Klotho, Peptides and Limitless Longevity — Dr Alex Grinberg and Dr Dave Jenkins

TRANSCRIPT

Lisa: Well, hi everybody. Welcome into Pushing the Limits. Today I have an absolutely super exciting episode for you. I have two gentlemen who are just at the leading edge of longevity medicine, immunology, psychiatry, Alzheimer's, you name it. These two gentlemen are just absolutely brilliant. I have Dr Dave Jenkins who's been a repeat guest on the show. And this week we also have the incredible Dr Alexander Grinberg who is an MD from the US and practices in the San Francisco area but he has an incredible background history. So welcome to the show gentlemen. Dr Alex, because Dr Dave's already been on the show, can you give us — because I know that I will muck it up if I tried to give your biography, it would just not do it justice — would you tell the people a little bit about your background? Because it's quite an incredible background. So over to you Dr Alex.

Dr Alex: Lisa, thank you so much. It's a pleasure and honour to be on your podcast. Thank you. So as you mentioned, I'm a physician MD practicing in San Francisco, California. And for many years, for decades, I've been helping people locally in the United States and internationally in many different countries, helping them to develop advanced customised protocols, helping them with longevity, with reversing their aging, rejuvenating them, making them stronger and more resilient, but also helping people with a number of grave conditions that with conventional medicine would have very grave prognosis. And getting into these puzzles — each case is a very deep puzzle — and finding out how to combine the most comprehensive advances in developing experimental biology and medicine to help these people and alternate the outcome to a good one.

Lisa: You have also an incredible history in peptides. You understand immunology as well. You have a fellowship in immunology. You've also studied psychiatry. And you're very well known in the peptide space and you teach a lot of physicians as well in this space. So you have a really deep knowledge across so many areas that it's not going to do it justice to fit it all into today. But just to say that you are the people that all the wealthy people in the world go to to basically get healthy, stay healthy, and also complicated cases. And I'm going to be bringing my mom, which is a complicated case, to you shortly. But Dr Alex and Dr Dave, now you are both working on some projects together. And Dr Dave of course is expert in the Bredesen protocol in Alzheimer's and neurodegeneration. And how did you two meet and how does the relationship work with you both?

Dr Dave: We met because the first time I ever listened to Alex, I knew I had to — I didn't know what would happen — but I knew I needed to talk to him because the complementary skill sets and our approach. And so I just contacted him at Infinity Epigenetics, he got straight back to me, we talked, and then this bunch of projects that we are working on together. It looks very exciting. Very, very exciting.

Lisa: And Dr Alex, so give us a bit of a rundown. You're working with Dr Dave on a longevity clinic at the moment. Can you tell us a little bit about this project? There are a lot of longevity clinics now starting around the world. What makes you different? Because you're very different and you're very much at the cutting edge of this. Can you share a little bit about what your vision is?

Dr Alex: It's a pleasure. And by the way Dave, thank you so much for your presentation. It was a pleasure meeting you and I enjoy our interaction and finding a like-minded physician and scientist. So my main interest for many years was the high-level integration — or I would say integration on a high-end level — of advanced therapies. It's not just only peptide therapy or micropeptide therapy, but how it combines with regenerative medicine, how these fields of advanced medicine can complement each other. And then the genetic therapies came into the picture and I started working on integrating all three — peptides, regenerative medicine, and gene therapies. It's a very complex area where I'm providing consultations and teaching for physicians. I call it high-end integration and customised medicine, and that's why we have this podcast today. That was our focus, that was the main topic. We became friends and colleagues with Dr Dave Jenkins because he's also very interested in that. And I believe that in today's world, where a lot of people talk about longevity and create different approaches, I want really to develop limitless longevity where we are not limited by pseudo-ethical or pseudo-legal restrictions, or in the case of people, personal decisions — how far they want to go with longevity, their health. They may have very diverse budget and diverse portfolio, but it's up to them which decisions to make and what to choose. Where people have liberty to do that in this environment, we can provide higher-level integration. So we can bring the best of the best modern experimental therapies — but I would remove the word experimental because we developed the ways how to mitigate the risk of something that no one before this exact patient got. And it's not statistics where how 50,000 people responded to it and how many percent had a side effect. That's a precise way of cultivating and banking cells from the same person and creating cell culture and predicting what effects or side effects we can see in different cell cultures. It's part of that. So it all can be included. It was done. We can do not just some multi-marker test and give a rough prediction. Instead we can do rapid analysis of thousands of tubes with the same patient's cells and tissues and predict in which tissue, in which cells, which changes in gene expression and overall longevity. We can do accelerated longevity tests. We can do accelerated cancer tests to see resilience of these new cells against cancer, for example. So we can provide the most accurate and comprehensive and probability-controlled individualised — you can say decentralised — trial for the customer. So that's where the person can choose which interventions can be applied. Because before we harvest cells from someone, we need to make sure that the person at age 70 has their cells good enough to give good offspring and expand them. Like maybe they have already short telomere attrition or mitochondrial issues. I want to fix them a little bit on a customised protocol to prepare their cells to be autologous — to be their own cells — and to be reprogrammed and expanded to so many different cell lines that can really extend their life.

