K9 Longevity is presented by Myios Pet, the leaders in pet muscle health. Hi, I'm Dr. Sherman Kap with K9 Longevity and I am extremely honored to have Dr. Nicole Erhard. She is the director of longevity at Colorado State
University and this program is translational. They look at aging in humans as well as animals. Dr. Hart, it is a honor to have you here today. >> Thank you for having me. >> So, I know you as the worldrenowned surgeon, oncological surgeon, oncology,
all things cancer worldwide, and I'm starting to notice this change as I'm looking into your research and your publications and your work and this whole area of regenerative medicine and then translational medicine as far as aging's concerned and your director position at Colorado State. Can you tell
me how did that path begin and where are you now? >> All right, great question. Um, a common question. So, uh, a lot of the work I was doing in regenerative medicine was looking at acute defects. So, these large muscular skeletal defects and how we can regenerate tissue in areas where
we've exceeded our generation regeneration capacity such as large muscle and bone defects. And then it kind of occurred to me I did an a sobatical in 2018 at the Stemman and Philippon Research Institute and had the opportunity to work with master athletes
um who are these incredible you know people over the age of 60 who are running like 100 mile marathons and and other you know incredible feats. And I was collecting stem cells from their muscle as they were having various different types of surgeries and recognized that their stem cells were
extremely robust as compared to other people that were their age that were sedentary. And I really started to get the light bulb that perhaps some of the treatments that we've been using to regenerate tissue and acute defects could be repurposed to think about this
as a chronic situation and and regenerate or rejuvenate tissues that have been deteriorating or degenerating over time. And that sort of leapt me into the whole longevity field and it was like a perfect match. So it's been
an amazing amazing journey >> and I see a lot of your work says this term onehealth. Is that a translational term or help me understand the one health term that you use? >> Yeah, I mean we share the planet with these four-legged creatures and other creatures and um they live in our environments and they are part of our
everyday life and you know it's important that we think about this as a paired situation. A lot of times the animals that share our environments are sentinels for our own aging pathways. they're exposed to the same things that we are. And not only that, they have a shorter lifespan than we do. So many of
the interventions that we might use to improve health span and longevity in humans can be studied in companion animals and other animal species in order to um in a shorter period of time in order to see if they're efficacious or not. And so why not use that as a
two-way street, right? What can help us can also help our pets and vice versa. >> So you speak of efficacy. Have you seen or can you share with us some of the significant findings you've had clinically or from a even from a benchtop research standpoint? >> Sure. I mean we are in early stage research with a lot of these things. Um
and the idea is to translate this into intervention trials in companion animals that then will inform human medicine and the idea is really to accelerate and derisk these longevity and health span interventions. And so a lot of the work that we're doing is in the stem cell
world, which shouldn't surprise you if you know I've been involved with regenerative medicine all these years. The main thrust of our research is in something called extracellular vesicles or exoomes. And these are the things that that the stem cells secrete in order to create their biologic effects.
