[00:00] Hi everyone, welcome to Fawzi's Biotech and Health Extension group. [00:03] I'm really excited to finally have Ivelin Bishop here today with us. [00:07] We've been in contact with you for years now, on and off, we've been trying to schedule something. [00:12] We're really excited about your work and you've been definitely really wrapping it up over the past few years. [00:17] So I think it's a really great time to have you on. [00:19] Today you will be discussing in the group about healthy longevity medicine in the clinical practice, [00:26] which is definitely a topic that I think has become rather of interest lately. [00:31] So I'm really excited for the Q&A afterwards. [00:34] I'm sure people have lots of questions and comments and contributing similar efforts. [00:38] So without further ado, thank you so so much for joining. [00:41] I'll share a lot more about you in the chat, but for now, please take it away. [00:44] I'm very excited to have you. [00:46] Thank you so much. It's a great honor and pleasure to be here and I'm great for this opportunity. [00:51] And really congratulations to the Forsyth Institute to do it and to do it on such a scale. [00:58] I will share my slides and of course, very much looking forward to the Q&A session, [01:04] which is usually much more engaging and valuable. [01:08] When I was choosing that topic, I tried to be a little bit broader because I would like to not only discuss, [01:13] you know, whatever people already discussed in terms of the clinicians and in terms of what we want to do with health, [01:19] span versus lifespan versus the theory for the clinic that we know. [01:24] I just really wanted to talk a little bit about practical examples of what is already being done across the globe [01:31] and then really to say what is planned as in agenda by specific societies or groups. [01:39] So I would nevertheless love to start with an announcement and warm invitation to the ERDD conference. [01:47] This year, it's the 11th time that it will take place in Copenhagen. [01:52] It's, I guess, by now one of the largest aging and longevity conferences. [01:57] And since COVID, basically, we also have an integrated time specific slot for longevity medicine session. [02:06] It grew from a workshop to half a day to last year, a full day, the opening day. [02:12] And this year it expands further and it will be a whole longevity medicine track. [02:17] So it will be the full first day. [02:19] And on top of that, also other tracks along the entire conference. [02:24] Longevity medicine track will really accommodate for the clinical part and allow not only clinical discussion, [02:30] clinical trial discussions and really have a platform for doctors and healthcare professionals and affiliates to discuss various topics. [02:40] And usually we also have a co-moderator that graciously allows us to co-host the day. [02:47] Last year it was Michael Baxson from Nature Medicine. [02:50] Before that was Nature Aging. [02:51] Before that was National Health Longevity. [02:53] This year it will be revealed a little bit later. [02:55] But one thing I can already reveal is that this year conference will be also co-organized, more or less, [03:03] or will be also done partially in partnership with Express HealthSpan. [03:08] And especially with Jamie, where we are structuring the first day of Longevity Medicine Day, [03:14] a little bit together to be more aligned with hand in hand, [03:17] since Express HealthSpan is really focusing on how can we do something for the patient [03:23] and how can you bring the research to the clinic. [03:27] So this will be also the time where the endpoints will be announced and the guidelines of the prize. [03:35] And another that I want to mention that I usually always mention in my presentation, [03:39] but here I would also like to make a few announcements. [03:42] And whoever is interested to join and collaborate, everybody is always welcome, is the Longevity Education Hub. [03:49] So talking about HealthSpan, healthy longevity medicine, whatever we want to do, [03:54] I think the first step is always education of physicians, education of healthcare professionals and others. [04:00] But myself, I only know medicine. [04:03] So I was focusing on the education of the doctors and we created Longevity Education Hub, [04:09] which is offering free courses that are CME accredited by the AAMCA for introduction and then also expanded course. [04:20] And doctors who pass the quiz over 80% can also get the CME accreditation. [04:25] And still, now for the past four years, [04:28] we have been accessing still the only course that CME accredited globally for longevity medicine, [04:33] which is a very nice thing because we went to build national chapters. [04:38] And I think we have right now about 10 chapters covering 80% of the globe, [04:42] both Spanish with Chinese with Arabic courses. [04:46] And the thing that really was in our long term vision, which is starting right now, [04:51] is to bring this curriculum into men's schools and also into all residences and fellowships, [04:57] so really the last part, the practical part of the education of the doctors before they become specialists. [05:04] So that we can really advance the field and bring more clinicians into the field. [05:10] And the dream is really to have medical students finish in med school knowing what is really longevity, [05:16] knowing the mechanisms of aging and not to learn them as they go and mostly they have no time to learn it later. [05:23] So those two big announcements before I move on and usually I always start with this slide [05:30] because for me until it changes, it always reflects longevity medicine. [05:34] So I started from Alice in Wonderland, so they are running with the Red Queen. [05:39] And after running very fast, they stop and they are in the same place. [05:42] And, you know, Alice is asking why are we in the same place and the Queen is saying [05:46] that she won't actually advance, she has to run double as fast. [05:49] And that's pretty much what healthy longevity is for me. [05:52] So we are constantly running because there is just so much knowledge from neuroscience, from AI, from computing. [05:58] Now with generative AI, we're really becoming a mainstream. [06:01] And at the same time, we really also want to advance. [06:04] So that's a full-time job