Lisa: Wow. This is just absolutely amazing. So it's really personalised to the genetics of the person, the age, the status of the person, being able to get really targeted interventions for that specific person. So using epigenetics. Dave, have you got anything to add on that side? Incredible.

Dr Dave: As you know, I keep an eye on things and am connected quite well in this space. I've never heard or heard of anything this advanced. So essentially you're getting a mini me, a mini patient in a petri dish, and you'll be able to say which one — let's test this out, how this person or this cell line is going to respond best — and then work out all the potential risks. And it just takes longevity to a completely different level and a different level of safety as well. And like Alex said, the ability to make a decision is a very complex thing. And that's the role of Alex and myself — to be able to understand it and communicate the risk versus reward. So yeah, I can't believe I'm sitting here being able to learn this new science from Alex and then we will be applying it in the clinic that we're working on.

Lisa: Yeah. And this is where it gets really exciting. I mean, I love being at the cutting edge trying to understand to the best of my ability what's going on in the world. And I am completely frustrated all the time at how backward our governments are and our medical institutions that are very, very slow to adopt new technologies. And meanwhile, people are dying and getting sick when we have the abilities now to actually do a lot more. And you have the right to — you should have the right to try — especially when you're at the end of life or you have a particularly difficult situation, or you choose to. And I'm very passionate about the right to try. And I think this cutting-edge stuff is so powerful now. We can do things, and I've experienced it in my own life with my mother who had a terminal brain cancer and we were told she would never ever survive, there was nothing that they could do. And I took that into my own hands and I did as much research as I possibly could. I developed my own protocols. I did advanced genetic testing. And the people who follow me know my story. And she's now, you know, for nearly five years later and cancer-free. Got some other issues that I hope Dr Alex can help me with. But we have this power and I see people dying left, right, and centre or being very sick and maimed and not getting access to this information. So I'm very passionate about sharing this really cutting-edge stuff that Dr Alex is talking about. Dr Alex, explain a little bit deeper about what this clinic is going to be doing. And we are talking about this today because we also want to bring it to the attention of people because this sort of clinic needs investment. We need people to help get this going off the ground, and there are people that are really interested in this area. So tell us a little bit more about what people can expect from this clinic once it's going.

Dr Alex: Excellent. Thank you for asking this. And I want to say that you mentioned that one of my specialisations is psychiatry. I know that for people it's very important to understand the ratio of risk and benefits, and I'll first talk about this clinic and then I'll get back to this and it will be very helpful I think. So luckily, among people who have seen the benefits of customised medicine and all advanced medicine are people who are in governments of certain Pacific Island nations, and they are very progressive and they're willing to accommodate the organisation that will provide this access to limitless longevity and limitless health. And for me, thinking about this is like achieving the ultimate goal in longevity, where we can have a place where we can provide the best materials, best vetted materials from any of these novel blends of medicine — be it proteomics and Klotho proteins or peptides, micropeptide medicine, regenerative medicine with all kinds of stem cells, novel stem cells, and related products like exosomes and secretomes and different factors from them and other cells like immune cells and NK cells. And over there we can combine all of them with, if necessary, gene therapies. And we can work with the best biotech labs in the West who will reprogram the cells and do these deep biology interventions when we need to go far and reprogram someone's own stem cells or other cells and create the next layer of longevity interventions. So it's all a dream that we can materialise there because we can do all of that without limitations on dealing with these materials and their clinical application. And at the same time, helping the local population with certain metabolic and highly epidemiologically present conditions. So finding the ways to help everyone and assure the basic right to live as long as you want and as good as you want.

Lisa: Amen.

