell, and they function like receptors and messengers, and proteins do a lot of different things. But there are certain protein signatures to different kinds of cells, and that's a function of what DNA or what genes from the DNA are actually turned on. So, if those genes are upregulated, then messenger RNA is made, which is the RNA portion, and then proteins are made.

And so, an individual's protein signature, if you will, will be different based on the state of their age or the state of their health, if they have cancer, they don't have cancer, if they have heart disease, they don't have heart disease, things like that. John, you're talking a little bit about being able to characterize these; we'll call these ‘protein patterns’ or ‘signatures’, relative to cancer. Is that correct?

John Catanzaro: That's right. And proteins actually have a 20-hour signature in the body, that most of these proteins have a half-life of about 20 hours or so. And in order for you to actually realize that that remodeling is constantly taking place in our body with these, like you said, Jeff, these protein-to-protein interactive signals, and cancer has a lot of dysfunctional disturbed signaling, and you can catch these signals and signal disturbances and capture them by doing what we call in ‘an intensive analysis’ that we do at Neo7Bioscience to capture all of those patient data points.

Dr. Jeffrey Gladden: So, really, if somebody has a malignancy, then what you're doing is you're collecting their urine for 24 hours, I believe, as well as a blood sample. And then you're actually characterizing the protein signatures and patterns inside the urine to give you insight into what exactly is the metabolic activity of cancer or the weak points or the strong points of cancer. Tell us a little bit more about what you actually learned from that protein.

John Catanzaro: In order to characterize a gene protein pathway that's involved in a disease process, then it requires us to capture all of that signature from the patient's blood and the urine, and in some cases, tumor tissue or sample tissue. And then what we do is we build what we call ‘multiplex library’ that actually puts this molecular bio-data together, and then we actually run it through what we call our ‘pipeline technology’. And the pipeline technology, then, is a very complex algorithmic engineering platform that is set to give what we call a ‘high confidence mapping, ranking and selection’ of what faulty signal pathways are demonstrated in gene protein relationships.

Dr. Jeffrey Gladden: Okay. So, this is a really critical point. So, you can actually look at these proteins and then prioritize them into proteins that are having the biggest impact on the patient's health, or the biggest impact in terms of the cancer's ability to proliferate or divide or metastasize or other things. Is that what we're saying here?

John Catanzaro: That's right. That's right. And you say it very well because the thing is that's a very complex process that thanks God for our developments with AI and machine learning and deep learning. We're able to really make sense out of a very large set of data sets that would actually be totally non-sensible if you would've just been trying to figure it out and just cut-

Dr. Jeffrey Gladden: Just looking at it. So, you've been involved with machine learning, deep learning, and now AI. How long have you been engaged with those processes? I've been aware of those processes for about the last seven or eight years when they were first starting to come online. Is that parallel to what you've been doing?

John Catanzaro: Well, I actually got involved with it back in 2001 when it was first developing a primary field of interest in bioinformatics and biocomputation. I had the privilege of working with some pretty smart people, which allowed us to enhance our abilities. So, where we've come from, the first generation development, to now where we're in the third generation development is quite amazing. Because now we actually have a completely autonomous platform which is actually, it deletes the manual steps. You know what I mean? And the accuracy is higher.

Dr. Jeffrey Gladden: So, what you're saying is that once you collect this raw information, the urine and the blood, and the analysis is done, then really it's the platform that's now doing the work of sorting, prioritizing, highlighting, all these things have been programmed, and it knows what to look for, and so it's an automated process at this point.

John Catanzaro: That's right. And it's constantly being, the engineering is consistent, so we constantly engineer and constantly revise, update, but there's so much information that's coming out on a daily basis that we're able to capture those changes and revisions, and we make those upgrades to the platform.

Dr. Jeffrey Gladden: So, you're capturing medical literature that comes into you, as well as, I assume, mining the data that you're accumulating on the corpus of all the tests that you've performed. So, is it both those elements?

John Catanzaro: Yes, it's both.

