AKG Open Enrollment Longevity Group Orientation (Longevity Connect – March 2024)

On March 21, 2024, the Clock Foundation team hosted another Longevity Connect webinar. This session focused on exploring the Open Enrollment Groups Initiative and our initial cohort attempting to validate anti-aging effects of AKG. Head of Product Mark Koester demo-ed the usage of the Longevity Tracker portal for completing key enrollment surveys and managing your treatment plan and schedule 

Executive Director, Bobby Brooke, provided his review and summary of updates from the longevity field. He highlighted key papers, studies and findings that have emerged in the last few weeks and months as well as influencer updates including “drama” between two key longevity researchers, Matt Kaeberlein and David Sinclair.

Below is the full video presentation, full citations, summary, screenshots and transcript. 

Agenda and Table of Contents of Topics Covered

  1. 🚀Overview / Launch of AKG Testing Group, Clock Foundation’s Inaugural Longevity Group
  2. ⏰ Review of Epigenetic Clock Papers
  3. 🔬 Mechanistic study review 
  4. 🩸 Aging biomarkers review
  5. 📰 Influencer & Initiative Updates 📣
  6. 🗣️Twitter Talk

About Us

Founded by Steve Horvath and Bobby Brooke, the nonprofit Clock Foundation (https://clockfoundation.org)  is dedicated to pushing the boundaries of longevity research for tangible improvements in human health and lifespan. We’ve completed over 300 longevity projects in our first 3 years. 

Through MyAgingTests.com, we offer cutting-edge biological age testing and a range of longevity services and software solutions for individuals and groups (clinics, researchers and coaches) interested in quantifying aging and managing anti-aging programs, intervention studies and trials. 

Learn more at https://clockfoundation.org/get-started/.  

Longevity Connect is a Monthly Longevity Science and Anti-Aging Strategies Virtual Meetup, brought to you by Clock Foundation and MyAgingTests.com.

Got questions or interested in joining our next Longevity Connect event? Check our event schedule and signup at https://myagingtests.com/longevity-connect/

Watch the Full Presentation

VIDEO COMING SOON!

Disclaimer 

Disclaimer: Nearly all aging biomarker tests today are “research use only” tests, which means they are not approved by FDA for use in treatment of any diseases. There is no guarantee that even with the best measures of biological or epigenetic age, i.e. epigenetic clocks, that if you reverse it by 5 years it will always translate into 5 extra years of life.

You should always consult your physician before initiating any new treatment.

Conflicts of Interest: I (Bobby Brooke) work with a private biotech company Intervene Immune developing treatments for immune system regeneration. Through Clock Foundation I work as a non-profit collaborator for dozens of aging researchers, including many academics and longevity biotech companies.

For Longevity Connect recaps, we focus on analysis of data that’s already been published, and largely on treatments that are already available for use in clinical trials.

Key Topics: Longevity Connect on March 21, 2024

🚀Overview / Launch of AKG Testing Group, Clock Foundation’s Inaugural Longevity Group

What are Longevity Groups? 

Longevity Groups are participatory research opportunities facilitated by the Clock Foundation to explore the anti-aging effects of different agents and protocols. The central aim of the Longevity Groups initiative is to generate more reliable interventional data on supplements, medications and treatments that are commonly used or discussed for longevity but currently lack rigorous study results. 

Participant and scientific benefits include: 

  • Facilitating rapid testing of agents’ effects on epigenetic clocks and aging biomarkers through participatory research.
  • Collecting biomarker data from groups taking interventions to understand collective impacts on measures of biological age.
  • Providing individuals participating in the groups personalized reports and insights into how their biological age is changing over time.
  • Enabling comparison of different interventions’ effects through launching multiple groups testing various protocols.
  • Accelerating development of reliable treatments for aging by using biomarker data to evaluate interventions’ ability to potentially extend healthspan and lifespan.

Several group initiatives are in the pipeline. Learn more at https://myagingtests.com/open-enrollment-groups/ 

AKG Testing Group

The AKG testing group specifically aims to investigate the effects of AKG supplements on epigenetic clocks and aging biomarkers. This group represents the Foundation’s first step into evaluating the epigenetic effects through the Open Enrollment Longevity Groups initiative. By individuals taking biological age tests and following the same protocol, we hope to provide valuable and actionable insights into anti-aging interventions that work individually and collectively. 

How does it work: 

  • Participants will obtain their own AKG, follow a shared testing protocol, and share their biomarker data anonymously. 
  • This data will be used for data analysis and to generate a group report to understand how AKG collectively impacts key measures of biological age. 

Besides completing some enrolment and compliance surveys, participants must obtain one of our biological age monitoring subscriptions and take AKG for 6 months to provide robust before and after data.

Interested in participating? Sign up here or contact us at [email protected].

Monthly Longevity Research Roundup

⏰ Epigenetic Clock Papers – Clock Tech

Bobby Brooke reviewed a few recent papers on epigenetic clock technologies and data:

  • A new age predictor was developed using only 11 methylation sites that achieved high accuracy in distinguishing young vs old samples.
  • A paper looked at predicting age using cell-free DNA from plasma, also achieving prediction within a few years.
  • Single-cell methylation data is providing more sophisticated understanding of age-related changes in individual cell types.
  • Mendelian randomization studies examined relationships between epigenetic aging and diseases like aortic valve stenosis and obesity.
  • Validation studies showed epigenetic clocks like GrimAge outperform others in predicting future health risks in independent datasets and large populations.
  • There is a lack of reliable interventional data to determine if reversing epigenetic aging biomarkers can reduce disease onset, which these types of studies aim to address.

Full List of papers reviewed: 

📈 Epigenetic Clock Papers – Clock Data/Results

Validation of biomarkers of aging – Nature Medicine, Biomarkers of Aging Consortium

  • Types of validation: Biological, Cross-species, Predictive, Analytical, & Clinical
  • Gaps?

Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality

  • “GrimAge acceleration is a stronger predictor of 4-y mortality (than DunedinPACE and all others)”

Epigenetic age acceleration and risk of aortic valve stenosis: a bidirectional Mendelian randomization study

  • Symptomatic AVS is associated with 2-year mortality of more than 50%

Causal association of obesity with epigenetic aging and telomere length: a bidirectional mendelian randomization study

  • 2-way effect of epigenetic aging with obesity
  • Mendelian randomization studies looking at relationships between epigenetic aging and diseases. 

🔬🧪General Science

A New Obelisk ‘Lifeform’ Is Hiding Inside Humans

“…we surveyed Obelisks in five published human oral and gut microbiome studies from 472 donors, finding an estimated ~9.7 % donor prevalence” 

A new paper was discussed that discovered a new type of virus, called an Obelisk, that was found to be infecting the human microbiome. Researchers discovered this virus through improved sequencing technology, and it was found to be present in about 10% of the population worldwide. Remarkably, it was a virus that researchers were previously unaware of. Notable is that methylation plays a role in suppressing ancient DNA derived from viruses that have infected our genome over time. There are some drugs that suppress viruses and have been shown to improve epigenetic aging, providing tools to address newly discovered viruses like Obelisk. The discovery highlights how there is still much we are learning about factors that influence epigenetic changes like methylation patterns related to aging.

Popular Mechanic Write-up 

🔬 Mechanisms of Aging Review

Somatic mutation rates scale with lifespan across mammals

  • a conserved set of mutational processes dominate somatic mutagenesis across mammals
  • widespread clonal expansions in ageing human tissues raises the possibility that some somatic mutations contribute to ageing by driving clonal expansions of functionally altered cells
  • clonal haematopoiesis and cardiovascular disease
  • mutations in liver disease and insulin resistance
  • driver mutations in cavernomas and brain haemorrhages

🩸 Aging biomarkers review and news 👩‍⚕️

Plasma proteomic profiles predict future dementia in healthy adults

  • Dementia Predictors? A large prospective study linked several plasma proteins to future risk of Alzheimer’s. Top hits: GFAP, NfL, GDF15, and LTBP.
  • When combined with demographic data on sex, age, education, and APOE genotype, plasma GFAP predicted the onset of dementia of any type with 89 percent accuracy, the authors noted.
  • GDF15 was most highly associated with vascular dementia.

💊 Treatment News 👨🏽‍⚕️

PROMOTe: Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial

COSMOS: Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS

📰 Influencer & Initiative Updates 📣

XPRIZE Foundation – August team meeting in Copenhagen

LBF Roadmap – Nathan Cheng & Mark Hamalainen

Technical Roadmap:

  1. Replacement – tissue/organ replacement
  2. Biostatus – cryonics
  3. Advanced Bioengineering – genetic/cellular engineering

View Deck

🗣️Twitter Talk 🍿🎤

Kaeberlein & Sinclair Drama

There was some “controversy” on Twitter between two prominent aging researchers David Sinclair and Matt Kaeberlein. David Sinclair announced a new supplement that he claimed reversed aging in dogs, based on some study data. Matt Kaeberlein strongly pushed back, saying the data did not prove reversal of aging and the claims were a lie. Sinclair then changed his messaging to say it only slowed aging effects. Both researchers then resigned from an aging research group they were both previously part of.

There was debate around responsible messaging of study findings and holding researchers accountable for claims about treatments and their effects on aging. This highlighted tensions around clearly communicating data limitations and not overstating preliminary results from studies.

The definition of “Biological age”

Morgan Levine, an aging researcher, had a strong reaction to a post by a personal trainer about findings from a study. The post claimed a treatment reversed biological age by 5 years in only 8 weeks. Levine said influencers were misrepresenting the study and “killing the science” by making it seem like pseudoscience. She felt people more knowledgeable about the science should be the ones communicating about these topics.

The study in question only looked at one epigenetic clock and did not present data on other clocks, physical fitness outcomes, or fully characterize the effects.

Levine eventually backed off her criticism, recognizing the personal trainer was just trying to help people understand based on the limited information available, but she maintained her point that more responsible representation is important to maintain scientific rigor and credibility.

BONUS: Kaeberlein Personal Supplement & Medication Stack

Kaeberlein Supplement Stack:

  • If deficient: Vitamin D, B12, and omega-3s
  • Protein powder & Collagen (protein supplement)
  • Pre-biotic – Chia seeds & inulin powder (fiber supplement)
  • Creatine
  • Athletic Greens (basically a multivitamin, in the past)
  • Magnesium
  • Rapamycin

Things to potentially add:

  • Low-dose tadalafil (Cialis)
  • Ca-AKG
  • Urolithin A

Full Transcript (Revised for Clarity and Readability by AI)

Welcome everybody to the longevity Connect for March.. All right. that, you know, just reminding you of kind of, you know, what we do with the clock Foundation, we have active collaborations with with academic research groups and biotech companies and physicians, clinics and DTC companies also. And we, we are really just aiming to enable rigorous use of epigenetic clocks and aging biomarkers in order to accelerate development of reliable treatments for for aging for longevity, and we’re pretty active, so have a lot of different collaborators. And, and a lot of them revolve around these kind of treatment, treatment, testing, and where we’re doing rodent studies, or clinical studies, and just testing a new intervention or a cocktail. And but we also do a lot of basic research on, on the biology of aging. And but yeah, that’s what we that’s what we do, I don’t want disclaimer, we are gonna be talking a fair amount today about an AKG testing group, and about kind of starting treatment, this is a group where people are going to be taking AKG on their own, and with us included, and we’re all going to be taking it and and obtaining biomarker monitoring and then sharing the results and just seeing how that affects these different different measures of biological age. But like with, with any study or treatment, we do encourage you to, to have your own physician and have you know, and and to kind of consult them before making any significant change to your to your diet lifestyle or initiating a new treatment like AKG.