Dr Alex: And talking about the probabilities, I know I was working with different companies and investors and I know that investors have good groups of analytics and a good approach comparing the risks of investment and loss and all these financial things. So here I would encourage people who are potential investors or looking for these high-end treatments to consider the risks of dying in the next 20 years from cancer or cardiovascular disease, atherosclerosis, or metabolic condition, or autoimmune conditions. And then consider what is the risk of starting to get basic health improvement things with very well-checked and high-quality peptides and customised peptides to their genomic setup. To work with some very well-studied stem cells and exosomes and what would be the good response. It's not some exotic marker. It's if a 75-year-old executive sees that after six months of treatment his level of testosterone is up 20-30%, isn't that a good marker to see? I always focus on personal improvement, how people perceive it. So they get higher levels of testosterone, higher levels of nitric oxide production or response to it. They get better insulin-related things — down HbA1c, down insulin resistance — and so many other things. They lose 20 pounds and they can move better. And that's the first line of improvement. Then we can check — are the cells improved in terms of telomere lengths or mitochondrial and immune functions and so on? And then we can base the next step of longevity on improvement achieved first. And then we will see other risks based on genomic analysis — what can be a longer-term potential weakness in the body — and we can pre-emptively target this one. But this is basic good level of traditional medicine that we will see probably in five to ten years.

Lisa: Yeah. And you'll be able to do it now.

Dr Alex: Then we add more high levels of complexity using, say, autologous NK cells to clean senescent cells. We use patient-derived exosomes that improve either regeneration of some organs or reduce fibrosis. So many things. Unlimited use of that and improvements.

Lisa: Yeah. Dr Dave, what do you have to say to all that?

Dr Dave: Yeah. Well, I'm very excited, and it's probably pretty obvious. But one of the things — the total project, the total outputs from this project — like Alex said, we're going to be helping the local people. It's not just for people who can afford these therapies. And the second thing is that I'm passionate about training, as Alex is, physicians. And I'm of an age where it's time to give back and train. And so we'll be training the local staff. But it's very pertinent in that the risk of any investor is so low because we don't have to build — initially anyway — we don't have to build infrastructure. We don't have to find staff. The infrastructure from the country is provided. So we can go step by step at very low risk and we can build out based on experience and need. And the other thing from an investor's point of view is they will have very personalised attention from Alex and myself. We'll be two grateful physicians. And also, they can — the return is — when they bring their friends along then they're going to get a return on what that person spends. So yeah, it's a win-win. Total win-win.

Lisa: Yeah. Yeah.

Dr Dave: And I have friends who are looking at it, interested in it. But they have to overcome — everyone has a bias — and so you need an appropriate mindset and to sit with it from time to time and ask us questions.

Lisa: Absolutely. Because this is really cutting-edge stuff and it really is — I mean I've spent years sort of studying this stuff and interviewing physicians. I've got a bit of an idea of what some of these things are, like Klotho and follistatin and peptides and all of these things. But a lot of people don't. And so the second half of the podcast today we might dive into some of those actual therapies that might be involved. But just to round out — I mean I'm of Maori descent, I come from New Zealand, I'm Maori — and our people and the Pacific Island people have certain genetic predispositions towards certain diseases and they're quite rampant. Things like diabetes and metabolic diseases, these sorts of things. And so being able to give back to the population in this clinic will be a big part of the whole thing as well. And I know Dr Dave, you've done so much work both with SurfAid, with the projects that you've donated your time. You've generously given back to humanitarian — let's put it that way — you're a great physician and someone that I totally admire for what you've given back to the community as well as what you're doing now. And you're also really going forward. And I just want people to be able to have the choice to be able to do these things if they want to. And also, over time the more these therapies are utilised the cheaper they will become. Initially these are going to be a little bit more expensive, but as you say you will be giving back to the local population. But over time these therapies will be democratised. But we have to actually use them. The research that comes out of these clinics as well is going to be very powerful for bringing it forward, bringing it into the current world. So Dr Alex, tell us a little bit more. So you run Infinity Epigenetics and you're also on the advisory board for many Silicon Valley biotech companies, that type of thing. What are some of the therapies that you specifically are using now in your practice? And what do you see as being the latest, greatest things? Would it be like if we started with Klotho, for example? Tell us a little bit about some of these cutting-edge things like Klotho and follistatin and all of this.