Dr. Jeffrey Gladden: Okay. That's incredibly cool. So then, what would that lead to for a cancer patient? What therapies do you then devise for them, and how do you go about doing that?

John Catanzaro: Exactly. I was mentioning that to Steve. It's like the technology advancements are incredible to where now, as you know, Jeff, the main thrust of the diagnostic world is to actually tell you what the problem is, but then they don't really lead you to the solution.

Dr. Jeffrey Gladden: Yeah, that's it. That's it. They tell you the problem, but they don't actually fully characterize the problem. So, you're just left with some very blunt tools like chemo and radiation and surgery. They're very crude tools. In many ways, they're not very selective or very precise.

John Catanzaro: Yes, correct. And so, what we've done is we've taken this precision technology engineering ability, and we've actually turned it into a solution-driven molecular design platform. That's why we say that Neo7Bioscience is a precision molecular solution company because what we're doing is we're turning these complexities found in disease pathways into viable treatment solutions that a patient can actually have a significant opportunity to take advantage of. Our primary focus is, we called it peptides earlier on when we were talking, peptides, polypeptides, when we talk about these relationships, these elements are the ground substance, if you will, of protein programming.

So, really, polypeptide engineering is actually a polypeptide programming interface that actually engineers against the faulty signal pathways that we find in the disease process. So, we're creating what we call ‘edits’, we're creating what we call ‘micro edits’ to change the bad signals basically.

Dr. Jeffrey Gladden: This is really fascinating. I think many people in the audience have probably heard about peptides. They're basically amino acids. Typically, a peptide is between two and 50 amino acids. A polypeptide, I think, would be 50 to 100, and then a protein is over 100. But these peptides and polypeptides, they signal in our body now. For example, insulin is a peptide that signals lots of things in the body. And then there are peptides that we use to heal people, like BPC-157 and GHK-Cu, and things like that. So, these peptides, the way I like to describe them is that they're signaling molecules that instead of in the pharma approach you develop a molecule that goes in and blocks a metabolic pathway, and then you hope to stop a downstream effect by blocking that metabolic pathway.

But then, of course, the molecules have to go someplace else that wouldn’t normally go into that pathway. So, then you're left with different side effects and things like that. Whereas a peptide actually sets off a cascade of events that can help heal you. So, it's information, really. But in this particular case, we're now using peptides and polypeptides to actually reprogram the cancer cell's DNA, so that it's expressed differently, if I'm understanding this correctly.

John Catanzaro: Yes, correct. It's like a very fascinating process because the polypeptides, especially when they're matched to the patient's own what they call ‘immunophenotype expression’, which we talk about the HLA matching and the HLA compatibility, these are all important because this actually aligns the programming of the polypeptides to the patient. And in a very sophisticated process, again, to get into a real alignment so that the patients, the coordinated events like you just actually mentioned, because once you start putting polypeptides into the system that are direct programming elements, then you can change a lot of different signal pathways all at once.

Dr. Jeffrey Gladden: And so, this is an opportunity to basically modulate the way cancer cells are expressing their DNA. Now, does this actually cause the DNA of the cancer cell to be modified in a way where the gene is actually modified, or the proteins actually instructing the replication of the DNA to occur in a different way to where the malignant cell becomes less malignant? Or are the peptides just blocking the expression or modulating the expression of, we'll call it ‘malignant genes’?

John Catanzaro: What they're doing is they're augmenting the expression, and they augment the expression into a forward relationship that favors the recovery of out of the disease process, right? Recovery from the disease and breaking the resistance seen in the disease, commonly. A lot of the time, what you find in a lot of disease processes, as you know, is a strong resistance pattern. And if you can actually create that real secret code to get in there to break that resistance, you're actually really influencing to more towards the recovery from the disease and more into longevity. I think that a lot of the time that if you actually, first of all, you're revealing hidden things that you wouldn't normally see.

So, you're revealing all these hidden complex interactions, and you're creating a real specific solution driven to hit those interactions that are not good. And what winds up happening is that the cells, as they have a healthy message, because it's incorporated into a specific coding forward, then the DNA actually will then express itself in a healthy manner in the progeny, in the cells that come after it.

