Matt Kaeberlein - The Dog Ageing Project | Part 1 | Let's Talk Pet Longevity

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Let’s Talk Pet Longevity is a talk series, hosted by Avi Roy & Laura Minquini, focussing on exploring the reversal of aging, and enhancing health and life span of our favourite non-human buddies.

In what is the first episode of Let’s Talk Pet Longevity, we are delighted to host Prof. Matt Kaeberlein. Matt is a Professor of Laboratory Medicine and Pathology at the University of Washington School of Medicine. His research focuses on the basic mechanisms of aging in order to facilitate translational interventions that promote healthspan and improve quality of life.

Matt is also a co-director of the Dog Aging Project, in Washington. By enrolling over 32,000 dogs, the goal of the Dog Aging Project is to understand how genes, lifestyle, and environment influence ageing.

The hosts:

Laura Minquini – the founder of MYKIGAI, a DTC longevity platform dedicated to the education, vetted curation and management tools for people to get on board with longevity as a lifestyle. Having spent most of her career in trend forecasting and branding design and fashion products she sees the potential of longevity becoming the next big consumer category empowering people to take their health in their own hands.
Avi Roy – a biomedical scientist and entrepreneur based in Oxford. He advises and funds startups in the health and longevity space in North America, the EU, and India. He also work with governments to develop and refine policies that enable the longevity infrastructure.

The questions:
(The timestamps relates to when the question in asked in the full video)

03:51 – Intro

05:23 – How do you define ageing? And do you think the variability in answer to this question from different researchers in the field is indicative of a problem?

09:09 – Can you tell us a little bit more about the Dog Aging Project, how it was started and where it is now? And a little bit of an overview and coming to where we are today?

12:57 – Why are dogs such an interesting model to study longevity?

16:33 – Can you tell us a bit more about the process of biological ageing of dogs?

21:06 – How are you measuring biological ageing in the dogs involved in the project?

25:28 – What do you think is equally or more important than the functional measure of the epigenetic clock

28:52 – Can we extrapolate the results of the dog ageing project towards human longevity and human aging?

34:27 – Where are you at with the dog ageing project at the moment? Can people still enroll their dogs in the trial?

41:40 – What is your longevity protocol for your dogs?

*Matt with his two dogs: Dobby (German Shepard) and Chloe (Keeshond). Photo credit: Tammi Kaeberlein*

Here’s what was said:

Laura Minquini: Matt, I’m going to let you give a quick intro to yourself before we proceed to some questions. And thank you again for being here with us today.

Matt Kaeberlein: Sure. So thank you, Laura and Avi for the invitation. This is actually my first clubhouse event. So, also thank you for pulling me into the 21st century here. So it’s really great to be here. I’ve been interested in the biology of aging actually since I was a graduate student. I did my graduate work with Lenny Guarente at MIT. At that time working in single cell budding yeast. And as my career has progressed, I’ve gotten more and more interested in which aspects of biological aging are evolutionarily conserved. And then, how can we actually use this information to have an impact on health and longevity in the real world? And certainly I have a strong interest in translation of this science to improve healthy aging in people, but it occurred to me seven or eight years ago that companion animals and pet dogs in particular are a really fantastic opportunity to actually bring aging research out of the laboratory and into the real world. Hopefully in order to help our pet live longer, live healthier and thereby enhance the quality of life. Not only for our pets, but for the humans who love these dogs as well. So the goal of the Dog Aging Project is to understand the biology of aging in pet dogs, and to use that information to maximize healthy longevity in pet dogs.

Avi Roy: Thank you Matt. That was actually going to be my first question. Your answer, which was that can you tell us a little bit about your background and how you got interested in this, but you’ll already covered it. So I’m going to move on quickly to the second question. By the way, everyone on this call, we have a few questions, Laura and I have a few questions. We had actually had a lot of questions, but we are limited to a few questions. And then we’ll open the floor up for any questions that you guys have in about 30 minutes or so. And so the second question is actually written by my graduate student, so it’s written in first person, so it sounds like I’m actually asking it, but this is the student that is actually asking it. But it concurs my feelings as well. So one of the things that Laura and I and my research students do, is ask researchers ‘how do you define aging?’ And this may be a tricky question to ask, but the variability of answers is quite big from different researchers who are working in this field. So firstly, how do you define aging? And secondly, do you believe that the fact that there is such variability in the answer of this question, that is indicative of maybe a problem or at least some kind of concerns in this field of longevity?