and a little bit more since, again, we do not have healthy longevity medicine yet as a separate discipline. [06:13] So those who actually practice it usually have also another foot somewhere else in their own home disciplines. [06:22] Or they do this, but then it's very difficult to integrate it into the typical healthcare setting that we have right now, [06:31] the healthcare systems. [06:33] And that's a little bit of a problem because it then remains something relatively closed. [06:39] But before we go into that, I would just like to mention how the definition of healthy longevity medicine [06:45] or longevity medicine has been evolving. [06:48] And it basically started a little bit in the year 2021 with the publication in Nature Aging [06:53] based on the ERDD presentation of Dr. Kai Fuli saying that longevity medicine is basically [07:00] AI-based precision medicine focusing on the health span and the lifespan. [07:04] It was pretty much the first time that somebody said it and published it in this way. [07:10] So it's not only the lifespan, primarily the health span. [07:13] And this is powered by AI technology. [07:16] Here we meant mostly the biological aging clock. [07:19] The definition has been transformed a little bit when healthy longevity medicine society was found. [07:27] Some of you might know it. [07:28] It is a society that is actually creating a platform to further bring longevity medicine [07:36] into the field as a sub-discipline, probably first a sub-discipline under internal medicine, [07:43] which also of course includes family medicine and then to hopefully also separate disciplinary [07:51] or net. [07:51] Definitely it has to be positioned as something where the doctors can be certified, [07:56] can be educated, certified, qualified properly, and also have the way to have the so-called [08:02] continuous, continued education to always be on top of their knowledge. [08:07] And this society, when we first came together in the executive committee, [08:12] we were thinking long time and discussing brainstorming and came up with the definition [08:18] that healthy longevity medicine, actually this healthy came on top of longevity medicine as we [08:23] were talking to really distinct ourselves a little bit from what longevity medicine [08:28] partially became along the years. [08:31] And instead, the definition will be optimizing health span along the lifespan by targeting [08:38] age-related processes. [08:39] So really, including the fact that we are working on age-related processes rather than [08:47] on aged populations, of course we learned from them a lot, but it's not only the thing and [08:54] it's a health span target across the entire lifespan. [08:58] That's the committee. [09:00] Here I just wanted to mention that many familiar faces, but one face might not be so familiar, [09:06] Professor Harold Pimpus, who is a psychiatrist. [09:08] He's the head of Psych at Columbia and Presbyterian. [09:11] And this is just to say that in healthy longevity medicine very often, we don't forget and we [09:18] will always keep in mind that brain cognition and also mental health is very important, [09:24] but actually to practically have that integrated into a healthy longevity medicine society, [09:29] I found that very important and I was very happy that this happened. [09:35] Now, as we are talking about bringing health and longevity medicine into the mainstream [09:40] healthcare, into something that can really be practiced, we need several things. [09:46] Of course, it's a puzzle, but we have to start somewhere. [09:49] And we started with a bunch of white papers. [09:52] Actually, our most recent paper was out a week ago or something. [09:57] It's called Building Longevity Departments in Public Clinical Settings. [10:03] You can look it up in Geoscience, which is actually telling about how did we, as the [10:09] working group of HLMS, which is constituted of Mayo and US and Sheba Israel, how we came [10:18] towards building longevity departments in public settings from building the team to [10:24] educating healthcare professionals to finding the budgets, to finding the right diagnostics, [10:29] of course, and to also interventions that are already being done for those patients [10:34] who are coming to the departments in the public setting. [10:38] But then also we will hopefully very soon have a paper on the actual definition [10:42] of longevity medicine and then for the white people to be coming now. [10:48] Of course, we immediately jumped on education. [10:52] Since the beginning of August 2022, we already had our monthly case discussions in HLMS where [11:01] not only medical doctors, but healthcare professionals and affiliates were able to [11:07] really discuss cases. [11:08] We didn't want to call it case presentations because we all do not have yet binding guidelines [11:15] and recommendations for healthy longevity medicine as in clinical setting. [11:20] But it was important for us to have a platform to discuss among those who actually practice it [11:26] or who are planning to practice. [11:29] That is still happening. [11:30] But a very important overarching goal is really to create guidelines for longevity medicine [11:38] and quality controls for doctors and for clinics. [11:43] Have a set of as it is done for any other discipline and as it is done in any other [11:48] setting where clinics and doctors have to be undergoing quality control or ongoing [11:54] pain sick and also where a discipline has a set of clear guidelines. [11:59] This is something that we want to achieve. [12:01] This has to start first with building guidelines and how to build guidelines for longevity [12:06] medicine, which is very different than in any other discipline that is focusing on sick care. [12:13] Not only because of the ICD coding that is very different and focused on pathologies, [12:18] of course, but also because at this very moment there is just not enough evidence in clinical [12:25] trials and many things. [12:26] One would say then how can you build guidelines? [12:28] Well, we would start, of course, as always with the lowest level of guidance, which are [12:33] recommendations, just three or C, whoever wants to call it which way, and then to build [12:39] it up towards guidelines. [12:41] Guidelines, both in interventions and in diagnostics. [12:45] Of course, we have