Dr. Jeffrey Gladden: So, you're actually coaching cancer cells to become non-cancer cells, is what we're saying here, am I capturing that?

John Catanzaro: And also encouraging the apoptosis of the cancer cells that are present.

Dr. Jeffrey Gladden: Right. Because cancer cells are resistant to apoptosis. Apoptosis is a cell suicide that cells undergo, or self-killing if you will, which is how the body gets rid of malignant cells. It does that by natural killer cells in the immune system killing these cells, or the cells themselves can undergo apoptosis. But one of the things about cancer cells is they're very resistant to apoptosis. Just like senescent cells are very resistant to apoptosis because they want to stay around. They're like the ultimate survival mechanism. The ultimate evolutionary process goes on in a cancer cell to stay alive. In fact, when you think about cancer, if you have cancer, you really have a thousand cancers because there's so many different genetic configurations within that one tumor.

And so, with what you're doing here, do you actually have the ability to go into that thousand cancers within a cancer and get most of them or all of them to actually program themselves into either self-death or becoming healthier? Or how does that work? So, how do you deal with the complexity of that?

John Catanzaro: See, now, for complexity like that, where you'll actually have; we actually have patients that are in the program, their doctors put them into the program that actually has two or three different types of cancers on board. We discover the interactive coding faults. And a lot of the times, decoding pathways, as you're mentioning, Jeff, can actually be similar in a number of cancers. Cancer is not a single disease, and it's a multiplicity of diseases.

Dr. Jeffrey Gladden: That's right.

John Catanzaro: Right. And the thing is that, yes, you can have a definitive diagnosis, but really does it become definitive after you really look at the molecular data expression? Because we had one case where we saw that it was a viral-driven issue that fed the, and it's not an uncommon discovery, or you can have some adverse environmental hit that happens and that changes the whole molecular pattern. And then you say, ‘okay, well, this is common to a lot of cancers’, not just common to one type of cancer.

Dr. Jeffrey Gladden: Right. So, does that get you using things like antivirals or detox protocols or things like that in conjunction with anything else?

John Catanzaro: Yes. You can combine your treatment strategies and put them into the rotation intelligently that way. Absolutely.

Dr. Jeffrey Gladden: So, what does treatment look like? Let's say somebody has cancer, and let me just ask you this: can you deal with all kinds of cancers, solid, brain, blood, leukemia, lymphomas, and skin cancers? All those things are fair game for Neo7Bioscience?

John Catanzaro: Yeah. We're seeing them all. We're seeing all cancer types.

Dr. Jeffrey Gladden: Okay. And so, what does the treatment look like? So, somebody gives a sample of their tumor, a biopsy sample plus their blood, plus their urine. You decode the situation, and then you construct the peptides that are going to go in and modulate things. And then that's given over a year's period of time, I think. Just walk us through what's that look like for an individual?

John Catanzaro: After the analysis is done, it usually takes about four to five weeks on average. Then we actually build the analytic report and then the construct of what we call a peptide manufacturing requirement. And the end product is actually a pooled peptide product specifically designed and aligned to the patient's molecular fault patterns. And they wind up getting those in four to five treatment courses over a year. And one treatment course lasts between 21 and 30 days. And they're injected with those peptides in a combination intravenously and intramuscularly. And they can be combined with other treatments. Some doctors like to put what they call exosomal type of cell structures in there, like MSCs, they'll mix it together.

Some docs are layering on different strategies like insulin potentiating chemo strategies, or they'll do IV vitamin C strategies. There are a lot of different things that can be combined with this process.

Dr. Jeffrey Gladden: Let's just talk about some of that for a second. So exosomes, and MSCs, so exosomes are essentially packets of information that typically originate from cells. I equate them to being like letters that cells send between each other. There's an envelope, there's a message inside with RNA, DNA proteins, fat that are signaling, and then there's a signature, typically, to the exosome. And so, those messages, and the MSC are mesenchymal stem cells. So, you're combining exosomes, which are information, with mesenchymal stem cells that have the ability to heal. And now, what are those two together, how are they contributing to the healing process?