Matt Kaeberlein: So first of all, let me just say that is a fantastic and really important question. So kudos to your student. And I agree completely. I think when you ask that question, you will get a different answer from almost anybody in the field. And honestly, I think a lot of the disagreements that I see happen between colleagues and even disagreements that I’ve gotten in with other people in the field can often, when you finally get to the core of it, come down to we’re starting with different definitions of aging and what we mean by that. So I think this is a really important question. So first of all, let me say that I actually, I think like most people, have multiple definitions of aging and it really depends on the context. So, I think I naturally given that I’ve been working on the biology of aging, for more than 20 years now, when I think about aging, my initial sort of process is I immediately gravitate towards biological aging. So that’s really the first sort of decision point in this definition, right? Aging can mean the passage of chronological time. It can mean geriatrics. Changes that occur in the elderly. I naturally gravitate towards mechanisms of biological aging. And that’s usually what I mean when I use the word aging. And then, within that realm of biological aging, I think again, you can have multiple definitions and I naturally gravitate towards functional and molecular definitions of aging. And one way to think about that, and this is imperfect, but I think it’s the best we have right now are the hallmarks or pillars of aging. These highly shared molecular processes and pathways that seem to affect the biological aging process. That’s what I mean when I talk about aging. And then over the last few years, I have very much come to believe that the manifestation of those molecular processes in terms of functional declines, that go along with aging, are what are really important when we’re thinking about translational approaches or translational geroscience. What we really want to do is improve those functional changes, that impact quality of life. And so that can be, disease-based, like dementia or diabetes or heart disease, but it can also be more subtle things like arthritis or chronic pain in your joints or… like I had a something called frozen shoulder, which is inflammation of the shoulder capsule. That’s not a disease we usually think of with aging, but it really affected my quality of life until I got it taken care of. So I think those are the kinds of things that I started to value more when I think about aging. How do these hallmarks or pillars of aging impact quality of life and functional outcomes as we get older.

Avi Roy: Thank you, Matt. Your functional and molecular obviously, as syncope with anybody who is like myself a molecular biologist or a cell biologist. So I completely appreciate that. Can you tell us a little bit more about the Dog Aging Project, how it was started and where it is now? And a little bit of an overview and coming to where we are today?

Matt Kaeberlein: Sure. So I’ll start with the history. And actually the Dog Aging Project proceeded me. So it was really the brainchild of Daniel Promislow’s at the University of Washington with me and Kate Creevy, who’s our chief veterinary officer and she’s at Texas A&M University.

[00:09:46] And actually, they were both at the University of Georgia at the time. And basically got interested in the idea that dogs could be a very powerful genetic model and environmental model to understand what are the factors that influence aging. And so they started a network. It was an NIH mechanism called an R24, which is a network grant to bring together people to think about a topic and come up with next steps. And so they have the canine longevity consortium. And that’s where I got involved and had sort of initial discussions with Daniel and Kate and several others. And then when we recruited Daniel to come to the University of Washington, that’s when really started to put the foundation in place for what is now the Dog Aging Project. So Daniel and Katie were really, I think, interested in genetic and environmental correlates of aging. For me, what really got me excited about the Dog Aging Project was when I made the connection in my head that not only are dogs very powerful for understanding correlates with healthy aging, but there’s actually a real opportunity to slow aging or even partially reverse aging in our pets. And I’ve always been a dog person. I’ve had dogs all my life. And I think like many people, I love my dogs and have considered them a part of my family. And it was just this moment that clicked for me that, if we could actually have an impact on the healthy longevity of family members. And I think the statistics are that more than half of pet owners consider their pet part of their family, that can have a huge impact on the field and on the quality of life for people. And so that’s what really got me excited. And we can talk more about why dogs are a particularly powerful system in which to test interventions for aging. But that’s what really got me excited about it. And so then Daniel, Kate and I really got together and decided if we’re going to go for it, we need to go for it. And we started outlining what the Dog Aging Project was going to be. Trying to seek funding. It took really probably four or five years to get the first big NIH grant to build the Dog Aging Project. And that happened, I guess, about two and a half years ago now. And so now what we’ve got is a platform that really has two major goals. One is a longitudinal study of aging, which is just observational and the goals are really going to help understand what are the most important genetic and environmental components of healthy aging in pet dogs. And then we also have an intervention component which our first clinical trial is called the triad for test of rapamycin and aging dogs. And so I think these are mutually beneficial goals. One is to understand aging. That’s the longitudinal study. The other is to do something about it. And that’s the clinical trials. And that’s where I see us going into the future. We’ve created the platform now. And I think, now we can continue to move on in the future. We’re going to get a ton of really cool data over the next couple of years. But hopefully we won’t stop with rapamycin and hopefully we’ll be able, or other people, will be able to use this infrastructure to test other interventions to get to the point where we can actually have an impact on healthy aging in pet dogs.

