Brad Younggren: Filtering Out Aging

What if removing and replacing part of your blood could turn back some of the measurable signs of aging? Brianna Stubbs talks with Dr. Brad Younggren — emergency physician, former Army doctor, and CEO of Circulate Health — about therapeutic plasma exchange (TPE). They cover how the procedure works, what the blinded Circulate trial found (including an average 2.6-year reduction in biological age over three months), TPE's unique potential to clear microplastics from the bloodstream, and the broader impact of our environment—the exposome—on human healthspan.

Brad Younggren, MD, is CEO and co-founder of Circulate Health, a company dedicated to improving human healthspan. A former U.S. Army physician, Dr. Younggren served as a combat physician in Iraq and was awarded a Bronze Star and Combat Medical Badge. An emergency medicine specialist and seasoned healthcare executive, Younggren has led teams at the cutting edge of medicine for decades. Most recently, he was President and Chief Medical Officer at 98point6, where he led the development and launch of AI-powered primary care solutions. He previously served as Chief Medical Officer at Cue Health, Shift Labs, and Mobisante. At Circulate, Younggren leads an expert team of clinicians and scientists working to harness the potential of therapeutic plasma exchange to advance health and longevity.

Transcript

Brianna Stubbs 0:00

This episode is presented by Ashton Thomas Private Wealth, guiding families and institutions with clarity today and strength that endures for generations.

Brad Younggren 0:10

There's all this new exciting technology coming out. So I think like what we do for patients five years from now will likely be different than it is today because we'll continue to gain insights and understandings of how to bring new technologies into the clinics, which are impacting not only the longevity of patients, but their quality of lives.

Eric Verdin 0:29

Aging is evolving. No longer are we subject to forces beyond our understanding and control. We have charted the landscape and explored the frontiers of aging.

Brianna Stubbs 0:40

What was science fiction is close to becoming reality. Restoring sight, repairing tissues, reviving cells, organs, and maybe even a mind.

Eric Verdin 0:49

I'm Eric Verdin, CEO of the Buck Institute. And I'm Brianna Stubbs, a scientist here at Buck. In this podcast, we dive deep into geroscience, studying the intersection of aging and disease with some of the brightest scientific stars on the planet.

Brianna Stubbs 1:04

Join us because...

Eric Verdin 1:06

We're not getting any younger... yet.

Brianna Stubbs 1:07

Hello, Eric. How are you today? Not well.

Eric Verdin 1:16

No, I'm okay. Actually, I'm nursing the end of a cold. So that's that's why my voice is like this.

Brianna Stubbs 1:22

Immunologists aren't meant to get sick. You study viruses, surely that means you know how to like fight them off.

Eric Verdin 1:26

It goes both ways. One of the sayings is that as a virologist, actually we know them better, but they also take revenge on us.

Brianna Stubbs 1:34

I see, I see. Well, you've been you've been beating down viruses for enough of your career that it's really come for you this time around. So I had a really interesting podcast conversation in recently with Brad Younggren, um, who's one of the, well, he's leading one of the companies pioneering total plasma exchange TPE. I believe you wrote a uh paper with him recently.

Eric Verdin 1:54

I mean, full disclosure, I'm I'm a little conflicted here in a way that I'm I'm a founder on that company.

Brianna Stubbs 1:59

Okay, okay.

Eric Verdin 2:00

So um, but you know, the reason I became a founder is that I really believed in the biology, and and so we've been working with them together doing the first uh clinical trial of therapeutic plasma exchange. And so this is all the work that's based on on the idea that there are good factors present in young blood and bad factors present in old blood, and that therapeutic plasma exchange is a way to remove all these age-associated factors and hopefully lead to a rejuvenation. And this is actually what we saw in in two or three treatments in humans. We saw some picture, some signature of some partial rejuvenation.

Brianna Stubbs 2:41

Yeah, I um learned a lot talking with Brad. It was interesting because he came from a medical background but hadn't had a long career in the aging and longevity space. I think he was um in the military originally and had this very matter-of-fact, science-driven approach that you know I connected with a lot as a scientist and um was impressed to learn more about the company, how rigorously they're looking at both getting the treatment to people now, but also building the science around it as well. So hopefully the listeners will also enjoy learning more about Brad and uh TPE as an intervention for aging.

Eric Verdin 3:12

I agree. It's really of all the interventions, you know, there is a whole sort of nether world in biological research on aging, with lots of things being proposed, supplements, interventions, and so on. There's very little testing. And in some way, I celebrate the idea of taking each of these interventions, modification, lifestyle, supplements, is going to have to go through the same kind of rigorous uh uh testing, providing evidence so that when people jump into something and decide, this is what I'm gonna try, they know that it's been rigorously tested.