Dr Alex: OK. So I guess many people know about Klotho and some basic information that I can add with some more specific description. So it's probably one of the elixirs of youth, and it's responsible for a lot of organ rejuvenation — rejuvenation felt subjectively. And there are a few forms of Klotho protein. Scientists mostly focus on alpha-Klotho protein. It's the best studied. And there were a lot of correlations found that a lack and drop of the level of alpha-Klotho protein correlated with increased morbidity and mortality for many main diseases — for cardiovascular, for cancers, autoimmune conditions. And obviously with restoration of Klotho levels in the body, there are also some positive changes. Reduction of overall inflammation, more activity of a person's own stem cells — like endogenous stem cells — and probably improved metabolic conditions and so many other things. So at this time there were attempts to bring the Klotho as an injectable form, either pre-manufactured or — while it has some pharmacological difficulties in delivery — the attention is on gene therapies, mRNA-based or plasmid-based delivery of coding Klotho protein genes. And according to my knowledge — and I interact with companies working in this field — it works very well. Scientists who developed this are trying it on themselves and had very good results.

Lisa: Yeah, I've interviewed one or two.

Dr Alex: And then of course more people and more patients in different areas. And they were followed clinically. They're doing very well and only positive changes were seen with this therapy. And this is not altering a person's genes. It only adds information that is coded and transcribed for about two months. And it's kind of a prolonged form of therapy but it's not irreversible and it's not altering the host gene — it's very important to understand. But I see very good results with this therapy. And there are also peptides. They are fragments of the larger molecule of Klotho protein. They're also very good. They have a very small size compared to the Klotho protein molecule but they can penetrate everywhere — the blood-brain barrier — and they have better intracellular penetration of course. And they have many miraculous, great effects as well. There are different ones — Klotho peptide 1, Klotho peptide 6 — and as initially Klotho protein was found and expressed by kidney cells, they have a lot of good work in the kidney. They reduce kidney fibrosis, slow down diabetic nephropathy. So they're amazing peptides and probably other fragments of the Klotho molecule will be better described and characterised. But that's what happens in the Klotho industry. And we see — Dr Jenkins has seen a lot of improvements reversing some dementias, and I've seen a lot of improvements with Klotho in different conditions — chronic dystrophies and some other neurological conditions, multiple sclerosis for example, autoimmune conditions. But I think Dr Jenkins has a case about Klotho.

Lisa: Yeah, do share your case experience, Dr Dave.

Dr Dave: Well, we've got nine cases. So we've been using it with people not only with early cognitive decline and Alzheimer's but head injury. And so I've got two patients who had chronic head injury. We did improve on a programme with them. They got to a certain level. And one is a doctor who had such a good response to Klotho — he had to resign as a doctor, which was very hard for him. He's a passionate doctor. And he couldn't practice medicine after his head injury. And he told me the other day after his Klotho, "I'm going back to medicine." It was a very good day for all of us. He had such good cognitive response. And I have another head injury patient who couldn't afford the full gene therapy but I said let's give you a nose drop. So we put the nose drop down through the cribriform plate. He was a rugby player — chronic head injury from rugby — and he's much better. Much, much better. And we documented this. This is not subjective. This is objective documentation of cognitive scores. And one of the surprising things was — myself, I thought, well, it's a natural protein, it's in every mammal, there's 300-400 people who have had it, there's not been one serious adverse event. And I thought, well, I'm going to have it myself. And so I lined up, had my injection, and my composite memory score went from the 66th percentile to the 97th.

Lisa: Wow.

Dr Dave: My memory scores in six weeks. And I can tell you, this is an extraordinary experience for me. It's like being an 18-year-old medical student consuming all this information. And my brain is back. And I'm going to struggle to let it go back down. I'm probably going to keep having the Klotho protein. But it's exciting from a perspective of being able to address this terrible number one killer of women in Australia right now — Alzheimer's.

Lisa: Alzheimer's.

Dr Dave: And so we can now offer them and it will get cheaper. And as Alex said, there are different forms. There's the Klotho proteins, there's the plasmids, and the full gene therapy. So hopefully with time this is going to become more and more affordable.

Lisa: Yeah. So I interviewed someone who was — I think — the first person to have the whole Klotho gene therapy. I'm not sure whether it was a plasmid. I think it was the viral vector. I don't know the name of the actual way it was delivered. But that isn't like — the Klotho is a very big protein that normally can't be delivered just in an injection, can it? It's not — so these Klotho peptides that you were talking about, these are fragments? So these are little tiny pieces that can pass through into the mitochondria, Dr Alex, or into the cell? How does it actually work in the body?