Laura Minquini: Thanks for that, Matt. I had my set of questions, but I think if Avi agrees, that maybe it’s important that you go straight into saying why the dog is such a good model to prove some of it to study and then to prove some of these trials on, before moving to humans. Can you explain this? I think for some people it is obvious, but it is important to people now.

Matt Kaeberlein: Sure. So, there are actually lots of reasons, but I think some of the big ones are, first of all, from a public recognition of the field perspective. I think that this has a huge potential. I think all of us in the field recognize that among the general public most people don’t have an understanding of where the biology of aging is today. I think honestly, most of the general public still thinks of it as science fiction or snake oil. And there are a lot of reasons for that, but I think that’s just a fact and I think that if we’re successful at understanding aging and ultimately, having a clinically demonstrated intervention that increases lifespan and health span in pet dogs. I think that’ll really be a watershed moment for the field and it will really shift the way that the general public views aging biology. I think it’s going to be much easier for people to understand that aging is actually malleable, once we can do it in their pets. So I think that’s the biological region reason for why dogs are a great model and opportunity. But I think it’s a really important one for the future of the field. I think when you look at the biology, there are also some obvious things that are important. One is, dogs age faster than people do. We’re all familiar with this idea that one human year is about seven dog years. And that’s not perfect. If you’re interested, we can talk a little bit more about that. But it’s pretty close. It’s close enough. And that just means that dogs age about seven times faster than people do. So the importance of that, is that you can actually do experiments in a reasonable amount of time. A longitudinal study, that would take three decades in people and will take three or four years in dogs. And that’s much more amenable to both the pace of scientific research and the sort of typical grant timelines. Most NIH grants are five year grants. So you can actually accomplish stuff in a reasonable amount of time. For our clinical trial of rapamycin, it’s a three year clinical trial where we are statistically powered to detect lifespan as the primary endpoint. You just can’t do a lifespan study in healthy, older people. It’s just not feasible. So that’s really important. I think the other big one is that dogs share our environment. 99.9% of the preclinical studies in model organisms in this field have been done in the laboratory. And in the laboratory, we intentionally try to control the environment as much as possible to reduce the noise and enhance our opportunities to see significant outcomes. But the consequences are that you lose all of the environmental variability that humans experience, on a constant basis. Pet dogs share a human environment in pretty much every way. The one area where it’s not quite a great match is diet. But other than that, they really experienced all of the same environmental factors that we experienced. And that almost certainly have a huge impact on the aging process. I think the current estimates are that about 75% of longevity determination in people is environmental or at least non-genetic. So, I think we all recognize that environment is really important, but we don’t have a good way to study it in the laboratory. And pet dogs give us the opportunity to do.

Laura Minquini: I am very glad that you mentioned how it’s the one first thing why showing that longevity science, or being able to extend lifespan matters with pets. Simply because, I think last year or two years ago, was the first time that Americans spend more money on their pets than they did on babies. And millennials are having dogs instead of children. One study in 2018 shows there’s a high rate that Americans are spending on their pets than on food or medicine for themselves. So we are naturally more prepared to do something for our furry loved ones than we are for ourselves. Even when it comes to our health. And people will be willing to do anything to extend the life of a dog. And we had this small discussion before that when you get a dog, you do sign up for the joy of having that companionship, but that is very limited time. All of us would do anything to have them longer with us. So in terms of messaging and perception, it’s so crucial. Because if people see a dog living longer or that we did extend life, then it’s going to be very easy for people to believe “oh, then it could happen to us too?”. With that said, I wanted to ask you about going back to you explaining the rate of aging of dogs. Something like this seven years per year. You said that it’s not precise, but it’s very close. Can you tell us a bit more about that?