John Catanzaro: Well, with the peptide generation that we do that's specifically designed to the patient and you couple that with the MSCs, exosome MSC combination, then what happens is your exosome-MSC act as a carrier to get to the destination. So, in a lot of times, when that tumor is resistant, the tumor microenvironment has to be sensitized to the process. And the exosome MSC with the peptide coating actually couples a nice mix.

Dr. Jeffrey Gladden: So, with the exosomes and the MSCs, you're actually getting better tumor penetration with the peptides. Is that what I'm hearing?

John Catanzaro: Yes. Yes. You can enhance your ability to get into places that are much more difficult. But now here's the thing, is that the peptides are actually constructed in a nanoengineering structure. So, in other words, they are not naked sequences. They're actually engineered with a nano-carrying ability, so that they can get into tight places. They get across the blood-brain barrier, they're able to get into small vesicular areas. They're quite industrious that way.

Dr. Jeffrey Gladden: Right. Okay. So, the peptide, if you're thinking about a peptide being amino acids linked together, so you've got the peptide, but now it's being combined with other molecules that are actually enabling it to be transported through the body safely and to be able to penetrate various areas. And then, of course, we're talking about the MSCs and mesenchymal stem cells and the exosomes enhancing it even further to get to places. Is there a reason why that's not used for everybody, or what's the thought process there?

John Catanzaro: Well, the thing is, it's really important to consider when you're trying to address a resistant pattern in cancer, you have to really understand the metabolic implications. You got to understand the immune molecular signaling platforms. You got to know where the resistance is. So, for instance, the analytics, what they'll do is they'll plot the hallmarks of the disease expression. So, for instance, when we are doing the analysis, it'll say this gene is responsible for the heavy proliferation or it's involved in very extensive vessel manufacturing, which is known as angiogenesis. Or it's demonstrating an evasion to the immune system, which creates the resistance. Or it's a heavy trafficking signal that's actually related to the tumor microenvironment.

So, those hallmarks are; also, they're characterized and ranked. So, you're actually getting what is the gene protein and, what is it doing, and how is it influencing the cancer behavior. That's the reason why these peptides are so powerful, is because when they're programmed to those hallmark expressions, they're going after the environment that's actually the resistant elements of the environment basically.

Dr. Jeffrey Gladden: There's a company in Greece called RGCC, and we've been working together with John. We have some patients in common and some patients where we've done the analysis through Neo7 and the peptides have been developed, and patients are in the process of getting them at this point in time. And we all also use this company in Greece called RGCC. And when they identify circulating tumor stem cells in the blood, they're also able to sequence the DNA of those tumor cells and develop a molecule, an SOT, if you will, that is specific to the cancer DNA that basically inhibits DNA replication. And so, in talking with John, sometimes we're looking at combining an SOT with the peptides and then thinking about the mesenchymal stem cells, the exosomes, and things like that.

Because cancer is this multiplex of things, and you really want to come at it with more than one strategy to try to outperform it. Right? Because it's a robust survivalist, so to speak. So, it takes a lot to knock it out.

John Catanzaro: Definitely. That's true.

Dr. Jeffrey Gladden: And then let me ask you this. What about the patient's immune system? Because, ultimately, the immune system, when we're young, a lot of times we have a robust immune system, a malignant cell might develop, but we recognize that, we destroy it, things like that. But as we age, the immune system weakens, and we become more vulnerable to cancer. Are there strategies that you also utilize to boost a person's own immune system to help them have it rise back up? Because I know the cancer cells tend to both evade the immune system and suppress the immune system. So, to be able to rejuvenate that and reinvigorate that would seem like another strategy that might be super helpful here.

John Catanzaro: Absolutely. Along with what we're doing, we create what we call the adjuvant effect, where you're using an adjuvant that's actually nano-constructed. Again, that's a specific job, getting the immune system postured to better survey the cancer and induce a defense regulation against what's causing the resistance. And so, we'll use things like thymulin and peptide, and some of these other things that naturally raise in the gamma interferon levels in the system as well as the interleukin-2 pathways. A lot of these defense cascades. So, the peptides themselves that are tailored to the patient will actually naturally induce that type of activity anyway.