Mark, I’ll just turn it over to you. I think you had some slides, and you wanted to kind of go through some of the basics of the of the trial. But you know, maybe I’ll also just mentioned I think general format for today is that we do have, we do, we are going to be going through some of the mechanics and logistics for the for the AKG group first. And and we’re going to talk about some of the functionality that we have to just make that convenient for people. We’re then going to do this kind of monthly round up where we where we describe some of the recent research in the in the field. And then I think last, we’ll just open it up a little bit at the very end, for some some more q&a. But at any point, feel free to jump in with any questions.

Let me just jump in as well. And I’ll start sort of covering a few things on my side. Yeah, so welcome. I am super excited to have everyone here. So just a little bit of a background. So Bobby is the executive director of the clock foundation. We’re a UCLA nonprofit spin out focused on sort of, like, as you said, the the development of aging biomarkers, epigenetic clocks, and sort of using those towards understanding the effects of interventions, and lifestyle changes. So we’re super excited to sort of kickstart last month, we talked about sort of high level about some of what we were hoping and we were super grateful to all the people that signed up, they want to get started already. So we just figured we wouldn’t wait too long to get started our first group. But we really have a pipeline of ideas, and initiatives we want to do around the sort of longevity idea. So yeah, as Bobby said, he mentioned sort of about us a little bit today, we’re going to walk through a little bit more around what these longevity groups are for, and specifically, the AKG group are our first sort of initiative. One of the big ideas we want to test is there’s been some a few publications and a few sort of discussions or claims, as they say in the longevity space around the epigenetic effects or are taking EKG, we want to as a group, test some of these protocols and other protocols towards understanding whether or not those claims actually work. And, you know, they work in regular human beings like us. So yeah, we’re gonna go through a couple of things today. The the big idea is what we’re trying to facilitate is a different form of participatory research. So we’re really grateful for anyone that’s already signed up and wanted to share this participatory research opportunities for people that want to explore these anti aging effects of different agents, protocols and more. And we have a bunch of Have those on our website that we’re looking to spearhead and run, if you’re interested in bringing something to our attention, or one a leader group, we’re really putting together these over time. And so if you’re looking to do something like that, please reach out and tell us sort of what you want to do, either through the sort of open enrollment, longevity groups, sort of what we’re doing internally as a, as a community here. Or if you want to do something on your own with your own community, we’ve made the bold choice to sort of take our software used for clinical trials used for individuals pursuing and kind of rolling it all together to try to do these ongoing longevity groups. Yeah, maybe Bobby, you could just say two or three, three words on sort of why this kind of initiative is so important does.

You know, I think it’s, we’re interested in more and having more reliable interventional data out about some of these, these treatments, and kind of supplements medications that are available. And so these are agents that people use routinely. And, and, or frequently, there’s a lot of people that are using EKG and metformin and rapamycin, and, and, you know, in there talked about a lot by the field, but there isn’t a whole lot of really reliable data, that’s, that’s available for them. And often, it just takes too long to obtain the these datasets, you know, so, you know, like, starting a trial can can take six months for a year, or, you know, maybe as one example, you know, a lot of people have talked about the tame trial, the tame trial is this large study that’s focused on Metformin, monotherapy. And academics, you know, gerontologist were kind of trying for years to try to fund this really well. You know, but at the end of the day, Metformin is very widely available, and lots of people use it already. I mean, you can obtain it in two weeks, you know, if you want it, you know, from from your own physician, or from kind of different groups that make it available. So it’s a very, and it’s very inexpensive. So it’s very inexpensive, very easy to test. And yet surprisingly, we don’t have great data on how even a simple treatment like that, on its own, really affects epigenetic clocks and other key aging biomarkers. And, you know, and so we’re really just setting up some infrastructure to enable rapid testing and to enable the collection of rigorous biomarker data on treatments that are of interest to us and and others.

Yeah, on our website, we have a few sort of more science oriented kind of write ups on some of the stuff we’re considering in the pipeline. Like Bobby said, metaphor means one that’s, you know, very widely reported easily obtainable, we want to get a little more rigorous data to both individually and collectively to understand these effects. Over time, we have a few others in the in the pipeline that we’re thinking about, we’re actually so excited after this first group that we’re already queuing up some of the other ideas that we want to do, but AKG is what we have up today, we have a small initial cohort to go about this structurally, to kind of talk about it is that is what we’ll be doing is like Bobby said, individually, you’ll be getting your form of AKG. And then you’ll be following, we’ll all be following a shared protocol and add a shared testing points in order to get some sort of shared data that that will then be able to look at and the and the readout, you’ll get, you’ll get your sort of individual readouts or individual reports, and then we’ll anonymize that data and share out a group report on these effects or whatever we observe across the clocks. So I’m gonna go quickly sort of over a little bit of the more logistics of how to participate. So I think one thing to sort of share, broadly is it these are the same tools we use, if you are, say, a clinical researcher, or an academic that you are trying to do this, a lot of these tools are sort of shared across all of our systems and programs. And so you can sort of imagine our longevity tracker really enables individuals on what level to do this, but sort of collective groups to be the to do this. And so we really stand by the science around testing your biological age, we really have two main tests. And just to sort of like, remind everyone, the two main tests we do we provide the phenotypic age female age developed by Morgan Levine and see for that using traditional blood biomarkers. And then we have sort of the latest of the epigenetic clocks looking at those changes the biochemical markers in your DNA that are factor by aging process itself, your lifestyle choices. And as we’re looking to see the sort of interventional studies. And just as another sort of reminder is like this, these features are allow clinicians and groups to be able to launch studies easily recruits patient access, personalized treatment plans, personalized schedules. And of course, we really believe in publishing the results. And so what I’m going to show today is sort of what it looks like primarily from a participant or patient perspective. But if you’re a doctor, physician, or clinician or academic, we can totally repurpose the same software, it’s really built for those things to be able to scale trials and treatments and programs. Yeah, so as I was saying, the the main sort of value props test your biological age, bio, monitor age, biomarkers, and risk factors over time, this is kind of a sample sample schedule, that gives you an idea of what it kind of looks like, you have your latest readout, in this case, scrimmage gives you the option to track your longevity action. So depending on how you want to approach longevity, it’s a huge help both for yourself and for us to tell us sort of what you’re doing. And so if you’ve taken a recent test, we really encourage you to share some of your longevity actions, that kind of keeps you up to date on what you’re doing, but allows us to sort of follow up later to see if there are other opportunities. And the big thing we’re gonna look at today is this this schedule feature. And of course, like we said, we’re talking about participating in longevity groups, and a really voluntary program around helping us understand what really works, and maybe doesn’t work around interventions to sort of reverse the clock, as we like to say. And so yeah, so I’m just gonna go through this real quick and show you a couple of slides, and then jump into the product. So you can see how it works. Your general experience might look a little bit different in terms of what you have in your schedule. But broadly speaking, you’ll have a card showing your biological age scores and your latest reports. We’re really working on integrating those over time. And I think probably even next month, we’ll have some big updates to share with you guys around the new readouts that we’re doing. I mean, inside of your epigenetic readout, there is a lot of data that we’re super excited to kind of share back with you. We use this as a an informational pool, based on the research based on our data science, we then can create more reports and things you can understand Mark, I actually have