Matt Kaeberlein: Sure, absolutely. I think maybe the first thing to say is, going back to the original question, which is “how do you define aging?”. So I think part of the challenge here is, that we don’t have a consensus definition of biological aging in the field. And so given that, we don’t have quantitative ways to measure biological age or biological aging rate. And I’m going to take a second just to expand on that a little bit. Because, I think some of the people listening, the nuance there may not be obvious to them. So, we all understand chronological age. That’s just the length of time from when you were born, to where you are now. And your chronological life span is just the length of time from when you were born to when you die. The important point here is that biological age doesn’t necessarily have to match chronological age. If the biological processes that we are defining as aging, these hallmarks or pillars of aging, they happen at faster or slower rates in different individuals. That’s true in every animal that we know of. So the same 40 year old persons, or people to 40 year old’s, can have very different biological age. And we all know this. I think all of us have people in our own lives that biologically are older or younger than their chronological age. And typically that goes along with health. So if you look at dogs, they are really interesting because their biological aging rate is strongly determined by body size. So big dogs age faster biologically than small dogs. Small dogs will live longer. And for most diseases of aging, they develop those diseases of aging later on in life. So this is actually really good case example where the rate of biological aging is very obvious and very different across small dogs versus big dogs. Even though their chronological age can be the same. So this idea that one human year equals seven dog years is first of all not perfect across different body sizes in dogs. So that metric is going to be different in a Chihuahua versus a Great Dane. The other thing that’s imperfect about that metric is that it’s not linear. And what I mean by that is that early in life, dogs seem to age even a much more rapidly than a seven to one. Maybe it’s twelve to one or something like that. And then as they get older, their rate of aging relative to people becomes less than seven to one. And that’s still being worked out. So I don’t think we have, again, really good at quantitative ways to assess that. But it does seem to be the case that seven to one ratio is not going to hold across the entire lifespan. And it’s different early in life versus late in life. So it’s just more complicated than the simple idea that one human year equals seven dog years. But having said that, again, it’s pretty close. I think on average, that’s not a bad rule of thumb just to get the idea across that dogs age about seven times faster than people do, across their entire lifespan.

Avi Roy: Thank you for that, Matt. I want to actually dig deeper into what you were saying, because you came really close to biomarkers of aging. So going back to the Dog Aging Project, you pointed out that over the next few years you’re going to have a whole bunch of epidemiological data. And then you can also randomize this stuff and actually look at testing and collaboration. But really, testing is what you’re going to look into. So my question is, how are you measuring aging in your dog cohorts? And, so that you can actually ascertain what environmental affects they’re having, and what endpoints are you looking at?

Matt Kaeberlein: Yes, really good question. So let me start with the clinical trials. I think that’s easiest at least to start. So the primary endpoint is lifespan and the study is really designed to ask whether rapamycin can increase lifespan in middle-aged dogs with normal health status. That’d be larger dogs, as we just talked about big dogs age faster than small dogs. So that’s the primary endpoint. But then for secondary end points, we’re really trying to look as broadly as possible at age related outcomes. So all the dogs, for example, will get echocardiograms every six months to look at the cardiac function. Does rapamycin change or improve cardiac function with aging? We will be looking at activity. So the dogs will be fitted with activity monitors. We’ll be looking at disease incidents, cancer, kidney disease, dementia… Basically every age related disease that you can think of that dogs and people both get. So the idea is really to take a broad functional and disease based approach to assess “is this intervention actually impacting the aging process, functionally?”. And then we’ll also look at molecular markers. Every six months, at the time the dogs come in for their exams, we’ll collect blood for standard blood chemistry, blood metabolism, epigenome… And then we’ll also collect feces to look at the fecal microbiome. So, to try to get a little bit more of a systems biology perspective on what’s changing with age in dogs, and how does the intervention rapid mice in this case impact those molecular markers? We’re trying to be relatively agnostic with respect to the current sort of biomarkers that people in the field are most excited about. We’re not going in with the assumption that the epigenetic clock is going to be the single best measure of efficacy for interventions. We’re really going to try to let the study tell us whether that’s the case. I think this is a bigger challenge in the field right now. Just take a step back and talk a little bit more broadly. And in my view, too many people in the field have basically decided that epigenetic clocks are measuring biological age. And I think that’s a problem, because once you start looking under the lamppost, it’s really hard to stop looking under the lamppost and you miss a lot of important biology. And unfortunately, I feel like that’s what has happened in the field right now. Eventually it’ll get figured out, but I’m worried that we’re spending a ton of time looking at the epigenetic clocks and not looking at other stuff that might be equally or even more important than potentially diagnostic for aging rates.