to start to diagnostics because the most important thing right now [12:50] for the success of clinical trials is the definition of the right end points and those [12:57] are the biomarkers of aging. [12:59] Luckily, within the last almost two years now we have consortium of aging biomarkers, [13:06] both the aging biomarker consortium in the US but also big biomarker consortium in China [13:13] and both of them are doing a great job to build it up. [13:17] Here just to show once again where are in the world already longevity, I like to say [13:23] longevity departments. [13:24] One might say longevity centers where people can come and undergo some level of longevity [13:32] diagnostics for our center here in Shiba. [13:36] It's fully for free and we will have this year 1,500 people who will undergo 360 screening [13:43] for longevity at baseline six months and then 12 months. [13:47] All of those people would be in the study. [13:49] 80% would be randomizing to interventions and would be given or are given interventions [13:55] for a year to come and then there will be a crossover. [13:58] On the one hand, that's already a service for people coming from across the country [14:04] to be screened but at the same time, of course, the end points which will include the biomarkers [14:09] but also compliance will hopefully be something that can be presented to health insurances [14:18] to say it actually makes sense by the economical calculation to implement some sort of program [14:24] in the packages and to have people giving the accessibility to such longevity services. [14:33] Overall, of course, it's an ongoing learning and as we are learning and translating healthy [14:38] longevity medicine, I think almost every month we are adding something new into the center, [14:43] being from a new technology for diagnostics to some new flocks that are out there, [14:48] new signatures for methylation. That's extremely fun to do and beautiful but at the same time, [14:55] really this tertiary digital layer of the patient expands. It's a lot of data. [15:00] It's a huge amount of data and it's a data lake that is hard to handle in clinics that are [15:07] primed for significant care that have been in the system for years and decades and more. [15:12] And so the EHR really has to expand in a way that only a center that is really open-minded can do, [15:22] which is very interesting. And of course, without AI, it's impossible. So it's very important once [15:31] a center has decided to be a longevity center and be at a scale that goes into thousands rather than [15:39] hundreds. It's very important to have besides the strong IT in the background, besides the strong [15:46] data lake capacity in the background, also an AI arm that can fuel in all this information [15:53] continuously and hopefully be connected to something that is teaching a very large LLM. [16:00] So large language models, I think, in health and longevity medicine as we speak are being trained. [16:05] AI is learning constantly. There are big transformers being conducted and done. [16:11] Some of the publications are already even available. I will show them in a moment. [16:17] And one has to think about that as a doctor who is creating such a or running such a department [16:22] to have this in the background. So what one can see on the surface, all the testings, all the center, [16:29] equipment, all the doctors who are there as they usually would be. The power is in the [16:35] backside. The power is in the AI that is behind it. And I think we are seeing really a constant [16:43] revolution of what the field is. So when we tried to do a timeline, we saw there was quite a fast [16:52] progress in general up until the year 2015. We had the Hallmarks of Aging, the Seminar [16:59] publication, we had the Harvard Clock, which was for me personally a huge revolution. I remember [17:05] learning at the med school and it really transformed and shifted our minds of doctors from telomeres. [17:12] There might be something more in terms of aging. There's something more that controls it. And there [17:17] was also CRISP coming up. Then really the biggest point came, I think, in the year 2015, [17:23] where we started to see more and more AI in medicine and all the comics revolution came on. [17:29] And then also deep aging clocks were coming. And this is thanks to the fact that around this time, [17:35] the deep neural networks were developed and really applied in order to really have the data [17:42] analyzed first structured and then analyzed in a way that would bring a sanctionable objective out [17:49] this something that is usable, such as biological age. And then the wearables came. So [17:58] healthy longevity medicine without wearables and very good integration of those wearables [18:04] in the API and daily use is impossible. So it's very important to use it. [18:11] And then the clinical trials and supplements came and more and more. Until now, even as I mentioned, [18:18] we have large-handwich models, we have transformers that are being built. And that's something that I'm [18:24] extremely excited about. Actually, healthy longevity medicine has been using generative [18:28] AI for a long time. It was just not as accessible to people until CHEP GPT came out. But it was [18:37] already being announced and everything that's generative AI was allowing us to use was already [18:42] being applied in order to, as I mentioned before, be able to integrate structure and analyze the [18:51] at large scale longitudinally, but also data that is really extremely heterogeneous and multimodal. [18:59] Because for healthy longevity medicine, we have to go from the omics to the systems, [19:03] through the organs, neptests, radiomics, actually at this point of time, historical records, [19:10] very deep anonymistic records, and so on. Up until the point that we also tried to [19:17] get as much data points as possible from the epigenetics. So from the environment, [19:21] the influences on the person themselves that actually changed the epigenome. And that was only [19:28] possible with the learning methods that allowed us to get some sort of objective function out of [19:35] it. The objective function mostly was personalized medicine, advice, recommendation, and right now, [19:41] much more, for example, AI based drugs, which we'll talk about just in a