a few slides on those. So I at the end, I can kind of go through that.

Perfect. Yeah, and we’ll just we’ll just skip over these for now. But yeah, so you get you everyone sort of after each test, you get an individual report with your your grim age, or whichever tests you’re taking a biological age. One of the things that I just wanted to highlight is that, you know, we also have this this periodic check in, you know, as you change your routine, we’d love to sort of be a part of that journey with you. And so we have our longevity actions check in. And that allows you to sort of say what you’re doing what you’re interested in doing. It allows us to coordinate over time, kind of some of the programs and the groups we’re putting together. And then we you know, what we’ll we’ll be rolling out for anyone who’s already sort of signed up completed all of their steps, you’ll get a very simple treatment plan that allow you to then each week log, what you’re going to do. So I’m just going to run through that real quick. We’ll be getting this out in the next couple of days for everyone that sort of checked the boxes. But let me just go through this on on my side. Let me just put this down a little bit. So yeah, if you’ve joined into one of these, one of these enrollments, you’ll probably see something like this. And if you haven’t completed your enrollment survey, that’s really the first step. So when you go into your [email protected], aging test.com, you’ll you’ll probably if you haven’t completed it, you’ll see your group enrollment survey. That’s really the first high level thing to check off to make sure that you know your qualifier you fit with the kind of stuff we’re doing. Once you once you submit that I’ll send you we’ll be sending you some other sort of emails, most likely, you’ve already kind of completed your first biological age test, and you’ll be able to see that the thing that’s going to be coming out today or tomorrow will be this new survey that that’s basically your readiness to start survey. And so you’ll be getting an email today or tomorrow with that. And it’s a fairly simple idea. Basically, we want to know when did you last complete, you know, in order to be a participant in this program, we really need a big before and after test and so on. The survey basically asked you to sort of tell you when you did your last test. Whether or not we our system as a participant allows you to track not only some of these biological age tests, we’re really excited to integrate wearable data. And we’ve currently integrated with aura soon. So Google Fitbit and a few others. If you’re really keen to integrate your wearable data, and you don’t see it in our current list, we can do our best to try to get you set up relatively quickly, we have a pretty good infrastructure to do that now. So if you’re keen on that, and you’ve already got a subscription, or you’re ready to start your subscription, just just send us a note. And we can make sure we can try to get your wearable data included. So yeah, this is a fairly quick survey, just to make sure that you’re ready to participate, there’s really two main questions that we want to sort of say, well, whether you’ve done your, you know, your first biological age test. And then as we said, this is sort of a voluntary process, which form of AKG you plan to take, we currently have two or three that we recommending, the study that we’re really basing our program on our group on is rejuven. And that’s, as we see is a little bit more expensive. Some of some of the people are planning to take this and some of us plan to take a slightly more affordable option. These are the three we have, they’re all available in both sort of supplement kind of distributors, Amazon links. And so we just asked you to tell us which version you plan to take. And then just take a look at your bottle just to see in the back what the recommended what you plan to take daily. And so you’ll enter that in here. And when you plan to start, let’s assume I’m going to start on Monday, and then agree to the terms and conditions just so that we all agree that we’re going to do our best to follow the protocol and sort of report through surveys, any side effects, any issues you’ll sort of have. And so once you submit that, we’ll be notified on our end. And then I’ve already set this up for myself, but you’ll be then getting in a few days or a few hours even will be setting up your individual setup, which will include a treatment plan. In this case, I’ll be taking the pro health EKG. And then once this is all set up each week, our big ask is just to go in once a week, ideally, not require you could come back after a few weeks to do it. And just log your your your weekly survey. So you’ll see in here and if anyone wants a daily tracker, we can set that up as well. But we’ve set this up as a weekly tracker. And so what you’ll end up wanting to do is then show you on this one. Yeah, so you’ll then get a weekly survey, and sort of this is from the more full setup version. So you’ll get in your your treatment plan, the ability to that log, your weekly survey, and I’m gonna skip over this for now. But basically, it will just be a confirmation that you’re following the protocol, any lifestyle changes, any side effects, and sort of if you want to share some additional add home measurements. But yeah, that’s the sort of the quick spiel on that. Just to sort of review the way it sort of will work as you’ll, you’ll be receiving in the next day or two a an email from us talking to sort of are you ready to start, if you haven’t quite finished some of these other stuff, we’ll send out a couple of more targeted emails to sort of make sure you get your plan set up. But once you complete that readiness survey will then sort of set up your treatment plan. If you have a playing card and a simple sort of weekly survey, and then you’ll also be getting in your schedule, your additional bio age checkpoints. Yeah, I think those were the main things. And then one last thing to sort of share as sort of the what’s the what’s the reward for participating. everyone that participates will get their own what we call our longitudinal tracking report. This is really built around understanding at least two testing points. I think this is actually an example from Steve. But yeah, basically, this will allow us individually to track changes over time. And because we’re doing an intervention, we’ll see those differences. And then additionally, we’ll be able to look at different clock changes. So not only do you get to see your readout from current age, we look at several other clocks to see how your aging might have been affected. And additionally, we’ll then be building out a group report to see changes over time. But yeah, those are the big ideas to sort of how to get logistically set up and what it involves. Maybe we can check to see if there any questions or additional things you wanted to add there, Bobby?