Dr Alex: Definitely. They are cell-penetrating peptides. And for them, the main scientifically identified targets are fibroblast growth factor 21 and 23, corresponding to these different peptides. And these fibroblast growth factors — they're involved in the process of excessive deposition of extracellular matrix as fibrosis. When, in simple language, the organs become tightened by pieces of connective tissue that shouldn't be there. And it limits the perfusion — blood perfusion — and squeezes them.

Lisa: So this would be very good. I've got a case for you gentlemen. So one of my clients — I won't name obviously — but he has chronic kidney disease. So the kidneys are very impacted. He's had hepatitis and also has liver fibrosis. He has high mercury toxicity. We can't do chelation — the normal types of chelation — because it's too damaging to the kidney. Would something like this Klotho or other peptides — mitochondrial peptides perhaps — be a good approach for such a client with fibrosis of the liver?

Dr Alex: I want to use this case to give people an example of what is the high-level integration in customised medicine. And that's what we do in seminars — just finding the case and immediately working on solving it. So obviously for him, considering his damaged liver and kidney, the main factor is ongoing mercury toxicity and we want to remove mercury. But if we use standard methods like chelation and chemical methods, it can overwhelm all cells with mercury that dissociates from chemical bonds. And that's why we look for other alternative methods to remove mercury, like INUSpheresis.

Lisa: That's something I've been looking into.

Dr Alex: But what to do next? Because even while we're doing that, his kidney and liver function deteriorate and we want to stop deterioration of kidney and liver function. Even while we're working on removing mercury, we can start him on certain peptides that will help to at least stabilise the systems in kidney and liver to stop the worsening of the condition and support them — support the mitochondrial functioning, support the elimination function. At the same time, it wouldn't interfere with INUSpheresis. And then we clean his body from mercury. And blocking the toxins with certain peptides, we can think about immediate regenerative medicine which would be focusing on companies that have files with the FDA — some scientifically substantiated effect of the exosomes or cells on certain fibrotic conditions. There are such companies. So from my personal experience, I use companies that work with the FDA for these indications and use it for my patients and have seen tremendous reversal of liver cirrhosis. For a person who had weekly — sorry, monthly — hospital visits to suck out ascitic fluid. This is what accumulates in the layers covering the abdominal organs. When people have cirrhosis, a lot of liquid — up to 10 litres. And after a few injections of certain exosomes, she stopped building up the ascitic fluid. And she was improving — bilirubin level was improving — and eventually after six months we saw some positive changes on ultrasound and liver CT scans. So it was a combination, and we continued alternating or combining certain peptides and the regular treatment with this regenerative medicine product. And the person is very happy. She's back to fully functional — cooking, helping her family. Absolutely happy.

Lisa: And that's not usually something that you can fix. This is not something you come back from normally.

Dr Alex: No, it's usually a terminal diagnosis. Some of the saddest cases in my memory — liver failure.

Lisa: And in fact, I lost a good friend to liver failure just a few months ago.

Dr Alex: Yeah.

Lisa: And if I'd only known that these therapies were available.

Dr Alex: Yeah. Exactly. Exactly. And that's why we're doing this.

Lisa: And what are some of the other peptides that — I listen to you on Dr Fiona Chen's podcast. You've done quite a number with her. She's brilliant. Talking about mitochondrial peptides — you've got your MOTS-c, you've got humanin. Can you tell us a little bit about the mitochondria, what — why the mitochondria are so important for ageing and what happens when they go dysfunctional and how the mitochondrial peptides perhaps may be of benefit in stacking them in these sort of ways?