>> So do you feel or have you seen then that we can take the exoomes so the stem cells are releasing them? Is there a way that we concentrate them or how does that work as far as having a clinical application? >> Right. So the parent cell line in the case of the research I do are the
messenal stem cells and they're cultured outside the body and then we collect the supernated or the culture media that in in which these exoomes are secreted by the uh MSC's then we concentrate those down using a process called ultra
centrification then we can count them and know how many are in there and then our research has been looking at what is the cargo content and can we optimize the cargo for specific ific applications, things like muscle loss or tendon healing or bone healing and the
conditions of the parent cells and the type of parent cells that you use actually influence the cargo that is within the exoome so it's tunable you can actually tune it for specific applications. >> So then would the idea be that you can concentrate this down? Would you be able
to keep it say in cryo or keep it preserved somehow and then as needed you would be able to dose that out and is it to the same patient or would you be able to use that to other patients? Of course that has to go down the FDA line but is that something you're looking into? >> Yeah. So um one of the advantages of doing the exoomes or extracellular
vesicles over a cellular therapy is that they can be frozen and they remain relatively stable when frozen for long periods of time. There's even evidence that they can be freezedried, which would be great because then you don't need cold chain storage and you could ship anywhere. Um, and also because
these can be donor cells and they're nonimmunogenic when they're formed. So these exoomes themselves don't create an immune response, a donor can be used to treat multiple different patients rather than the individual patient donating back to themselves. And so yes, there are all the regulatory pathways that we
have to navigate, but the promise here is that we can have an off-the-shelf product that could be widely clinical applicable clinically applicable to a number of different disease states and a number of different patients. >> So I have to ask you because you're dealing with aging longevity. There's this theory or hypothesis I would say
that dogs age at this 1 to seven. You know, we always say oh one year in people life is seven years in dog life or maybe it's different in small breeds versus giant breeds. Is there any truth to that or is there anything you've looked at? I know it's translational, so you'll get a human in animals, but what can you tell me about that? >> Well, I haven't looked at that personally, but there's been some very
eloquent research done in that area and specifically they're looking at methylation clocks or the little tags on our DNA that help that change as we age. And the person that's done probably the most work in in comparing animal, specifically dog age, to human, is a guy
named Trey Idker. and he published a study that got a ton of press and I think it was I don't know four or five years ago looking at the age um comparison between humans and dogs based upon this methylome or these DNA tags that they can measure and it turns out that it's not exactly 1 to 7 there's an
exponential curve that changes but we do know that dogs go through all the same developmental phases as people and we know what ages those are you know infancy adolescence adulthood senior you know life and so we have scales that we can actually apply that are really
applicable from the standpoint of the methylation and the biologic aging of the of the species that we're interested in. In this case, dogs. >> K9 Longevity is presented by Myios Pet, the leaders in pet muscle health.
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while reducing muscle breakdown. With over a decade of research and real results because stronger muscles means more moments together. My more time together. biomarkers. So some of the work I think
you've been doing is on biomarkers. I know there's so much out there right now as far you know inflammation, gut inflammation and GI mapping um and even its effect not only on aging but cognitive function with with you know inflammation and markers. >> What are you doing in the world of of biomarkers? Is that something you're
looking at within your your studies? >> We are we're really interested in this whole idea of the peripheral central communication and brain health and what affects brain health. For example, we know that certain lifelong interventions like exercise and good sleep are related to longevity and healthy aging in
people, right? Um, and for a long time, we weren't really sure how that happened. We also know that exercise is preventative or protective against cognitive decline in people. And the dog aging project has shown the same thing in dogs. So, there's something about the periphery that happens during exercise
as an example of one intervention that impacts our central nervous system. And so what we've been looking at are the exoomes that circulate in our blood that happen after we exercise and how those are actually dampening inflammation within the bl brain both in induced
inflammatory models as well as like natural aging models like the dog and we have certain other animal models like guinea pig and other where we know those naturally age and they develop cognitive decline over time and we can intercede with different exoome interventions. >> Wow. There's also something I've I've
read about in your lab. It's the human dog bioank I believe it is. Um can you can you explain that? >> Yeah. So we're really interested in the idea that the animals that share our environments are actually sentinels of our own aging pathway because of their exposures and because they're also you
know impacted by our lifestyle choices like our you know exercise and active lifestyle versus secondary or sedentary lifestyle or secondhand smoke or other things like that. And so the idea there is to actually have human dog pairs living in the same household that are
providing biopecimen samples over years at a time and pair that with metadata from their medical records to understand what exposures and environmental impacts and even social impacts have on our own aging pathway. And we believe that by
looking at changes that might happen in the dog, we can actually preempt or detect changes that might be happening in the human that's living with that dog. And so that's a unique part of the bioank idea is to have the diads or the pairs together. And I don't think that exists anywhere else in the world.