Yeah, I see. There’s one question just about the structure of my aging tests.com and clock Foundation. And just to clarify that, though my aging test is owned and managed by clock Foundation, and and clock Foundation is a 501, C three, nonprofit. So so it’s kind of, again, it’s it’s owned entirely by cloud. And we collaborate with a lot of startup pharma companies and academic researchers, but but we’re very much in an independent group, and kind of designed that way to where, like our mission is to is to provide rigorous testing for groups and kind of unbiased testing for them.

Yeah, so I would just, I would say that the clock foundation.org is sort of where we set our route everyone for we have a great a great page, if you have sort of questions about all this, it’s a it’s at block foundation. What is it getting get started. So I would recommend if you’re sort of interested to sort of know about our services, and our different offerings and different stuff, check out cloth foundation.org/get started, and in there, you’ll sort of see how all of our different umbrella of services and platforms all integrate together. The clock foundation.org is really for the nonprofits making sure that we understand where we fit. And then we have some other different portals that sort of our use specific, my aging tasks really fits under the sort of our software offerings, our portal offerings, how we manage individuals taking tests, and then how groups all fit together. But that’s really where I would sort of recommend if you have sort of additional questions, or you want to look at that,

yeah, we just had another question about about whether or not we supply AKG and we do we do not so so you would have to obtain the AKG on your own. So in the in the intake survey, and maybe on some some other pages that kind of describe the group, we do provide a link to different forms of it that are available. And I mean, these are mostly Amazon links. So like for, for people in the in the US. There are also some some UK brands that are available. But we I mean, there are several that are available, I think that are largely, I mean, they’re pretty similar. So you can you can you can find out about those kind of on that that site, or, like once you join the group there, again, there’s gonna be a survey, which will provide direct links to it. And I think, yeah, I mean, it kind of depends on what the dosing is for it. But but you know, it might be kind of 40 to $80 per month, you know, for the for the AKG.

Just so it’s like we’re all on the same page, just so we have at the my aging test.com site, we have a kind of a detailed write up of sort of the details. But yeah, so you’ll be taking the you’re up buying the EKG on your own, we kind of SPECT it at about 30 to $50 on the low end. And then there’s a few other providers that are more about $100 a month. And then I mean, the the overall way it works is you’ll you’ll acquire your own EKG. And then we have sort of two main test points you’ll be doing over six months in order to get kind of this before and after. And as you take each test, you’ll get your your standard group age reports and standard monthly wearable kind of aging biomarker reports, and then this special final group report, which will will be at the end of it to kind of understand collectively, what were the effects of this? Right.

Mark, I’ll just share my screen now. But I just wanted to mention these these additional reports that are that are available, or it’s kind of more what just this like what you obtain from a monthly subscription or an individual test. And so this is the grim age report, which you may be familiar with already. But it looks at your grooming age score the individual components, and then it breaks it down by your leading risk factor. And there’s additional recommendations for different interventions or treatments that may potentially help it. We also have this new version of the grim age report that’s now available by default. And it’s called the systems aging report. So it kind of links the different grim age components to specific tissue Use our physical, physiological systems, and it presents it that way. So you could say that your your cellular brain aging, now, may may be kind of the leading risk factor. And but yet, it’s now presented in that way for you. And we also have for everybody that joined that has a subscription, they’ll obtain not only grim age, but phenol age testing. And so this is a marker that’s just based on several routine clinical tests. And we can obtain the results pretty rapidly. So once you in the US, most of that testing is done through quest today. So you’d go into a quest on your own, obtain a blood draw, they draw several tubes from you, and you’d, and you obtain a fino age report within about a week. And that will give you a quick read on on this measure. It’s a pretty widely accepted measure of biological age. It’s not an epigenetic test, it’s a little different, but it is a it is a nice kind of real time biomarker to use.

And here’s a longitudinal tracking report. Mark talked about that.

This was one quick question on what array we use, whether it was the 450 K, the epic array, or? Oh, yeah, I

think David was kind of referring to I see that. And yeah, I mean, that’s probably what happened, you know, he was referring to kind of a separate project where he submitted some prior results for analysis. And if it is, on an older version, like the 450 K, you know, you might, you might have, there might be some some more kind of noise or variance in the results, because you have to impute the missing methylation sites. But yeah, we can, we can kind of take that conversation offline. But here’s the the, so everybody that joins the group, and obtains a subscription also is able to obtain wearable tracking reports. And the most robust and report we have available now is based on aura ring data. So if you have an aura, and you registered it, you’ll obtain this PDF report, a digital health biological age report that looks at your sleep, it looks at HRV. And it looks at several other it looks at activity and several other measures. And and it you know, and it provides kind of a snapshot of like aging related biomarkers that are available on the aura ring. Beyond that, we provide these this kind of raw biomarker data from several different wearable devices, including Fitbit, Google, and there’s a few others that we add, and we provide, again, that’s in a similar format to the the longitudinal tracking report, because this is wearable data, you’re collecting it every single day typically. And and so we just provide kind of the raw output for you to track and to see how that and so you can pretty readily see how any of those those markers change over time or in response to treatment.

And here’s a report that it’s an expanded epigenetic biomarker report, and we’re calling it a summary report. So our initial ones focus largely on grim age and its components, which we and also kind of ways to modify it, which at which I think is important, and that we want to make are all of our reports that have actionable and kind of meaningful for, for you for us. And, but you know, there are a lot of additional biomarkers, some less reliable than others that can be made available, like just through the same test that they’re already available through the same tests you’re obtaining when you obtain a grim age test. So we’re now making these longer epigenetic summary reports available. And and so that’ll have information on for instance, predicted telomere length, there’ll be predictors of complex health traits, like BMI or smoking status. There’s also many different predictors of immune system aging, biomarkers, and, and methylation risk scores for different kind of multi omics data for proteins and metabolomics data. So in these are going to be available in a PDF report initially, for a lot of people you’ll you’ll obtain it just like an a dropbox folder, where you You’ll have access to it. And, and you, in some of the people that have also requested raw data, they’ll also obtain their raw data in a shared dropbox folder. So that’s where initially, you’ll kind of see these reports. And then, you know, as Mark mentioned, like, within a month, couple of months, we’ll also be making them available and on the web portal.