Dr Alex: OK. I will explain it straight and efficiently. Mitochondria are our little energy stations. They're small generators of energy in our cells, in each of our cells. And just for interesting information, billions of years ago they were bacteria. They occupied our cells and then found a symbiotic way of coexisting. And they still have their own genome. The mitochondrial genome is very different from our main genome where we have our nuclear genetics. And it's a very small circular genome of 20,000 genes. And they code also for other mitochondrial peptides — humanin-like small peptides, or small humanin-like peptides — you can say from 1 to 10 numbers, there are so many of them targeting specific — they are micropeptides, they target specific very intimate functions of mitochondria. So as mitochondria are energy stations, probably it's obvious that any cell needs energy. And if it's a lymphocyte searching for a virus or an NK cell searching in the blood for cancer cells, they all need a good engine. And that's fuelled by mitochondria. Same for brain cells — we need a lot of energy to think and memorise things and produce dopamine and serotonin. So anywhere where cells experience mitochondrial illness, mitochondrial attrition, we see pathology — be it a rare form of muscle dystrophy or some special form of dementia or cardiovascular condition. It's everywhere mitochondria are involved. So mitochondrial peptides have different functions. MOTS-c helps mitochondria to rejuvenate, to eat its own parts when a part of it is too old and not functional — called autophagy. But also MOTS-c is much more interesting than that. It travels — it's a messenger between the mitochondrial genome and our main genome. It can travel back and forth at times of cellular stress. And it gets — mitochondria borrows this peptide to the main genome where it stimulates better metabolic flexibility and better cell resilience. So it's a very interesting peptide. Obviously it's native for our body. They're all not external peptides. They discovered it in our own cells and tissues. And SS-31 peptide targets the cardiolipin layer in the mitochondrial membrane. And working with that, of course, for mitochondrial energy production — and the important charge on the inner and external level of the mitochondrial membrane where the electric current happens and stimulates mitochondria — and that's very important to affect the proper layer in the membranes. But it helps many kidney conditions and helps with neurological conditions because they're all organs that depend extremely on energy production. Kidney, heart, and brain. And this peptide also reduces lipid peroxidation inside the cell. Not oxidation but peroxidation that's damaging for cells. So it's also a great function. And humanin is a small peptide coded inside the mitochondrial genome. It regulates many processes across the mitochondrial membrane. But it has an amazing function. It stops cells from dying. So if some cells of the body are on a premature way to death because of some toxic exposure or virus, but it's still not past the point of no return, they can be resuscitated. And humanin helps them to get back. It's not saving senescent cells, but it's saving cells that are on the way to apoptosis but can really get back to normal function. So it's very important. And in many conditions it helps, in the beginning of a protocol, to at least slow down and stop the pathological process — to save cells from dying.

Lisa: Yeah. And so mitochondria are really at the basis of all disease really, because they are the energy producers for each of the cells and each of their jobs. So it's really, really important. And then you can stack these together, can't you, Dr Alex? You can put the SS-31 and the humanin and some other peptides — even like BPC-157 and thymosin alpha-1 and Selank — for different cases, for different situations. But that's where your expertise comes in, in dosing them correctly too. Because when you look at the peptide landscape and you listen to a lot of biohackers and stuff, sometimes they're very aggressive with the dosing of the peptides, and it can be dangerous too. Like if it's not done correctly — SS-31, for example, can be quite a stimulating peptide — you might want to be micro-dosing dependent on the specific case of the person. And this is where this level of personalisation is what you're able to do with what you do. Is that correct?

Dr Alex: Yes, absolutely. And thank you for bringing up this subject. Because in the area of experimental medicine, even advanced customised care, frequently physicians ask me this question — is it only 500 micrograms of MOTS-c or is it only 50 billion of this mesenchymal cell exosomes? And I have explained again and again that it's an algorithm based on constantly changing variables in the patient's system. But to be on the safe side, I always start with micro-dosing any peptide. Before that, I start with skin testing of the peptide, because rarely they have some immunogenicity, or for some people with higher sensitivity there could be immunogenicity. So I start with skin testing and then proceed with micro-dosing. And both clinical follow-up, laboratory follow-up, and observing and listening to the patient also for certain subjective changes. And with mitochondrial peptides, as with any other peptides, it's extremely important — like you mentioned — proper dosing and then proper sequencing. For different conditions — in some conditions, I would give you an example — in some conditions, a young and strong person, let's say after some viral infection, has damaged mitochondria where you can help with MOTS-c because they need help to autophagy their damaged parts and rejuvenate. In some person with stage 3 kidney disease with an autoimmune factor as an important pathogenesis, you can activate immune cell engines with this active mitochondrial intervention — they can attack the kidney or transplant more aggressively. So it's all case by case. And even humanin, being an amazing peptide, in people with a history of cancer or being on chemotherapy, excessive humanin can activate pro-tumour pathways and we don't want that. So it's utmost consideration.

Lisa: And this is where the personalisation and the specifics with that person is just absolutely key. And not just listening to some expert on YouTube or Instagram and going, "Oh, that's the dose to put in." It's a lot more complex. And then stacking them correctly. Dr Dave, what's your experience with peptides? I know that you're a big fan of peptides too. And we've lamented at how difficult it is to get peptides. But you've used them extensively in your practice as well.