moment. [19:47] Now, as I mentioned, deep neural networks were tremendously important for that to happen, but [19:56] also other versions of learning. There are good sources to learn about that there's actually a [20:02] chapter in the book called AI and longevity medicine that is talking much more deeper about [20:08] federal learning and transfer learning that were used in order to get what you call today biological [20:15] aging clocks, but also other personalized recommendations. And as I mentioned before, [20:21] generative AI and longevity medicine has been used already before really to integrate all the [20:26] sets from those very different data points, extremely heterogeneous through the neural networks [20:32] into something that is actionable for a clinic. For example, what is the aging pathway that is being [20:37] targeted? What are the synthetic data out of it? What are the potential trackable targets? How to [20:44] build a track out of this information? So that was already happening. Now going out of the deep AI, [20:54] how does it translate to an actual practice? What can we do? And how is longevity medicine [21:00] different from prevention? How is it different or how does it fit into also our reactive medicine [21:08] reality? So I don't claim that this is the right way to see it. For me, it just helps to see it [21:15] this way that first we have reactive medicine and it will not disappear for seenables. We treat [21:21] diseases, we react to a disease and that's important and basically any doctor has to know [21:27] how to do that. Then there is prevention, prevention from primary to tertiary prevention. [21:32] It's a proactive approach, we detect early diseases. So therefore the disease is already there or [21:37] early recurrence, right? But there is already a pathology that we detect and we detect early [21:42] in order to remove and treat that pathology. So that's also great and that's very well established [21:46] there are clear guidelines and that's very important. Now what's different in healthy [21:50] longevity medicine? Depending on the scale how it's being done, it can encompass also prevention [21:56] or be an additional part to prevention. I think both are totally okay. And for example, for us, [22:03] we separate, right? We have a specific order center that is doing prevention with all the screenings, [22:09] with colonoscopies, mammographies and others. And we do the extras, right? From the functional [22:14] testing to the methylation to biological age and so on. But there are centers that integrate both, [22:21] also fine, that goes hand in hand, but it's so different. And in this part, really longevity [22:28] medicine is about detecting the risk of developing a disease and trying to assess the gravity or the [22:35] dimension of that specific risk for a specific patient and bring the patient from current status [22:42] of different markers to the optimal status of those markers in order to optimize the health [22:49] span. And I'm probably repeating myself and I'm talking to the experts here, but nevertheless, [22:54] I think it has to be said, we are extending our life expectancy tremendously fast and it has [23:01] expanded in the past hundred years, but the health span didn't extend at the same speed and therefore [23:07] we have the gap. And so healthy longevity medicine is really trying to close that gap. [23:13] And so primarily it's really not about further extending the lifespan. For some people, it is, [23:18] you know, by product that is desirable, which is great, that's the desire, but it's really about [23:25] closing the gap of health span and lifespan and extending the healthy years of life. So basically [23:33] age and disease or death with good health. And because the definition is optimizing health span [23:44] along with lifespan, we are talking about also really optimizing a point of life that we could [23:53] call a peak performance or peak individual performance. Basically in normal real world [24:00] scenario in medicine and beyond, we would look at patient's chronological age along the lifespan [24:07] of a patient and we would see that the patient is going, you know, to a curve of life. I'm sure you've [24:13] seen that before in different places that's actually taken from the Nature Aging publication. [24:18] So we basically see a patient who is, you know, being born and until the adolescent is being [24:24] usually guided by one or two doctors, neonatologists, pediatricians, and we all know [24:31] the norms. So everything is very normative. There are ranges by chronological age. A child has to [24:37] achieve this and this and that within a specific age. That's basically how it's being done. [24:43] Until the person is reaching this level, which is that peak individual performance, this is usually [24:49] a short interval of our life where we have the top functionality of our body and mind. [24:55] And from that moment on, it's a functional decline at different pace for different people. [25:02] And usually this is also where different doctors are evaluating the person within norms that are [25:10] mostly based on chronological age, but not only, but these are the norms. We have the normative [25:15] values and they are, you know, we usually in the clinic, we love what's outside the norm, [25:20] what's within the norm. And then we try to act if needed or if possible. And that's pretty much it. [25:29] Of course there are limitations because doctors' memory is extremely limited and there is a [25:33] dispersion. You know, if there's two or three doctors looking at the case, there will always be [25:39] a problem to bring everybody together at the same point. So there is a lot of information that is [25:46] leaking and usually that leaked information is not beneficial for the patient outcome. So the decline [25:52] is going towards very often a very comorbid or multi-morbid end of life. [25:59] Now in health and longevity medicine, as you can see, it's not a tremendously extended lifespan [26:06] here. So the length of life, the years of life might say the same or maybe a little longer, [26:11] again, buying product. What we are really trying to focus here is to have the patient being as [26:17] close as possible to patient's personal, individual peak performance. So how we do that? We are trying [26:28] our best to develop and to use biological