And I see there is this question about the biological age test, and the subscription in order to participate. That’s right. So so it is a requirement to obtain a subscription in order to participate in the group. So I mean, it’s kind of a, you know, in the end, that’s kind of the deal, you know, we’re all going to be buying our own AKG, we’re all going to be buying our own testing subscription. And then we’re going to do that for six months or more. And then we’re all going to be able to kind of share data and have a group analysis report. So yeah, that’s, that’s a critical, that’s a critical part of it. So you have to obtain a subscription, a bio monitoring subscription. And so there are two versions of that we make available one is $50 per month. That’s like kind of the basic plan that has the wearables data with fino age testing. And then we also have a kind of one that includes epigenetic clock testing. So that’s $150 a month. So but yeah, so that would be the monthly cost. And then you have to add on top of that, the the cost of the supplements, in this case, EKG, which I think Mark mentioned 30, to $50, yeah, maybe 40 to 80, depending on on your dose, it’s something in that range. So yeah, there are some costs you have to bear and one of them, you definitely do need a subscription plan in order to be part of the group.

All right. And again, we will kind of open it up at the end for more questions. So and maybe, you know, we don’t we don’t have a very long, kind of monthly recap here. But we’ll probably I’ll try and spend about 20 minutes on that. And again, feel free to jump in if you have questions at any point, but we’ll open it up again, at the end. And, and these, these monthly recaps are really just I mean, there’s, there’s a lot of information, a lot of different sources of information out there. There’s the scientific literature, if you if you’re the type that read scientific papers and kind of digs into at that level of detail. You know, there are also lots of kind of influencers, people on social media, people with podcasts, that that are talking about papers. And and, and but you know, we really just try to, and I think this is this is the gist of it, again, is that there’s there’s kind of a ridiculous amount of information about about aging research and about new treatments that’s becoming available every month. I mean, there’s just been this influx of interest and work in the field. And we just want to capture the most relevant information. And be sure that we’re we’re always working with it with the best available intervention, and the best available information.

And here is just epigenetic clock technology. So there are a few papers that came out. And I guess the first one here on this middle paper is just an example of just just to kind of kind of highlight the the power of epigenetic clocks are generally I mean, I think probably everybody here is, is is pretty well aware of what epigenetic clock clocks are, but it’s just a biomarker that can predict somebody’s age, to within about a year or two, now in a very unbiased way. And this group came up with a new age predictor, a new model that’s based only on 11 sites in the in the methylome. And in this add an area under the curve, so this is like a measure of how accurate a predictor is, of kind of point nine, seven so you can think of like No, almost always correct for distinguishing young versus old samples. So a very simple measure, something like that could be available very inexpensively for for kind of, you know, and it’s, it’s pretty good for for kind of distinguishing young versus old samples. And, but, but then there are also other technologies that are that are coming available. So like, here’s a paper that looked at cell free DNA. So that’s just using. Normally for an epigenetic clock, we’re using DNA from cells from the nucleus, typically bulk cells. So it’s it’s a, it’s a group of cells, where we’re analyzing how that changes over time, and producing an epigenetic clock readout. So this looked at kind of DNA from the from the plasma, so outside of cells, and they were, and they use a somewhat different measure, but they’re also able to kind of predict age fairly well with it with it to within a few years. And And finally, there’s a third paper here, that is, is no, I included, just because I think it’s kind of representative of what you’re going to be seeing in the in the next two or three years, is there’s there’s a lot of people in the field that are now working with single cell methylation data, like I mentioned, the clock readouts that you’re obtaining with grim age that we’re obtaining are from a bulk sample, they’re from a blood sample, that’s a mixture of different immune cells and blood cells. But But, and a lot of people now are looking at single cell data, and they’re understanding how each cell in that group is changing over time, and how that’s contributing to to aging. And this is, you know, it looks like one of the, I mean, there’s, there are a lot of, there’s a lot of work that’s already been done on the field, but it’s becoming a lot more sophisticated. And you’re going to be seeing a lot more papers like this emerge. And it really that where people are starting to understand kind of what are the mechanisms behind the clocks, and what kind of drives epigenetic aging. And, and this type of single cell technology is going to be very important for that. This is just a general science topic. And it was something that, that they found this new kind of, quote, life form, it’s a virus, like, they call it an obelisk, that that is it infecting your microbiome, that they never knew existed, and it’s now they’re able to find it, I guess there’s better sequencing technology, they’re able to discover it. But this is something that we never knew about. And, and it’s worldwide, and it’s in there in 10% of the population. So it’s, it’s very, very prevalent. And to me, it’s just a just kind of a sign that there is still a lot in the field we’re learning. And that, you know, and for instance, like a big role of methylation is to kind of suppress some, like, kind of ancient DNA, that a lot of that’s derived from viruses that are infected our genome. And, you know, and so, I mean, there’s a lot, we’re still learning kind of about that. But at the same time, there’s also kind of treatments that are available that work to address these things like, like drugs, that that kind of suppress those viruses. And those have already been shown in some cases to improve epigenetic aging. And so there are, you know, kind of even based on, I mean, there’s still a lot we’re learning, but there are also kind of tools we have available, different medications that can already kind of be used in.