Brianna Stubbs 3:48

Yeah, and that's what we're trying to do here with the clinical research program at the Buck, and it's really great to see that there are others on that journey with us.

Eric Verdin 3:54

I really like Brad. He's totally aligned with what we're trying to do, and I hope uh our audience will enjoy the conversation you had with him.

Brianna Stubbs 4:12

Thank you so much for taking time to chat today. Um, why not at the very, very top of our conversation talk readers through um TPE, what that stands for, um, and and why you're interested in it over at Circulate.

Brad Younggren 4:26

Yeah, TPE stands for uh therapeutic plasma exchange. To put it simply, what we're doing through this procedure is to take out a percentage of someone's plasma. Now we use essentially a machine which is a fancy centrifuge with a computer to put it sort of bluntly, but then that allows us to separate the blood into its main components. And the plasma exchange comes from the fact that we're taking out plasma and replacing it with a substance that could be uh generally speaking, normal saline or a substance called albumin. We tend to use albumin in our procedures. And so that is the fundamental procedure that we did the human trial on, which is now referred to as the circulated trial, and as really the foundation for the business initially.

Brianna Stubbs 5:11

Can you just explain the difference between dialysis and TPE? Because you know, you're hooked up to a machine, stuff's going out, stuff's coming back in, just so just so we're all level set on the differences between that procedure, which people might be a bit more familiar with.

Brad Younggren 5:25

Dialysis is a fundamentally different machine. Um, it uses absorption, and you're, you know, obviously you're trying to take out certain substances which are built up in the body that for patients that can't use the kidney to, you know, as a standard filtration system. So fundamentally a different process. Um plasma exchange, or more broadly plasmaphoresis, has a number of different kinds of procedures. We use therapeutic plasma exchange, which is essentially removing the plasma from the body.

Brianna Stubbs 5:53

So if I come into a clinic um where I'm gonna be going and getting TPE, um, talk me through what my experience as a as a patient is gonna be like. I'm imagining I'm getting a big needle in one arm, both arms, and then um, you know, my my blood comes, my whole blood comes out, something's happening in a machine, and then something's coming back. So what and how long does it take? Um what are the sort of things that people would experience as they go through TPE?

Brad Younggren 6:20

Yeah, I mean, we're trying to create a very positive, calm experience for patients as we learn how to really build a broad-based outpatient system. And so obviously, there's a bunch of things that happen before the patient shows up that day: pre-screening, medical history, labs, things to ensure that the patient can safely undergo the procedure. But that aside, when the patient shows up and all of that work has already been done to ensure the safety of the patient, um, they're gonna come and sit usually in a chair, and they get typically two IVs. The reason two IVs typically will allow the procedure to occur faster because the blood is coming out of one arm and then returning in the other in the other arm. So you can actually do the procedure with just one point of venous access, where, but it just takes longer, as you can imagine, because you're effluxing and then returning the blood through the same line. So to complete the holistic procedure typically is going to extend the time it takes to complete the procedure. Um, as far as your question about how long the procedure lasts, it's typically between two and three hours on average. It's a weight-based calculation. So it is a bit variable based on size.

Brianna Stubbs 7:29

Once the blood goes out of one arm, you mentioned that there's a machine that's um removing the plasma, replacing it with um saline or or albumin. Um what is the hypothesis for what is in the plasma that you're taking out as to why it would be good to take that stuff out and not put it back in?

Brad Younggren 7:50

A lot of the thesis behind doing the circulate trial in the first place was based on the the many years of studies by uh the convoys and others at uh Berkeley, in that case, um, around this heterochromic parabiosis work, right? And so for the listeners who aren't aware of it, obviously I simplify it quite a bit, so apologies on that. But just for the perspective of getting through a very complex set of sites in a short period of time, hooking up the circulatory systems of genetically similar rats, one being old, one being young, and seeing sort of evidence of cellular rejuvenation in the old rat, and similarly seeing evidence of aging in the younger rat through that sort of mixing of the blood.

Brianna Stubbs 8:32

Earlier in the season, we actually interviewed Tony Wiskoray, who was involved with pioneering that work. So hopefully our listeners will have a bit of a primer and not be too immediately weirded out by the idea of these two little rodents sharing a circulation and wandering around attached to one another. But, you know, actually good for one of them, less good for the for the other one of them.