Avi Roy: That’s fantastic. So like the NSA you’re basically collecting everything, and then whether now or in the future, you will figure out as to what we can use that data for and how much of that is actually useful.

Matt Kaeberlein: Although, let me just let me chime in for a second. Because yes, we’re trying to collect as much as we can. And obviously every study has constraints. We can’t collect everything, but we’re collecting as much as we can. But I also want to come back to the idea that this… And this is my personal sort of view on this, but I really feel that the functional measures are the important things to look at. So if we see that rapamycin makes dogs live longer and their hearts are working better, their kidneys are working better, they’re not getting dementia and they’re more active. But it doesn’t change the epigenetic clock. I’m not going to say the intervention didn’t work because it didn’t change the epigenetic clock. I’m going to say it worked and the clock is broken. And unfortunately, I think too often people take reverse view in the field right now. I don’t care if you change my epigenetic clock. I care if you make me live longer and healthier. And I think we need to get back to that a little bit.

Laura Minquini: Matt, I just wanted to quickly ask what do you think is equally or more important than the functional measure of the epigenetic clock, in your opinion? You’re saying you cannot use the epigenetic clock as the one measure that shows success. Unless you’ve mentioned right now, if you didn’t manage to reverse something, it is the outcome that matters. But what of the things you are looking at that you find is equally as important or maybe even more important?

Matt Kaeberlein: Okay, so that’s absolutely a fair question. So, I guess I would say that I’m not convinced that there’s anything better than the epigenetic clocks at this point, as a single sort of type of bio marker. And I didn’t mean to give that impression. I think that there’s a lot of data to support the idea that they’re going to be valuable. I think, where my concern lies, is that too many people have assumed is that anything that changes the epigenetic clock in a certain direction, is actually having the effect on biological aging that they wanted to have. So I’m not saying that there’s something better right now. I think what we really need to do though, is continue to develop other types of biomarkers so that we can actually, once we start to see how interventions affect functional outcomes and healthy longevity, we can figure out which are the most predictive. My intuition is that it’s going to be a combination of types of molecular markers. So these multi-omics clocks, so to speak that some people are thinking about. Which could include things like blood metabolite or metabolome changes. A subset of inflammatory biomarkers. And even maybe some morphological changes. So we haven’t looked at all at this in dogs, but there’s some pretty interesting data in humans that even changes in facial features, which we all recognize as a part of age. That those can even be predictive of health status, not just chronological age, but actually health status as we’re getting older. So if I had to guess, my guess is that it’s going to be a combination of these markers that will be most predictive and most useful. I think that the other sort of nuance point that is worth making here, is that a biomarker of aging in my view is not particularly useful unless it’s actionable. And what I mean by that is that, does it help you to know that your epigenetic clock says you’re thirty when your chronological age is seven. Is it useful? Maybe it’ll make you feel better, but it doesn’t really tell you what you should or shouldn’t be doing to impact your health outcomes going forward. What we really want, are biomarkers that are useful for predicting efficacy of interventions. And ultimately what we want to get to is as a personalized set of biomarkers. So we can actually personalize geroscience interventions, because I think we all should recognize that everybody’s genetics and environment is different and the sort of optimal dose of rapamycin or metformin or whatever your favorite aging intervention is for me, might be very different for you. And ultimately what we want to get to is the point where we can use these biomarkers to predict at a personalized level: what are the actionable things that you can do to give yourself the best opportunity for long healthy life?