And here are several papers that came out just looking at epigenetic. These are kind of clock data, clock results papers. So one paper that came out, kind of right after our last meeting, was this one of validation of biomarkers of aging. And, you know, and kind of often I think researchers get together and they published papers about about biomarkers of aging and it seems like about every decade or so, there’s a big a big meeting and people kind of talk about biomarkers and you know, which which are the best and you know, which should be applied. And, you know, and in this paper, you know, they they talk about kind of These different forms of validation. Oh, you know, that’s, that’s a word that gets bandied about a lot, I think in the field is whether or not a biomarker is, is validated or not. And you can I think you can probably already tell that, you know, there’s five different forms of validation. It’s something that, you know, people, you know, I mean, a biomarker can be kind of validated in one way, but fatally flawed in three others, you know, so you have to really be careful about which which biomarkers you use, you know, I mean, often they do have very big kind of gaps. You know, and I think, kind of one and I will talk about that kind of inherit. But, you know, here’s, here’s another paper that looked at, at epigenetic clocks, and just their links to future onset of different age related diseases and kind of future prediction of healthspan and lifespan, and found that grim age outperformed other epigenetic clocks. And, um, it’s not, you know, it’s it’s kind of a leader for the field for a reason, it often works in these independent datasets. And in large, diverse populations. And this is just another example of of it performing very well. And they’re also here, here’s a couple of studies that look at Mendelian randomization studies. And these, these are also pretty complex studies, I don’t know if you’re familiar with with Mendelian randomization, but you basically, are kind of looking, you’re trying to stratify a population based on their genetic risk for epigenetic aging, and then helping tease out from differences in those groups. If if epigenetic aging is kind of causal, if it’s causing increased mortality, or in the, in these cases of these studies, is epigenetic aging, causing aortic valve stenosis, this something that’s very, it’s associated with two year mortality and more than 50%, so it causes a lot of morbidity and mortality. And there was also a study that looked at does epigenetic aging, cause obesity? Or is it the other way around? And, you know, in both of these studies, they found that there were there were signs that that epigenetic clocks weren’t causal. You know, they were kind of drivers of these pathologies. But you know, with obesity, especially at work both ways, obesity drives epigenetic aging, and, you know, but but, you know, I think these studies in general, and also these papers, papers like this, you know, they’re often written because there’s not that much reliable, interventional data. So there’s not kind of, I mean, people have to, it would be a much more straightforward study, if you’re trying to determine, you know, if, if, if epigenetic aging causes morbidity or mortality, if you just have a treatment, it could be AKG. It could be anything else that reverses epigenetic aging by three years, or five years or eight years. And then you just wait and you see, does that lead to reduced onset of cancer, cardiovascular disease and dementia? That’s the study everybody wants to do. But kind of the problem is there isn’t that type of interventional data available, you know, people haven’t kind of shown that any treatment can very reliably reverse these key biomarkers of aging. And this kind of and so people are doing, you know, these these studies and very roundabout ways, you know, and kind of talking a lot about it, but really what the field needs is interventional data and exactly the type of data that like with our AKG testing group and our other groups that we’re aiming to obtain.

One second

All right.

All right, I’m back. So the end, I’ll jump now to some other aging biomarker news, maybe more straightforward kind of news, but people looked at at proteomics. So and they’re wondering, can proteomics predict onset of dementia and Alzheimer’s, and this has been an area where methylation and epigenetic clocks perform, okay, but now they’re not super accurate predictors of Alzheimer’s or dementia risk. And so I found this to be an interesting study, and this group, and they did find that a couple of markers, a couple of proteins, in particular, were very strong predictors of future onset of dementia, or Alzheimer’s, and one of them was actually gdF 15, where that is a grim age component. So we we in every methylation test, we have a surrogate predictor of Gd, F 15 levels. And, you know, I think we can likely also predict levels of GFAP and some of these other measures. So I think in future months, we may be able to roll out some amount of of these measures, now just include them, like as another additional kind of outcome in our reports, and I’ll be working and, you know, I’ll be working with academic groups to help kind of ensure that that those measures are meaningful. And here are a couple actually a couple of studies that, you know, it kind of, I guess the question, especially with Alzheimer’s or dementia risk is, like, is there anything you can do about it? And there were a couple of studies that came out showing improved cognition, and, and you know, and these are kind of what, you know, I would say, I mean, these are typically the other randomized controlled trials, to large academic centers that perform them. You know, I think this one on the bottom was a cocoa and multivitamin study, and, in this study looked at exercise together with a prebiotic or a probiotic, and they found some kind of modest effect on on cognition, and kind of the same with this with a cosmos study. I think there’s a lot more analysis on Cosmos that’s still underway, including looking at epigenetic clocks, but but they did find a modest and a benefit to cognition from this, this regimen and but now, I’ll just move on to some of the an influencer and different initiative updates. And, you know, maybe the more sensational info that’s out there. And, and, and their overall. I mean, there, there weren’t kind of that many major updates from these different aging research initiatives, at least that I saw. And but, you know, one initiative I just want to highlight is this. I think this is longevity biotech fellowship. And and Nathan Chang leads that that group, and it looks like they work to put together an lbf a roadmap for for kind of aging research are really I mean, they highlight indefinite lifespan. So it’s a group that’s very serious about on a radical life extension. So they’re not kind of taking a you know, a traditional pharma or biotech approach. They kind of highlight these couple of different areas like tissue and organ replacement, or cryopreservation that they’re looking to hire Light. So I found that kind of interesting that they they produce this, this nice kind of roadmap, you know, it’s kind of intended to be a technical roadmap for for people kind of that are that are interested in kind of radical radical life extension.