Dr Dave: Yes, I do. I tend to stick to the ones I'm gaining experience with, and I'm quite conservative with peptides. But especially in the brain area, we have seen success. And yes, I like to use SS-31 initially to repair any mitochondria and then use MOTS-c after that to sort of stimulate mitochondria that's repaired. I do like some of the peptides for the brain — Semax, Selank, and Dihexa as well. I'm using that with a Parkinson's client at the moment. It's very, very potent and we have to be quite careful with it. So we tend to pulse. Dihexa has quite a long half-life. And so I tend towards cautious. And also we have to be careful about the purity of the peptides.

Lisa: Yeah. This is because the bonds of peptides, if not done properly, are bound together with microplastics and even styrofoam. So you have to be very careful about where you get your peptides from. And that's a big concern. There are a lot of people with a very cavalier approach and are whacking themselves with all sorts of different peptides from various Chinese and other providers. And I have very big concerns about that.

Dr Dave: Yeah.

Lisa: And Dr Alex, you too. You've mentioned on other podcasts being worried about some of the cowboy, wild west situation with the peptides.

Dr Alex: Yes. Well, as always, I would say some companies in the US and China may produce very high-quality peptides. But again, I'm for batch-by-batch testing and using vetted third-party labs to do it. And I'm in the US. I'm collaborating with high-level institutions that work on peptide research and development, lead optimisation, preparing them as candidates for big pharma. They work with very reputable labs where we can get analysis. And if we're working on high-level limitless longevity, I would spend some part of the investment — of what we spend — for good vetting and assuring the highest quality for peptides, and doing biological assessment and characterisation for stem cells or exosomes as well.

Lisa: No, absolutely. Sending it to associated labs. Yeah. Sorry, Dave.

Dr Dave: You know, I think that's one of the big advantages of the clinic when we get it open. We will have every peptide vetted and they will only come from the very best. And so the patient will be very confident that they're getting the very best. And that is a rare statement to be able to say.

Lisa: Yeah. And so another reason to get this clinic up and running — so we can provide the world's best not only in the type of therapies but the quality of the therapies.

Dr Dave: Yeah.

Lisa: And what about — would there be other therapies offered, say things like INUSpheresis or like hyperbaric oxygen therapy, red light, photobiomodulation — those sorts of things will be offered as well perhaps?

Dr Dave: Yes. Definitely the INUSpheresis — we've already looked at that. And as we build out the clinic, it will depend on the investment, the degree of investment. But we have our wish list and — yeah, he has his and I have mine — and we will get it all up and running. And I think there is a lot of opportunity in integrated cancer treatment as well.

Lisa: Wow.

Dr Dave: A lot of opportunities to improve patient outcomes through Alex's natural killer cells, through repurposed medication. This is a particular area of interest of mine as well. I've lost family members to cancer that I think didn't really have to die. And so I'm going to put my hand up and delve into that in a big way. And not making any promises but we have to do it carefully and we have to do it very considered in documenting what works and what doesn't. But with AI, we can now analyse cancer survival pathways to a whole new degree and we can block those cancer pathways with repurposed medication. Now, another reason this clinic will have so much benefit is because the repurposed medication is deregulated. We don't have to ask the medical council for permission to use ivermectin, for example, or metformin. We can use it under the rules of the Pacific Island nation that we are working with, and we can comply with the rules. It's just that the rules will be broader. As you said, the right to try, and compassionate use — these will be the rules. It doesn't mean that they're unsafe. It means that we will be applying rigorous academic use of the knowledge to make sure they are safe. And we will invite scrutiny as well.

Lisa: You know, I've used off-label drugs for my mother's case and I know how powerful they are. When she was given weeks to live and multiple tumours in the brain — over half of her brain was covered in tumours — and they said there's nothing you can do. And so I did everything — advanced genetic testing to find out what immunotherapies, what chemotherapies she would respond to. And this was before AI. Now with AI, I could do it much more specifically — off-label drug combinations. And the great thing with drugs that have already been approved, gone through the clinical trials, and they're sitting there — and you as physicians know the pathways that they impact, and you know the pathways that need to be impacted in cancer. And so when you start to put those two together — and off-label drugs have been used for decades for cancer, but it's still not the standard of care. It's still only in that metabolic approach to cancer side of the story that the doctors even know about it. I mean, we use things like metformin and doxycycline and mebendazole and ivermectin and all of those things as off-label use to block the cancer pathways. Statins, even. All of these things can add — sorry, go, Alex.