Avi Roy: Thank you, Matt, for that. Everybody in the room, we will be opening it up for questions very soon. Laura and I just have a few more questions before we jump into audience questions. So hold on to your hats for a little bit longer. And just remember that this show is being recorded. Matt, continuing with that team, I just edited a quick question before I hand it over to Laura. And the second part is not necessary, but I’m just kind of tacking it on. Is there anything unique or unusual about the aging process in dogs, when we compare to other organisms? And can the findings of the Dog Aging Project, can we extrapolate the results towards human longevity and human aging, ultimately? Not that it is a necessary part of the dog aging process, as the conclusion of the dog aging process leading to longer life span of dogs, is in itself fantastic. But can we actually extrapolate from that? And is the dog aging process in any way shape unique compared to other elements?

Matt Kaeberlein: Sure. So the short and simple answer, is yes to both of those. But I’ll explain a little bit. I’ll start with the second question, which is, will anything we learn in dogs be relevant for humans? I think it’s clear that the biological aging process in dogs is quite similar to that of humans. I think even if you just look at the types of diseases that dogs get with age, it matches almost perfectly with the types of diseases that people get with the age. The functional declines, that go along with age. And even the little bit that we know about things that impact functional outcomes and lifespan in dogs also impact functional outcomes in lifespan in people. The two obvious ones being exercise and obesity. So it’s hard for me to say as a scientist, with a hundred percent certainty, that the biology of aging in dogs is identical. In fact, it’s not going to be identical to the biology of aging in people. But I think that everything we know, gives us confidence that much of the biology of aging in dogs is going to shared with people. And so I am equally confident that a lot of what we learn from the Dog Aging Project will be relevant to the biology of aging in people. Now, those are going to be hypothesis generating types of knowledge. So we may see a relationship between a particular gene or a particular environmental component in health outcomes in dogs, that we would then hypothesize will be relevant to people. Obviously that requires additional research to go and test that hypothesis. So certainly I’m not arguing that just because it works in dogs, it’s going to work in people. But I think it certainly gives us a degree of confidence. That’s probably the case. And we are others that can go on and test those things in people. Now, you asked if there are differences in dog aging versus human aging. And the answer of course is yes. And that’s true for any animal. There’s this older idea from George Martin, who is the grandfather of geroscience in a lot of ways, of public and private mechanisms of age. And I think it’s a really nice concept, that when you look across different species there are aspects of biological age in public that are shared maybe across all animals. And then there are aspects that are private to each species, depending on their unique genetic and environmental makeup. And how evolution shaped those animals. And yes, there are going to be public and private components of aging between dogs and people just like there are between people, mice and worms. So the key is to figure out which are which. And I think we’ve got a pretty good idea already within the field of that. Specifically in dogs, I can point to a couple of examples. So one example is that dogs don’t get a lot of vascular disease. When you think about cardiovascular disease, vascular disease with aging. Whereas obviously that’s a major killer of people. And they get a lot more cancer than people do with aging. So there are differences, at least in the disease presentation. Does that mean their molecular differences or is it just because of the unique features of dogs and people that the way those molecular agent processes manifest themselves as functional declines in diseases are different? I think we don’t know. The other area that I’m really interested in right now, is cognitive function and cognitive changes with aging. So just like people, dogs show cognitive decline with aging. A subset of dogs will go on and get dementia. That dementia looks a little bit like Alzheimer’s disease. And so that’s really interesting. And we’ve got an active and expanding project to look at dementia in dogs. The thing that I’m most fascinated with, is at least the initial indications there are that this body size relationship I talked about before, big dogs live shorter and appear to age faster than small dogs, that seems to be true for lots and lots of different age related diseases and functional declines. At least the preliminary data suggests that might not be true for body size. In other words, and this is preliminary, but big dogs may not actually show signs of cognitive decline and dementia any faster than small dogs do. So that might actually suggest that there’s something special about the brain and the relationship between body size and aging. That’s a, long-winded answer to your question. Yes, there are differences, but I don’t think those differences are so big that it’s going to limit the information that we get about potential causes of human aging.

Laura Minquini: Thank you, Matt. I am going to ask, specific about the Dog Aging Project, where are you at with it? And can people still enroll their dogs? I know that it is only in the US for now. And I have a question. When you are looking at enrolling the dogs over the assessment, you’re looking at different breeds and different stages of life, but are you also looking at the environment that the dogs are living in? Are they living with professionals? And what are their owners? Do they live in the city or do they live in the country side? What’s their socio-economic status, race… Are they having any barriers on your studies right now?