But then, when you want to have a more concentrated effect to optimize, then you actually start focusing in on those cascade elements of the immune system that will actually help with the recruiting aspect and better surveillance, better defense posture, and a better regulation.

Dr. Jeffrey Gladden: So, those would be peptides like thymulin or thymosin, thymosin alpha 1, or some of those-

John Catanzaro: Yes. Correct.

Dr. Jeffrey Gladden: ... kinds of peptides that have the ability to boost the immune system. And just so people understand what adjuvant is. An adjuvant is basically something that you use to sensitize the immune system. So, it's like training the immune system to go after something. So you're going to train your bird dog to go after the bird. So the adjuvant is whatever it is that's on the stick that you're training them with. So, that's what an adjuvant is.

John Catanzaro: That's it.

Dr. Jeffrey Gladden: Exactly. That's cancer. And what success rates do you have with people? How does this work out? Because cancer is difficult. Right?

John Catanzaro: It's very difficult, and it's a constant forward evolution for us. When we first started back in 1998 when the discovery happened, and then moving in from 2001 to 2014, we worked with, as I said, over 500 patients specifically with this type of design. And now, with G2 and G3, we're actually recruiting a lot of patients in. So, with generation one, we actually had a 55% objective response and getting tumors to reduce in size and even regress completely to extending longevity and good quality of life. And then with our new generation two and three, we're pushing closer to 72% because the thing is, is that, and look, we've got a long way to go because our goal and objective is to get to the 80% mark, but we really need to get a lot more patients and do a lot more design so that we can really tighten up the process.

Dr. Jeffrey Gladden: I assume that this treatment is something that people don't seek out first. I suspect most of the people that come to you have already been treated with some round of chemo or two or three rounds of chemo, maybe surgery, maybe radiation, whatever it is. I think people that are coming to you are already reasonably advanced in their treatment protocols, I would think. Is that correct or not?

John Catanzaro: Yeah, that's true. And we wish that we would get people a lot sooner because the sooner you can get them into this process that they're experiencing, we can get them in the early stage process. We have a really prime opportunity to prime them in the right direction. And not to say that we're not having success in late-stage cancers because we are, but the whole point to your question there, Jeff, is really important because the earlier you can get somebody in, the better the coordinated events can actually happen and less stress and complications on the person's own system. It's like, yeah, we like to be able to see this early on for people.

Dr. Jeffrey Gladden: I think one of the key things there is that most of the routine, blunt-force approaches to cancer, chemotherapy, radiation, and even surgery, tend to beat up the person. We know that it is ageism. We know that it beats up their immune system. So, now they're trying to fight from even deeper into a hole relative to where they are from health. Now they're trying to fight something that's resistant, which is a double whammy. So, if you can work with them early, then you have the ability to rejuvenate their less suppressed immune system. You're not trying to pull them so far out of the hole. So, I can see how that would be a great strategy.

John Catanzaro: Definitely, that's so true. And the other part of the process is that you move the person into recovery so that they're completely no evidence of disease, and then you can actually work on the next process of really getting their longevity up and helping with that programming ability because that's a whole new dynamo once you actually pull a person out of a disease process. And a lot of times, as you know, Jeff, because you've been working in this and you can see it, people when they actually focus in on their health, not on the disease process, that is, I would say a big part of the healing. That's a high percentage of their healing. Absolutely.

Dr. Jeffrey Gladden: Exactly. And I think one of the things that I'm talking about now is that really the medicine of the future, which is really here today. And I will say that Gladden Longevity is involved with Neo7Bioscience, and we are doing the testing relative to cancers and things like that and coordinating with not only ourselves but other practitioners in this area to make sure that people get treated. But one of the ways that we're thinking about this, the medicine of the future, is really looking at medicine through three different strata. And the most superficial layer is what I call reactive medicine or symptom-driven medicine. So, that would be traditional healthcare or traditional sick care as we think about it. So, the question I ask people: “Did you see your doctor today?” It's like: “Well, no, I feel fine.” And that's the kind of healthcare system we have. Right? You only go when you don't feel well, right?