So, so I mean this, this slide just talks about LA, if, you know, I don’t know, how many of you follow

I was just looking at a question that we had come up

and I think the question was about, is it possible to conduct your own experiment on rejuvenation? Based on your your watch? Stock? You know, and maybe that’s based on wearables? It maybe that’s what the question is about, feel free to jump in, if I’m not getting that, right. But But yeah, absolutely. I mean, that’s what if you, if you obtain a subscription, you will obtain fino age data, and wearables data. That’s, that’s our basic subscription. And, and, you know, with with any of those plans, we just make it very easy for you to track these biomarkers over time, and to log whatever interventions you’re taking. And so you can very quickly determine whether or not a treatment is is working for you, or if it’s influencing any of those biomarkers. And with the wearables data, especially, there are multiple time points, you know, it’s not like you’re getting, you’re getting three time points in three days often. And so we also layer on statistical analysis with every wearables tracking report. So you can you can get like a rigorous kind of understanding of whether or not those biomarkers are being changed very quickly. But yeah, let me just get into some of this drama. I don’t want to spend too much time on this, but it is drama in the longevity field. And many of you may have seen this, but but I think it all started when David Sinclair came out, and I’m talking about some new supplement that that, that he had written it, apparently, it reversed kind of reverse aging and dogs. And then Matt Caber line, and all well known aging researcher, just just, you know, kind of said, that’s a lie, that it’s proven to reverse aging and dogs, you know, and as you know, he’s kind of saying that the the data, which is shown here, is very a flimsy or weak. And that is kind of claiming that in no way shape or form. Is that really, should should, or could that be equated with reverse kind of reversing aging. And David Sinclair pretty quickly kind of changed to, you know, is messaging on it, to kind of say that it only slows the effects of aging. So it kind of backed off. But then also, you know, there was no, they kind of Matt Caber line resigned from this group, they were both part of that he was that he was leading. And then David Sinclair also resigned from the group. So there was a little exodus from this, this aging, this group of aging researchers, and, you know, but you know, I think it’s seems like anyway, you know, I think it’s healthy for the field that people are really arguing about the messaging and trying to hold people accountable for having kind of responsible and of messaging about about these biomarkers. There was kind of a similar discussion, and this was just maybe last few days or last week, where where I Morgan Levine, Dr. Morgan Levine, she reacted very strongly were were a group trying to highlight these findings where there was a treatment that apparently reversed aging by by five years and eight weeks and you know, so I mean, there was this this kind of post by a personal trainer that kind of read this study and and saw that it reversed biological age by by a parent apparently reversed it by five years and only eight weeks and so she reacted very strongly saying these influencers are kind of killing the science and that you know, it’s it’s making it all look like pseudoscience and that you need kind of people that are that understand it better to be the ones that are that are talking about it. You know, I you know, I think she eventually kind of backed off and realize this is just a personal trainer. Like trying to help people understanding it, you know, the best that he can, you know, he’s got a big following Lucky’s largely doing kind of good work. And so, but you know, I think she does have a very much have a point, though, you know, especially with a study like this. So and maybe, you know, one of the big gripes is that you’re saying it’s, I mean, I guess they put the word potential in the title, you know, so it’s not like a firm, firm finding. But, you know, I think what a lot of people argue about is what is defined as biological age. And in this paper, they, they only present data on one clock, and they don’t present any other data, they don’t present any functional outcomes. So they don’t look at physical fitness, or vo two max or, or any of the other use a single clock. And beyond that, I mean, they they use a platform where multiple clocks have been calculated. So, you know, they have the data, but, you know, what is it, you know, maybe one clock shows five year reversal, but the other clock show nothing, you know, or two years, you know, it’s so it is a little, you know, and if people don’t show the data, you know, you know, it’s often not not a great sign, you know, and maybe, you know, and, you know, in and so, I mean, I think that’s probably what’s kind of driving some of this frustration, but I think it is a very valid kind of gripe and kind of concern, you know, that, you know, if if people are kind of presenting, and I think, you know, this is all to happen all too often in science, where people kind of present the best version of the findings, and they kind of withhold, you know, some of the key, you know, some other important results. And then, so, work like, that is another reason why, you know, we want to do our own groups, and to have access to the data and make it make it available to kind of the good, you know, the good, you know, with the good with the bad, right, we want to see kind of all the data and understand what effects these treatments have or do not have.

And I found this one interesting where Matt Caber, lining this guy who was pushing back on David Sinclair, you know, very, very hard, he released his own personal supplement stack. And so you know, and you can find out kind of, you know, what, you know, if he’s an expert in the field, like, what is he doing for himself, and he kind of listed those things. So and I think that’s something that we want to also pursue, is that, if you have David Sinclair over here, saying that nr and resveratrol are kind of the, you know, and he does a few other things beyond that, you know, are the way to go and you have Matt Caber line, saying, This is what he’s doing it, these are very easy things to compare. They’re very easy things to test. And so we can we can launch groups that that do that, you know, so that’s something we’re interested in doing over the next few months.

Think I’m going to wrap it up there?

So one quick question, Bobby. Sure. I guess I’m curious, when we have someone doing five things like like five supplements, how easy would it be to sort of decoupled to understand which would be the big drivers say we would all want to do a five substance intervention or 10 things? How easy would it be able to see which might be the biggest contributor? Or is there any approach when you have so many multiple factors going on? Or is that better to do with substance

by substance?

I feel like it’s better to do a shotgun approach when there’s a when there’s a reason behind it, you know, and kind of the problem is that when you have a mono that I mean, going back to like the team trial, so the team trial was a study that was trying to get funded by the by the field that was going to cost 60 million or $80 million, or something to study Metformin, monotherapy. So Metformin as a standalone agent, and so often, though, people just just you know, people aren’t taking a single agent, and then often when you do use it, the effects just aren’t very strong. So you can end up doing these really large studies, very good science, randomized control trial, and then you end up having almost zero effect. Right? So I mean, I would rather be a little biased towards a shotgun approach, a drug cocktail, a treatment that we that we believe in will have a kind of profound effect on aging. And then when we figure out these five compounds, reverse aging, very considered reverse epigenetic aging or these other measures by five years or eight years, very consistently, then we deconstruct that, then we separated it out into different groups that try these three versus those three, right?

Were there any questions from anybody who’s still hanging out with us where we jump off?

We’ll call just to summarize, for anyone who’s sort of still hanging around. If you’re already in the longevity group, you’ll be getting a couple of emails from us to sort of finalize your treatment plan and some of the steps if you haven’t yet, we would love to have us either submit to our sort of enrollment survey or one of our other programs. We have a, you know, an ambitious plan over the next months and years to try to look at different interventions in order to get data for some of these key questions around what you can do to live longer, healthier, etc.

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