Matt Kaeberlein: Sure. All good questions. So I’ll start with: are we still enrolling dogs? The answer is yes. And I absolutely encouraged any of you who are interested in participating to go to dogagingproject.org and nominate your dog. It’s a super simple process. Three or four questions. And then once you do that, you will be invited to create an owner portal within the website, where you will then be asked to complete what we call the health and life experiences survey. And that is basically to address the question, Laura, that you just asked. To get the data on the dog’s health history, its environment, activity levels, diet… Basically capture as much information about the dog and its home environment, as we possibly can. And that’s a huge amount of data that we’ve already collected, which I think of it as the tip of the iceberg because we just started analyzing. But yes, absolutely. What you asked to answer as we try to capture as much information as possible through this health and life experiences survey. We also have a cognitive survey, which will give a feel of cognitive function in the dogs, that the owners will be asked to complete at the same time. At that time, once they complete the health and life experiences survey, they are also asked to send us the electronic veterinary medical records. And that can come from the owners or from the veterinarian. And the pairing of those two things gives us a really unique insight into current health status, prior health status and all of these environmental variables that we capture in the survey. And that’s the base group in the Dog Aging Project, what we call the pack. The Dog Aging Project Pack. You have people who have completed the health and life experiences survey, and then invited to send us their electronic medical records. So that brings me now to, where are we now? So we have spent the last two and a half years basically building this machine to do the science of the Dog Aging Project. So, we’ve created the infrastructure. And anybody who has ever been involved in a big science data project will understand how immense the challenges are just on the data side for building the infrastructure to do what we want to do.

[00:37:24] And then we’ve also set up the clinical component of the Dog Aging Project. So the way this works is: there are right now 32,000 dogs in the pack. A little bit more than that, actually. So this is already pretty large longitudinal study. All of those dogs in the pack are a longitudinal study agent. So 32,000 plus dogs. My goal was to get that up over a hundred thousand. I think that’s doable. From the pack right now, we are funded to select 10,000 dogs for genome sequencing, to become what we call part of the foundation cohort. So the owners will have it shipped to them where they swab their dog’s mouth to collect cells. And then it comes back to us for genome sequencing. So that’s the genetics part of the Dog Aging Project. For 10,000 dogs in the pack, we’ll have full genome sequencing. And then a thousand dogs are selected for what we call the precision cohort. That’s the systems biology cohort. So every year, those dogs will go to their veterinarian and they’ll take a sample kit that we send them to the veterinarian and we’ll collect along with the veterinary exam blood chemistry, blood for a certain microbiome, feces for metabolome and feces for fecal micro biome and blood epigenome. So we’ll get those three sort of omics types of data for a thousand dogs every year in precision cohort. And obviously this will be done on an annual basis. So over time we’ll be able to see how are those things are changing as these dogs age and match that up with their genetic and environmental data. And then there’s the clinical trial. So that’s triad. So for the other cohorts, any dogs, any size, any breed, any age… So it’s really open to all dogs. For triad, the rapamycin clinical trial, dogs have to be at least seven years old and between 40 and 100 pounds to be eligible for triad. They also can’t have a pre-existing age related disease. So this is a clinical trial of helping agents, really in my knowledge, the first and only true clinical trial of healthy aging in dogs. And the goal as I’ve already talked about, is to determine whether rapamycin can slow aging in dogs. So we’re selecting 350 dogs right now. We’re funded to bring it up to 500. They may come in for their initial visit, because some of those dogs will be excluded based on pre-existing conditions. So 350 will be randomized, half of the placebo group and half of the rapamycin group. It’s a one year treatment period. Then two years of follow-up. So three year total clinical trial with lifespan as I’ve already talked about. So those dogs would come in every six months. So that’s the big picture overview of the Dog Aging Project and where we’re at now. We just had the first few thousand dogs from the pack reached their one year anniversary. So the owners every year are asked to update the health and life experiences and cognitive surveys on an annual basis. So we now shifted from being a cross-sectional study, one time point per animal, to a longitudinal study, where we’re now starting to collect data on the same animals spread out over time, every year.