aging clocks and really to evaluate the patient with [26:34] algorithms that are trying to tell us not only how old the patient is biologically at a specific [26:40] point of time, but also what would be the optimal biological age of that patient at that specific [26:48] point of time and which parameters need to be fixed in order to bring that patient back. [26:56] And for this, of course, we are mostly using longitudinal data. I usually tell patients [27:02] I usually tell patients, please do share with me anything that you have from your old data, [27:08] simply because the more the better and the more longitudinal in the past those data points are, [27:16] the better the predictions of what can be optimized. And so therefore, longevity medicine [27:23] is really standing on two pillars in my opinion. We have the diagnostics and we have the interventions [27:29] Luckily right now, the intervention part is growing more and more. A few years ago, [27:33] it was primarily diagnostics and there was a lot of criticism saying, why do we do all this? [27:39] We have nothing that we can really do about it. And the answer was if we don't test [27:46] with this new longevity diagnostic precision medicine, and if we don't fuel it into the [27:51] algorithm, we will never be able to find, identify the right endpoints, the right biomarkers for [27:58] clinical trials. And this is exactly what was happening in the past years. And this is why [28:05] luckily we see more and more of those endpoints and biomarkers being validated and therefore useful [28:13] for clinical trials. So finally, we can test which supplements are beneficial for extension [28:18] of health plan and which are not and also repurposed drugs and also hope to be very soon new [28:23] components, both analytics and your protectors and also technologies, right? And to check if [28:31] they are beneficial or not. So what is happening are mostly now as I'm showing now, the longevity [28:37] diagnostic centers, we have a whole fan again, going from either only longevity diagnostics or [28:45] preventative and longevity diagnostics ranging from pulled by the MRIs with overlay AI algorithm [28:54] through other radiomics, through functional tests, through labs, very extensive lab, [29:00] and also through wearables and also through more and more liquid biopsies and of course, [29:06] omics and microbiome. So microbiomics one could say, and hopefully very soon, [29:12] a much bigger panel on biological aging clocks. And what already was established and is now being [29:20] even more important and useful in the clinical practice is the polygenic risk score. So really [29:26] having the mosaic of the genes and saying, not only do you have this and this pathological [29:33] mutation or you're a carrier of this and this disease, which is important, which is good to [29:37] have a WGS, but also the polygenic risk score really to see the mosaic of where is the patient [29:43] standing in terms of risk to develop a disease at a specific point of time that is really correlated [29:51] to mortality. So CVS and dementia and their own, so not only cancer and pharmacogenomics. Luckily, [29:59] it's really becoming a mainstream and most clinics I've been working with, public setting also have [30:06] pharmacogenomics being done at least once and where we are guiding our treatment, [30:12] if a treatment is needed with the help of pharmacogenomics. [30:17] And last but not least, of course, wearables. I personally am a big fan of those. I think it's a [30:22] great tool for feedback, but also for the doctor to have the chance to have an instant glimpse of [30:29] continuous monitoring. And besides of the things that we all know from the wearable [30:35] CGNs, all the bands of the rings for the high HRE and all the other vital signs, [30:42] I think we are all more and more excited also to have the continuous cholesterol monitors being [30:48] improved and validated, mini polysomnographies in from even of a ring for the night that are giving [30:55] us quite valuable data for the sleep apnea and movement. And last but not least, really a very [31:01] good monitoring of our liquids as in liquid biopsies. So really not only checking in the blood [31:09] for pan cancer panels or cancer panels, CTDNAs or RNAs or CTCs, so circulating tumor cells, [31:18] but more and more in liquids or other samples such as stool, such as urine. Stool is very [31:24] established already with the PoloGuard, but not many people know that there are urine tests that [31:29] are testing for prostate and bladder cancer. And hopefully we'll have more and more of those types [31:34] of fluids that can be tested. And of course, also breath, so volatile particles that are also [31:39] predictive of cancer from lung to other endocrine cancers. So I think those things are extremely [31:46] valuable because all of those data points, if they can be integrated properly, will give us [31:54] really a patient's digital twin and help us to understand which of the levels of aging for a [32:01] specific patient are accelerated. Is it the molecular level, the cell level, tissue, organ system? [32:08] Is the epigenetic not really fitted for the patient, the influence of the environment? And [32:14] at the same time, which really of the function, so the functionalities, which of the functionalities [32:20] for the patient clinically is decreasing? Is it the vital capacity? Is it really the only [32:25] oligofactory system? Which of the system and the organs and functions altogether are decreasing [32:31] for a patient specifically? This allows not only to know, but also to optimize the longevity [32:39] diagnostic and monitoring protocol. And as you can see here, it has to be granular and has to be [32:45] individualized. And some things extend from something that has to be done daily continuously [32:52] and to points that can be done once in a lifetime, such as whole genome sequencing, and then just to [32:58] recheck for new mutations as our knowledge of genes is growing. But at the same time, [33:05] this type of protocol is not only about do those tests, take those pills. It's a whole package of [33:13] a longevity protocol, which also is very important. The education of the patient [33:18] is a longevity program ready to strategically tell the patient not only sleep well, eat well, move, [33:25] but to