And then you have below that is a stratum of functional medicine, which is basically focused on root-cause analysis, right? Okay, well, why do you have eczema? What's the root cause of that? Okay, your gut is leaky, you're allergic to gluten, you've got all these things going on; let's clean that up. And the next thing you know, your eczema is a whole lot better. That's root-cause analysis. But below that is another strata of medicine, which is called longevity medicine. And that's based on actually going after the drivers of aging. Because aging is an exponential process. It's a river that's flowing underneath those other two strata. So, if you're treating somebody for symptoms, well, that's all you're going to get. If you're doing root-cause, that's great, but you're still, it's sitting on top of this strata of a river that's accelerating in the aging process.

And that solution is only going to last for a period of time until it recurs or comes back, or you're losing resilience as you go along. So, this idea of actually treating people across all three strata is really what Gladden Longevity is devoted to. And that's actually turning back the clock on aging while you're solving the root-cause analysis, while you're also taking care of the symptoms. So, I think that, ultimately, leads to the most comprehensive approach to treating somebody to get them back to true health and basically give them back their robustness and their resilience so that they can really live a life on their own terms. And that's what we're talking about here.

John Catanzaro: Yep, most definitely. And I think that that's like, you really framed it really nicely there. Look, if you allow things to continue to smolder, they will, and then they'll become a raging fire. So, what you're really trying to do is you're trying to move that whole paradigm shift where it doesn't just become a symptom-focused thing, where you know as well as I do the plethora of drugs that are actually on commercials today or different things. And it's like- Look, I'm not saying- They may have a purpose, they may have an indication, but the point is that they're not going to solve the problem. They're not really going to move a person into a disease-free longevity and living a long and happy life.

Dr. Jeffrey Gladden: No, they're not there to increase your robustness and resilience. A lot of the side effects actually are decreasing your robustness and resilience, all the immune suppression, and all the other things that go along. I became- When I heard about John and got to know his company better, I started to think about longevity. If they're able to decode cancer, which is a complex activity, then maybe we could combine our knowledge and actually start to decode aging. And that's really the collaboration that we've taken on. And we've been working together now earnestly for a little over a year, I would say, although we've been talking for probably about two years.

And we created a new company called Genesis Longevity Bioscience, and it's really devoted to utilizing the transcriptomic and proteomic approach to decoding the aging process. Do you want to talk just a little bit about that from your perspective? And I'm happy to share mine.

John Catanzaro: Absolutely. It's been really exciting to work in this space because what we're seeing is a lot of relational value across the board. The hallmarks of aging, the hallmarks of disease, and hallmarks of cancer, they share a certain interface. It's like some of it is unique to its own hallmark expression, but some of it's very much relatable to the other and parallels the other hallmarks. And so, when Jeff and I got together to say, ‘well, what do you think about putting together something that's got an intelligent platform to really profile using the multi-omics, proteomics, and molecular phenotyping of the data points of the patients?’ I said, ‘absolutely’. So, we're using the same pipeline technology with a new developing pipeline technology that we're doing together with Gladden Longevity. And so, we've come quite far within the last six months. It's like we are getting down to the very fine focus.

It's been really amazing to watch, to see the whole sea selection at first. It's like the vast ocean getting into that more finer focus into, and now we're getting to the point where we're seeing the correlative value, not just plotting the problem and trying to create the diagnostic profile, but we're actually moving toward what we're seeing is a solution-driven movement, and how these various type of clinical strategies or treatment strategies will impact in a very, very positive way the person's data points. So, we're analyzing them interval to interval to see what the changes are and how we can impact the person's own transcriptome expression. And we're starting to see some of these different responses along the way.

If a person is hit with a virus and they're really down, and we get to see a down expression, if they're actually being pumped up with some good longevity integrations, boom, their values start to climb. So, it's pretty amazing to see how this whole thing is developing. So, I'm pretty pumped about it.