[00:40:44] And so that’s super exciting and we’re just now digging into the data from HLAS. And all I can tell you right now, is that it’s super interesting and exciting. We’ve already found some unexpected things, that I think are going to be really neat. And then we’ve also invited a few thousand dogs to foundation for genome sequencing and a few hundred dogs to precision. And we anticipate fully enrolling those cohorts triad. We’ve had the first dogs now scheduled for their screening appointment. And I think we’ll have the first dogs randomized into try out, within the next couple of months. So, we’re not as far along as we hoped we would be two and a half years ago. But I think given everything that’s been going on in the world for the last 18 months, we’re in a pretty good spot. And honestly, I’m just really happy with where we’re at and the potential that I see for what’s going to happen over the next few years.

[00:41:40] Laura Minquini: Yes, I watched a video where you mentioned that it was difficult. You can’t ask the owners to be bringing their dogs to tests while we’re in the middle of a pandemic. It happened and it’s taking into consideration anything that’s been done. And I can’t wait until you go global or at least to Canada, because I’d love for my dog. I keep messaging Avi saying “I need to start doing all of this for my dog!”.

Matt Kaeberlein: Yes, that’s probably one of the top things on my list that I would like to see us do, is be able to go truly international. There are some logistical challenges with that, but honestly, right now it’s all about money. We’re constrained in what we can do, just with the grant that we’ve got. If there’s anybody on this call or anybody that knows somebody who would like to donate to the project to make it an international project, I would love to see that happen. So I’ll just throw that out there on the off chance if somebody is listening.

Laura Minquini: I feel that Nathan, who’s in the call, will figure out something for you as he’s the expert of that. Everybody has come to ask questions, I’m going to ask Matt one last question before I start to bring people up. Feel free to ask your question as well. I wanted to ask you because you have a dog named Dobby, right? What breed is it again?

Matt Kaeberlein: He is a German Shepherd.

[00:43:02] Laura Minquini: It’s very simple for the consumer, because I know people always ask about their own health. What is your longevity protocol for Dobby?

Matt Kaeberlein: So that’s a good question. So again, I’m going to first of all say what I said at the beginning, which is that I’m not a veterinarian. So nothing that I say should be considered as veterinary advice. Honestly, it’s funny because obviously I get asked this question a lot by almost anybody who works in this field in talks to the general public. In some ways, it’s a little bit disappointing. My answer is going to be a little bit disappointing, because this is nothing that you wouldn’t expect. Dobby is at appropriate weight for his breed. He might even be a little bit underweight. We take him for walks at least twice a day. We take him to the veterinarian on a regular basis. We give him lots of love. Honestly, I think that’s probably one of the most important things. There’s a lot of interesting data that interactions between owners and dogs have important physiological effects on both the owners and the dogs. And I think giving your dog lots of love is great health span promoting strategy, but I honestly can’t tell you that there’s any particular supplement or intervention that I recommend people giving them at this point. The one thing I would say is, there’s a lot of people out there who have very strong opinions on diet in dogs. And you can find people who will swear up and down that a particular diet is the best diet for healthy longevity in dogs. The one thing I would say is there’s not much data to actually support those strongly held opinions for a particular diet in dogs. And that’s something that I hope that will come out of the Dog Aging Project in the next few years. It’ll be correlative at this point. There’s a real correlation between diet and other environmental components. And health outcomes and disease in dogs actually give some data. I do think it’s important though to explicitly state that at least from the longitudinal study, those are going to be correlations. And correlation does not equal causation. So while I think we’ll be able to say, dogs that eat a particular diet or maybe even a particular brand of dog food tend to live longer or shorter, be healthier, more or less healthy. It’s still not going to be proof that those interventions or those dietary changes have an effect on longevity. That’s the difference between the longitudinal study and a clinical trial. If we see that rapamycin treatment hits and points, whether it’s lifespan or heart function or activity or cognitive function or whatever, then we’ll have a pretty good case that there is a causal effect from that intervention and the outcome. Because it’s a double blind, randomized, placebo controlled clinical trial.

Laura Minquini: Thanks, Matt. I know we all want something magical, but even for dogs, there isn’t such…

Matt Kaeberlein: Yeah, no. I try not to use the word magical, because that has the connotation of … I know what you mean, but I try really hard not to do that because I think, sometimes, we want to get away from the idea that changing the biology of aging is something other than rigorous hard science, because it is rigorous hard science.

We would like to say a huge thank you to all of the panelists for giving us a portion of their busy schedules, and providing such an enlightening and thoroughly fascinating conversation. Our thanks also goes out to the hosts who cultivated such a fantastic discussion!