strategically say, you have to do this exercise so and so many times for so and so many [33:31] minutes with this and this rate, with this and this time to rest to achieve this and that specific [33:38] outcome for your caliper or your group strength or whatsoever this is. So really going very granular [33:45] and individual for the patient's specific needs. Of course, we have a great help now with the [33:52] biological aging clocks and we have a whole variety of those and they are expanding and then it's just [33:57] so wonderful to see. By far, what I'm showing here is not everything that we have. And this is just an [34:04] example of the deep aging clocks, but very valuable to see that the variety that is out there [34:11] and all the different people who are developing those, there is a very collaborative spirit [34:16] because we will need to know which clock is actually measuring what. Besides of the fact to [34:22] know that, oh, this is my biological age, every doctor and hopefully also the patient will [34:27] understand what this actually means for me. Why is my epigenetic clock showing me minus 20 years, [34:31] but my blood clock is showing me plus five? Where's the problem? How does it differ? How [34:36] do they measure those values? I think it's very important to understand, okay, this algorithm is [34:42] behind and epigenetic clocks are measuring your age, but they are oscillating around an axis [34:50] and the blood clock, for example, is really based on those 45s and blood markers and it is [34:58] predictive for mortality, but hey, maybe morbidity is different and other factors were not included. [35:05] And then at some point in time, once hopefully we will have a much thicker data set that will [35:10] be also shared between each other, we will be able to understand what are the inter-functions [35:16] and intersections and influences between each other between those biological aging clocks. [35:21] On top of that, it will be very important to have specific organ clocks and organ [35:27] clocks that are working on data sets that are maybe not mainstream. So clocks based on [35:32] epidemics, clocks based only on specific function of the heart, but on the structure, [35:38] not only on the functionality like HRV. Those are the things that are all in a pipeline, [35:43] not validated, but ongoing. And I think that it's very important for us in the clinic to embrace them [35:50] in order really to validate. And what is also extremely important and growing, I think, [35:56] is the focus on a microbiome. So I just wanted to mention that there are already [36:03] efforts to, and there are already clocks out there that are based on microbiome and there [36:08] are efforts to extend those and the new, which is I think extremely important, microbiome plays [36:14] a tremendously important role, but also clocks that are very much focusing on reproductive health [36:22] in the productive age and then later menopause, and repulse, especially, I see Aaron is here [36:29] and very focused on menopause and extremely focused on under pulse. And I think once we know more, [36:35] once we really understand longitudinally which hormones are changing, how can we actually measure [36:40] the reproductive biological age or have a menopause at clock, we can do a lot more than just HRT, [36:47] hormone replacement therapy. And then as I mentioned also before, how can we really see [36:53] the interactions and the proportions and interchanges of those different clocks [37:02] between each other? That's very important. And how it usually looks like, for example, [37:07] for the blood age like this, most of you probably have seen it, maybe some not, [37:12] we usually after fueling in the algorithm, we get an output report and such a report is [37:19] giving us a chronological age and then the biological age. So this was actually a patient [37:24] young male, 41, biologically 45, without really many of the factors that were extremely out of [37:32] the norm. So in a normative setting, we'll say, okay, your cholesterol is a bit elevated, 200 is [37:38] norm, or anything below is good, your is 205, whatever. But as you can see here, it's really [37:43] about the optimal values. So the norm values are being left out in that sense and the optimal [37:52] values for that specific patient at this specific point of time is being listed. And those that are [37:57] influenceable can be then modified with the help of doctor to reduce or increase those. And what [38:05] was very useful is the fact that we can repeat those tests, not every week, not every month, [38:12] but it's reasonable to repeat them like every three months. If you want to really intervene [38:16] and have somebody have a change and do something, we have the longitudinal follow up. And this was [38:23] a patient who was actually in August, 38 biologically, and then it increased to 44, [38:30] literally within half a year. And what happened here, the patient started to actually take quite [38:35] a bit of supplements. Oh, we might mention which ones, but let's say the dose was triple as high [38:40] as what would usually be recommended on the supplements, thinking that more is better, [38:45] but actually very often in medicine we say less is more. So this patient's injury listens, [38:51] he didn't want to stop the supplements, he continued. And after we measured like another [38:55] half a year later, he went up and then he started to listen and to reduce and two things [39:00] to stop. And then the biological age actually went down. That was very good. But it's really [39:06] a work one-on-one with the patient and it is scalable as we can see already with the public [39:13] departments. It's scalable. It's of course less general, but it's scalable. And it's all about [39:20] guide the right guidance where the continuous monitoring is very helpful, more detailed [39:27] diagnostic on a larger scale and really also finding the right medication and or supplements [39:32] for the patient in specific intervals. Now, therefore we can follow up. [39:40] I know that we have about 13 minutes left. Oh, okay. Thank you for that. We were chatting in [39:47] upfront to make sure that I'm not going over time, which I'm apologizing for. I usually I do. [39:52] So we can really longitudinal follow up the patient and see biologically where the patient [39:57] is