>> No. You spoke before about the exoomes and how we can concentrate those down and keep them in cryo. Let's talk about stem cells. So the stem cells age as we age, I believe. Is that is that correct? And so is there any thoughts then if that's the case that you would collect
tissues from dogs when they're young >> and process placing cryo so that years down the road when they're older 10 years of age they don't have the 10-year-old stem cells they have their young dog stem cells >> and does that mean that they'd be a little bit more potent as far as tissue healing or regeneration? Um explain
that. Is that something we should be considering clinically or >> I mean it's a good idea. That's kind of the idea behind cord blood that's collected when a baby's born is that you'll have that forever and that that person will never be that age as an infant again, right? And we do know that our stem cell pool diminishes over time
um as we age and their robustness of the of the stem cells that exist also diminish. So in theory, it makes sense to bank stem cells earlier. I think we're starting to get over that hump where we may not need to bank them as much as we may we be we may be able to
genetically reprogram stem cells even late in life to behave more like young stem cells. And then the other thing we've been working on in our lab is actually exercising those stem cells outside the body. So creating an ex exercise mimetic we call it in a
bioreactor and then collecting the exoomes from those um that actually have the same content as a younger animal or younger person and developing therapeutics out of that. So we talk about the pillars of longevity and aging, exercise, nutrition, cognitive
function, you know, cognitive wellness is a huge part of that. And I looked further into your into your research into your lab and you have a psychologist, I believe, on your board as well. Um, what type of work are you doing looking at cognitive function and and specifically in dogs? >> Right. So we're looking at different
interventions both lifestyle interventions and therapeutic interventions that may impact cognitive health as we get older and also looking at different nuanced ways to measure cognitive health and biomarkers of cognitive health. So our psychologist is a person who's an expert in uh
neurodeenerative diseases. She's a neuroscience scientist and she does a lot of work in dementia. Um she's also someone who runs a center called the aging center of the Rockies which is a uh a center that does neurosych evaluations on people. So again nuanced
ways of actually diagnosing cognitive decline when it's early and then um intervening. And then we're trying to utilize the same types of measurements um that are proxies for similar types of behaviors in dogs. And you know, there's many assessment scales that are used for
cognitive um decline in dogs, and those are are very validated and good assessments. We're trying to add to the body of that literature and then pair that with biomarker changes where we can see over time changes in um cognitive health and actually ex uh intercede
early enough that we can maybe prevent uh rapid decline or further decline. >> Oh. So, in your lab, what's next? What's your next steps or what's the next studies or research that you're looking into? what's kind of the hot thing that you're going to be diving into? >> Yeah, I mean I think there's so much
parallel work going uh on uh looking at different interventions that one of the things I think we need to advocate for broadly is the idea of creating a very well um designed infrastructure for clinical trials for longevity interventions in companion animals and
utilize that again to inform human health to accelerate and derisk some of the um some of the newer studies. So thinking about ways in which we can add to the body of science which is huge in the rodent and other pre-clinical models but really has failed to translate very
rapidly into people and I think the dog is the bridge. I really think that if we can create a a very well-designed infrastructure that's multi-institutional that we can perform these kind of compliance studies, GCP compliance studies that are uh
multi-institutional, that are placeboc controlled and double blind, we can probably move the needle much faster. So that's the kind of thing I really want to develop uh from the standpoint of clinical translation. And in the lab, we're continuing to develop other things like other exoome based therapeutics as
well as different interventions that improve longevity um and cognitive health. >> This segment of K9 longevity is brought to you by Equisir for dogs, combining light therapy, infrared, and neuro stimulation to help support K9 comfort and movement.