Steve Reiter: This episode of the Gladden Longevity Podcast is brought to you by FocusCalm.

Dr. Jeffrey Gladden: FocusCalm is a headband that uses neurofeedback-guided meditations and relaxing games to help you manage your stress and anxiety, help improve your mental performance, and so much more.

Steve Reiter: Using the FocusCalm a few minutes a day for three weeks can improve your sense of mental well-being by up to 21%. Enhance your daily wellness routine by building habits to help you feel and sleep better.

Dr. Jeffrey Gladden: Right now, you, our Gladden Longevity listeners, can get 10% off of a headband and a lifetime subscription when you go to focuscalm.com, that's focuscalm.com, and enter the promo code ‘Longevity10’.

Steve Reiter: I've used the Muse headband for my meditation and neurofeedback since 2016, and in my opinion, I like FocusCalm better. With meditations like Stability in the Uncertain, Overcoming Aimlessness, Living in the Flow, Clarity from Cognitive Burnout, Stability from Distraction, and many more. FocusCalm headband is an upgrade, in my opinion, and is now my go-to when I take a break from work and recenter my mind. So, once more, that's focuscalm.com, and use the promo code ‘Longevity10’, to get 10% off your headband and the lifetime subscription.

Dr. Jeffrey Gladden: What I've enjoyed about it is actually seeing the depths to which my meditation takes me. It's like instant feedback. It's such a cool thing. It's like you think you're meditating; well, how deep are you? And then, when you go really deep, and it maxes out at 100%. It's like, ‘okay, I guess I just got there.’ Although as soon as you look at it, you drop down to 60. But it's fun. It's really fun. FocusCalm, train your brain to better focus and a calmer mind.

It's really fascinating because we've been measuring a mosaic of ages for a long period of time. We all have a chronological age, and we all have a birthday, but then we're really a mosaic of biological ages. So, we're not just one biological age. And yet we know that there are drivers of aging, hallmarks of aging, if you will, that with all of our testing that we do on the mosaic of ages, we've been unable to get to. We can't really measure proteostasis. We can't really measure the secretory status of senescent cells. We can't really measure senescent cell burden. There's lots of things that we can't really measure. We can't measure the balance between mTOR and AMPK; that's so essential for longevity, et cetera. So now, all of a sudden, with the ability to look at messenger RNA, the transcriptome, and protein expression, we can actually start to look behind the curtain and see what is actually working.

If we're taking NAD, right? If we're taking resveratrol, if we're taking pterostilbene, if we are taking different things to activate sirtuins, if we're doing intermittent fasting, if we're using young plasma or plasmapheresis or using rapamycin, a lot of things that are involved in our LIFE-RAFT trial that we're doing, the IRB approved LIFE-RAFT trial that we're doing, now all of a sudden using the Genesis Longevity Bioscience, we're calling it an LRI LIFE-RAFT index testing, we can actually track changes for people, because if we're making people younger, we should be able to see it in their DNA expression, i.e in their proteins. And it's really fascinating to see that.

And one of the things that's exciting is we're looking to see how young plasma, which has a different set of proteins in it than older people's proteins with plasmapheresis, we take out the old and put in the new, and then we can measure downstream and see what impact is that actually having on the expression of their endogenous protein. This becomes a really fascinating thing, and I love the fact that we're doing this because it's really all about precision. And when we're just guessing at things, you do the best you can. You have a hypothesis; well, this should work well; taking resveratrol should be a good thing, but you can't really measure it. And now, all of a sudden, we can look behind these curtains and actually see, okay, what impact is it having? It's super exciting. I'm so grateful to be working together.

John Catanzaro: I am too. It's just a very fascinating development together. And the other piece of it is that with the program when we talk about polypeptide programming in addition to all of the very powerful longevity therapies that are out there, you can actually take a core engineering gene set that has a very positive expression on a particular gene set that maybe doesn't look very healthy, and you can impact that through the polypeptide programming pathways again. So, in other words, it has a very positive editing effect going back to a very potentially negative type of profile.