standing. And there are also a few special cases for those who are interested. Sometimes we see [40:03] a patient, this is just an example of a patient who was chronologically 29th, a female had a [40:09] problem to get pregnant for no really apparent reasons. Hormones were okay. Everything was fine. [40:15] Structurally, gynecologically everything was fine. No children. So when we measure the biological [40:20] age, I just said, you know, out of let's just do it. Let's see what's going on. And she went [40:24] biologically 31. You might say the Delta is not very big, but actually for a patient at this age [40:29] for that specific algorithm, it's a lot. And we know that patients who are being getting a Delta [40:37] that is higher very often and they do not have apparent blood parameters that make them older. [40:44] So everything is within the norm, very often have autoimmune diseases. And indeed for that [40:49] patient was the case actually, it was more of a beginner. So clearly she was, you know, she had [40:54] great difficulty to get a child. So again, see things can be detected more than just, you know, [41:01] saying this is suboptimal and you can improve. And maybe just for the closure, things that are [41:09] really passionate, that they're very passionate about. And I think that this will re-advance the [41:15] field is AI based drug discovery without making promotion for Ensilico, but they are the leaders [41:21] you might have seen the nature biotech paper that just came out two weeks ago about the first [41:26] drug that was AI discovered and is now in phase 2B within like less under 18 months, which usually [41:34] takes years and billions. Anyways, so this AI based drugs are very interesting because, because [41:41] they are using so much data power, they can actually not only focus on the disease, [41:48] but they also can integrate another function. So they have like a dual target. They can target [41:55] a specific disease, a gene or, you know, some kindness, some enzyme, but on top of that, [42:00] do something else. So for example, the drug that was mentioned there is a drug pro-fibrosis [42:06] developed for IPA, you know, idiopathic pulmonic fibrosis, very deadly, a horrible disease where [42:12] there is no cure. We can only manage it and put it into a chronic state. This drug is actually [42:19] reversing, but it's also reversing fibrosis, which is one of the main side effects of aging. [42:25] So that is very interesting. And again, it's extremely scalable because what is happening is [42:29] huge AI robotic labs, which have zero people in it, only the robot, they can be miniaturized [42:37] and placed in the hospitals. So me as a doctor, if I have my patients, I also work as an oncologist. [42:43] So if I have my patient and they can take a tissue and I can just send it to the robot, [42:47] that will do the high output analysis and fuel it into a database that is connected all over the [42:53] world. With my patients, I might find number one, old targets and find the right medicine for my [42:59] patient, which is a very easy thing right now to do. But secondly, maybe I can find a new target [43:05] and somebody else had this target as well and we can potentially create a new drug that can we use. [43:13] So again, how can we bridge the sick care and the new wave of healthy longevity medicine [43:21] by actually doing? As I mentioned before, we already had a healthy longevity department in [43:27] several hospitals, but at the same time, there are also hospitals that are 100% sick care hospitals [43:34] and it's the one that they're working, for example, in China that is transforming on a little bit of [43:39] a different level because the amount of people is much higher. And what we are doing there is [43:46] basically building a sort of smart hospital because integration of data in that specific setting [43:53] is the most important across the globe. With this, I'm going to finish up thanking you for your [44:01] attention and very open for any questions and discussion. Thank you so much. You cover a really [44:10] wide range there. That's really helpful and congrats on all of these efforts. I don't know [44:14] how you possibly could have time for all of this. Thank you. Okay, we have Karl here with his first [44:21] question. I was waiting for quite some time and if you want to drop your questions in the chat, [44:25] you're welcome to do so or feel free to raise your hand at this point as well. [44:29] Very expansive, impressive effort. Obviously, the world needs better education of all the positions [44:36] on things that are going on in the field that we know and love. So my question is about [44:41] standard of care. You talked a lot about expansion and diagnostics and stuff, but [44:48] Nala, and I've heard lots of stuff about the whole effort from you and from Andrea, but I hardly ever [44:54] hear anything about what the actual advice and standard of care being advocated is. What are we [45:03] teaching? Who's deciding on what standard of care for longevity medicine is? And I think [45:11] that's one of the things that we've been talking about for a long time is we want it to be more [45:17] than what normal doctors are trained on. And there are some consensus from the aging research field, [45:24] but there's also a lot of controversies and things that we don't know. And yet, individual [45:28] doctors are making their own recommendations in some of these areas. So how is the society deciding [45:35] and advocate as standard of care in this area? Is there a plan for, especially for the controversial [45:41] things where researchers disagree? And is there a plan for some kind of broader global conversation [45:47] to decide on what it should be in the areas as we get more data? Or is that something that you [45:53] and the other leaders of the movement see as more appropriate to happen behind closed doors? [45:59] I hear you. And answer to your last question for sure, no. And I also don't think a society [46:06] can or is in place to decide anything. At this very moment, I think the society can only facilitate [46:13] the effort to bring whatever is out there proposed as potential standard of care to higher councils [46:21] and discuss with them what potentially can be done. But since this will take a long time, [46:27] therefore, many of you might have heard and we also