you're looking at biomarkers and looking at something where we have metrics that we can look at translationally and look at other universities and having those would allow us then to look at other medications or drugs that are out there. We talk about metformin. We talk about rapamyosin. It would be nice if we had
those objective outcome measures that then we could look at all those different types of products that they're looking at for humans and start applying those to dogs of which have you done any work with rapomy in dogs or do you know anything about should that be something that >> I believe there's some studies the dog
aging project I believe is one of them. Um can you say anything about rapamyosin for dogs? >> Right. And I haven't done any studies personally with rapamy in dogs, but I think the triad study and the dog aging project is the most active one currently and they are currently enrolling. Um I think that there are a number of
different other um studies that could be done in in different um populations. I'm very interested in the cancer population. I'm particularly interested in how treatment with chemotherapy actually accelerates aging. We know this in people. Um we can see it. We can
observe it in people. Um, and we believe that also happens in dogs. And so we can look at some of these longevity uh interventions that might target for example scinesscent cell burden or other things that may actually impact cancer outcomes. So if we can rejuvenate the
immune system and prevent a lot of scinessence buildup in the immune system um perhaps we can actually have better outcomes with our cancer treatments in our pets as well and then of course in humans. So that's another area of research I'm super interested in. Um, I haven't done any specific work on rapammy, but that would be a therapeutic
agent, that would make a ton of sense. >> Yeah, completely. >> So, if you were going to say to any of the pet parents that are out there, anything they could do to help currently or in the future with the wellness, longevity, health span of their particular pet, give some advice, give some give some recommendations on things
that you just think would be easy that they could consider straight away. >> Sure. >> For their pet. Well, we know across all species that have been studied that keeping a lean body mass is important for healthy longevity. We also know that in dogs, at least based on the dog aging project observations, that having
another dog in the household is generally a really uh healthpromoting thing into old age. Um and then of course um exercise, active um so those are just interventions that I think anyone can do. It's not easy to calorically restrict your dog all its
life, especially if you have a Labrador, which I have too, so trust me, I know. Um, but uh, but the type of things that we can actually mimic caloric restriction with certain therapeutics, those are things that I think are going to come online in the near future. So, as a pet parent, what I would do is stay
informed about longevity trials that might be available to you in your location. Um, keep uh in tune with the media and um, scientific literature. ask your veterinarians about this because I think so much is coming online that will really impact the health and longevity
of our pets uh in the near future. And so we're starting to see this explode. It's a very exciting area of research and I think I love what you're doing. I'm excited that you're asking these questions and I hope that pet parents can continue to stay informed through both through this program and you know
keeping in touch with scientists like myself who are working at the front lines. >> Dr. hard. Can you share any clinical cases or anything that comes to mind on a case, we'll call it a successful case that really you remember? >> Sure. >> As as it relates to say regenerative medicine,
>> right? Yeah. I mean, a lot of the work that we did early on was in limb salvage, right? And this is where you have to remove a large portion of bone usually or sometimes bone and muscle and you're trying to get that area to heal. Um, some of the things that we've used to heal the area are things like bone
grafts and even implants. And one of the areas that was a really exciting area where I felt like we really made some progress was in looking at um the integration of these implants with the parent bone. And so we started thinking more along the lines of the biology of the patient. And you know instead of
creating better and better mechanical parts that fit better or function better, how do we harness the biology of the patient? And so we started with stem cells um and in a particular patient this dog had a osteocaroma. We also wanted to make sure that it was safe to give stem cells to a dog with osteio
saroma. And it turns out that we did a bunch of mouse work and and looked at that very carefully and we felt that it was safe. And this particular patient, the owner was really willing to go the extra mile to hope that this dog would heal. And we used stem cells to help his limb salvage um implant actually
integrate with his um his parent bone. And that dog was one of the few successes I've had. Now, that's an N equals one. I'm not going to try to tell you that this is going to be a treatment that will work for everyone. And certainly, we've looked at different ways that we can optimize that and and tweak that. Um, but you know, these are
the kinds of people that are looking for something, a solution, that are willing to go the extra mile, that are willing to be part of something that's on the cutting edge. And those are exciting times for us because we get a chance to really see if what we're seeing in the laboratory is really going to work in real life. And there's been a lot of
progress in that area. We talked about the limitations of stem cells. I think the extracellular vesicles or exoomes will behave the same way and yet they're so much easier to work with. So that's probably our next step. Um and again getting that into our patients is the most important part of this. The science
is great. We can learn a lot about that, but until it becomes a real world treatment or a real world benefit to those animals, it doesn't really ever have the impact that we're really looking for. And as a clinician scientist, that's what our work is really all about. >> You know, I think that's a great example of allowing the body to help heal
itself. >> That's right, >> Dr. I'm so excited about what you're doing and so fascinated on the the lab, everything you have so far. I'm I'm just dying to continue to follow you. >> Thanks. >> This is Dr. Charman Canap with K9 Longevity. Remember, it's all about K9
health span, not just lifespan. Good girl, Fachi. K9 Longevity is presented by Myios Pet, the leaders in pet muscle health.