Dr Alex: Thank you. So talking about drugs or repurposed drugs — of course, what we're going to create, we're going to move away from drugs and decode the patient's genome and use patient-specific peptides manufactured according to their specific genome. That's the goal. Move away from pharmaceuticals to the patient. The idea is to regulate the complex orchestra of internal signalling with customised instruments — like specific peptides according to pharmacogenomics and specifics of this patient's genome. That, of course, at some point — those are low-hanging fruits, repurposed drugs — but they're as good as any other drugs. But we want to move away to a much higher level of longevity interventions — to regulate faulty signalling with customised peptides. And that's — it's done already. And it's personally tested already. So it's not a fantasy.

Lisa: No. It's the next level that needs to be available to everybody. This has just been absolutely fascinating. Just coming to — I did want to ask you, Dr Alex, about the NLRP3 inflammasome, because you've done some research in this area. What is the NLRP3? What does it do? And are there some interventions that are going to help with this?

Dr Alex: Well, basically this is a gene that is responsible for developing a brain inflammatory condition, and combined activation of subgroups of interleukin-1 and turning on the caspase pathway that is very detrimental for the cells and can easily lead to developing these neurodegenerative conditions — dementia.

Lisa: Very, very scary. So yeah, and there's some good research going on in that area as well. Gentlemen, is there anything that we haven't touched on today that we should be sharing as well? Have I forgotten any aspect of what we've been discussing? Because I think we want to make sure that we've touched all the bases, that people understand. What I want to get across is that the research has already been done and there's a lot of it already out there and a lot of it needs to be actually got into clinical practice now. Like we need to — in New Zealand we are 30 years behind. When you go with your diagnosis to a local clinic, you're not getting the latest. If I had just sat back and accepted, my mum would have been long dead — multiple times over — not just from the cancer but also after the aneurysm and everything else that she's experienced. So I think it's really important that we push this science forward and that we get it out to the people. And is there any sort of last words that you both want to share to sort of round out this conversation?

Dr Dave: I think yes, you should. Having been a GP in New Zealand, I know that the workforce is very well intended and very professional in the scope of what they do. Just generally speaking, the doctors there are well trained and highly motivated. However, it is a case of they don't know what they don't know. And they just have no idea. I introduced a diabetes reversal programme, as you know, and we're going to be publishing that. And it's grabbed the attention of the top diabetic specialists in New Zealand. And it surprised me that they didn't even know about this protocol to reverse one of the big killers in New Zealand. And so hopefully we'll take that to scale. But that's just one example. Please do your own research. Reach out to functional doctors and people like Alex and myself for a second opinion on your condition. And don't just take what your doctor's telling you as being the only thing that can be done.

Lisa: And can people reach out to you? Can you work virtually with clients all around the world? Both of you?

Dr Dave: That's what Alex and I do. That's our daily bread. Even on Sunday yesterday, I was talking to a woman with breast cancer about her options in Dubai. She was in Dubai.

Lisa: There you go.

Dr Dave: And she had not been told by her oncologist any of the things I had told her. And so she will now go into chemotherapy doing the fasting-mimicking diet. Her results are dramatically increased — chances of improving, and her fatigue and nausea will be down. And it's changed her life, just a 30-minute conversation with me with some references.

Lisa: I know, I know. Dr Alex, final word over to you.

Dr Alex: Well, I'm very happy we had this podcast. And that we can deliver the message that there is actually rapid scientific development — or development of medicine, experimental medicine — that is scientifically substantiated. So there are more and more options to achieve great things. But sometimes they require deep knowledge of biology and medicine to have the vision of where it's leading to. But the perspective is amazing and people, I think, soon will get more and more access to life-changing therapies.

Lisa: I hope so. I desperately hope so. Because it's already there. We could be saving lives. We could be changing lives, improving lives, and that's what we're all about. So thank you gentlemen for being on the show today. I really appreciate it. I'm going to have you both back on if I can to dive deeper into specific topics because I think we've only touched the surface on some of it. But thank you so much for your time today. You're both absolutely wonderful.

Dr Alex: Thank you, Lisa.

Dr Dave: Thank you, Lisa. Thank you, Dave.