among our members and broadly we said we want [46:34] to create the working group about the guidelines, but it's not something that will happen immediately [46:39] and nobody in my personal opinion here is in a position to say this is the standard of care. [46:45] One can recommend and this is why I mentioned at the beginning that guidelines have to start [46:51] with guidelines, how to build guidelines in this field. And this can be only done with [46:57] test scores with close collaboration with the councils that have been done doing this for other [47:03] disciplines for decades. And then only after that can recommendations come as recommendations, [47:10] the lowest level of evidence and from that guidance. For me, that will take years. Therefore, [47:16] I think and definitely nothing should be happening in any field in my opinion behind closed doors. [47:22] But on top of that, I think we also need to do things already on maximum credible level. [47:30] The public setting, for example, here, of course, we understand that using some of the biological [47:35] aging clocks might not be in the standard evidence base, but we will. So that's why we do it as a [47:41] study, right? Every patient who is coming to the center is also a part of a study. And I guess [47:48] that's very important and we'll be showing what later will be the recommendations in the guidelines. [47:55] Thanks. [47:56] Oh, we have Larry. [47:59] Yeah, hi. I think it was a great presentation. And I think for patients who can [48:04] undergo the type of individualized therapy you're recommending, it could be beneficial. [48:10] The problem is, that was touched on just recently, is coordination of clinical trials, [48:18] coordination of clinical information. That was the huge problem with COVID is that there are all [48:23] kinds of clinical trials started, but no information came out of them. And I think in longevity, [48:28] that's a little bit where they're at now. There's a lot of things going on. There isn't [48:33] much coordination of effort. I heard Ray Curzell was on a podcast. He's taking 80 pills. I don't [48:41] know, maybe some of them are helping him, maybe some aren't, but there's a lot of this stuff [48:44] going forward already without very little evidence behind it. Vitamin D, there's some evidence that [48:51] prevents cancer. There's also evidence that it might cause heart problems. A lot of these things [48:57] to really get the real answer for which people they'll be beneficial for, it's a bit complicated, [49:04] but if you don't coordinate studies, we're just going to be at the same place we are 10 years from [49:10] now when people are taking all kinds of things and nobody knows what really works. And there's all [49:15] kinds of biomarkers out there and some are contradictory to each other as well. And I think [49:21] the important thing are simple studies that improve people's lives. And I don't know if you [49:26] need the depth of study that you're doing for that. So first of all, thanks for mentioning many [49:32] aspects. And I guess, again, I can speak for me personally, but I know that many people share it [49:37] and I'm actually going to quote Dr. Cran here, coordination and collaboration, I think, is [49:42] tremendously important. Most of the clinical trials that are running in oncology, for example, [49:47] are not exactly coordinated in a way that everybody will need to report to everybody [49:52] how to do it. There are no massive consortia, but there is a coordination because people [49:57] talk to each other much more than we can because it's already an established discipline and there's [50:02] a little bit of a different exchange and there are guidelines that cannot be crossed paths. [50:06] We are starting something new. I like to compare this to interventional radiology, [50:11] discipline that became very successful in a very short period of time. But if you look up for [50:16] guidelines in interventional radiology, you will not find much, right? But still it's working, [50:20] it's working very well. So I think coordination is important, but without over regulation. [50:28] And at the same time, I think it's also important to exchange data more. So rather than just [50:36] coordinate, also exchange. And yes, of course, there are plenty of potential biomarkers out [50:42] there that have been published already since the last decade. I think the consortia that are out [50:47] there, which I'm a big fan of, is their role in the way to at least give us a way to validate that, [50:55] even within clinical trials. But one thing I didn't have time to talk about and which I think is a [51:00] very important key point in longevity medicine, and hopefully it will be done much more, is the N [51:07] equals one clinical trial, which is not the same as trying out and anecdotal, but really N1 [51:15] clinical trial in the setting. I think we will learn a lot from this as well. [51:21] Lila So Wonderful. We unfortunately only have one minute left. And so I always wanted to finish on [51:27] the note of if people are excited about your work and with what you work, many different efforts, [51:33] how can they learn more? How can they get in touch? Is there anything in particular [51:36] as a research collaboration or something that you're looking for that people can help with? [51:40] Lila I don't have a website or something, but I'm on LinkedIn and I'm extremely, [51:45] hopefully extremely responsive. And I always am always happy about collaborations, extremely [51:51] much so in terms of clinical trials. And if somebody's working on longevity education, [51:56] as in clinical councils, medical councils, or somebody's working on clinical trials with [52:02] repurposed drugs, with liceanalytic drug protectors, always have been very happy to collaborate [52:07] and AI. So if there are platforms that are aiming at integrating, then always also very welcome. [52:16] And in general, always happy to connect. Lila Wonderful. Thank you so much. I'm [52:21] really happy that we finally got to work. Thanks a lot for taking some time out of [52:24] your really busy schedule. Lila Thank you so much for having me. [52:27] Lila It's a great honor and pleasure. Lila Thanks everyone for joining and for [52:31] your great questions. And I hope to see you all very soon. Have a wonderful rest of your day. Bye, everyone.