Brad Younggren 8:50

True, true. Well, I'm glad that you've already covered that. It's great. So we can so based on that though, the idea and the thesis behind putting together the circulate trial was we know there's a bunch of um components of the of inflammaging which exist in the plasma that that we believe impact um cellular rejuvenation or aging, depending how you're looking at it. And the idea was instead of focusing on a specific peptide or molecule as like the one thing we would do to impact aging, which there are many other companies that are pursuing these kinds of molecules. Um, the idea was, well, if we take out uh plasma from the body that has many of these components that we are concerned about, could we see evidence of cellular rejuvenation from simply executing on a protocol of plasma exchange with albumin replacement? And that's what the circulate trial did for the most part. We also had an arm that had IVIG, which we can get into as well. But in general, the idea was let's replace uh plasma from the body with human-derived albumin and see what the impact is on a variety of different objective measures and laboratory values.

Brianna Stubbs 10:07

So you mentioned the trial a couple of times. I um co-direct our clinical research um efforts here at the Buck. And um, one of the things that most impressed me about your study was your commitment to keeping the study fully blinded. So um maybe you can talk a little bit about why it's so important that we keep research blinded, um, research like this, and how you did it in the circulate trial.

Brad Younggren 10:28

So there were three different arms with a variety of protocols. There were actually patients who got therapeutic plasma exchange, and we can get into the some of those details as relevant. Um, but then we had a sham arm, and it basically the patients had blood drawn out of a line, and then the machine was essentially always behind a big drape, and the machine could be turned on, whether or not it actually is functionally working. So um patients were blinded to that, whether they were getting what we called phoresis versus sham phresis, and that allowed us to get a set of data that essentially was a control, which really provided a lot of comparator information when we actually went ahead and published the uh paper.

Brianna Stubbs 11:09

Did you see any interesting benefits in the control group to just you know being having the sham procedure?

Brad Younggren 11:15

When I first looked at the data, uh what it was stark to me was that you know, all three protocols where the plasma exchange was performed had had benefit, varying degrees, but all had benefit, and we can get into those details. But we saw the reverse effect. And in other words, patients had increase in biological ages in the sham group over those six months of sort of living life without TP, which I thought was sort of fascinating. I would have probably expected a little bit honestly less of a finding there, but um that it wouldn't be as profound as we actually saw. But nonetheless, that is what we saw. So we reported it.

Brianna Stubbs 11:48

I almost wonder if people in the sham arm were getting worse over the study duration, whether it was because they were coming in and having these more like, you know, medical procedures and sort of interrupting their day-to-day life. So that brings me to how often did people in the study get TPE? Um, I know this brings us into the different arms that were studied. So you mentioned that one study got immunoglobulin. Perhaps you can say a bit more about why that was and just unpick, you know, from the from the top, what were your study groups and how often were they getting these different treatments?

Brad Younggren 12:18

So we had three different treatment arms in the study. One arm patient got a treatment two times in a week, so just say like on a Tuesday and a Thursday. And they came back a month later later and got the same thing, and then a month later and got the same thing. So essentially six treatments over three months. And so that was one arm. Another arm did the same protocol that I just mentioned, but they also got a small dose of IVIG, IV immunoglobulin. Two grams. So what I would describe is generally much less than we would be targeting from a therapeutic perspective as clinicians in the hospital. So um, and there are a variety of reasons why that small dose was theorized as maybe to have some potential benefit. But the general idea of adding it was well, maybe there's some um protective um sort of immune protective uh factors that are being depleted temporarily, right, from the procedure. And so maybe you give back just a small dose of IVAG and that could be a benefit to the patient.

Brianna Stubbs 13:19

Tell us about um what aging clocks you used, um, what other measures. So you've mentioned proteomics already, um, and the main findings and how TPE affected biomarkers of aging.

Brad Younggren 13:31

The idea with the biological clocks, because that's the easiest to get through, probably the fastest, is uh there was no decision making about which clocks to use. We ran it all against the 36 clocks that seemed to be commercially available and uh for us to run it against at the time of the study. So that I think that was the best approach. Essentially means there was no bias about trying to pre-select the clocks you thought were better. I mean, there's a ton of opinion around this now. That way we just had all the data on all the different types of clocks that are out there, not one in particular. And we just aggregated that data across all the clocks to look at at an average biological age reduction as it related to the different cohorts.

Brianna Stubbs 14:08

As you've been getting into the space of um clocks and DNA methylation clocks specifically, um, what's your take on their overall utility? I mean, I think some of the research we're doing here is looking at even stability of the clocks, you know, within a day. And I think, you know, that they're obviously what's most most widely used in the field. And therefore, I this is a I think that the result is valid and interesting, but it's um I don't know, it's definitely an open question as to how um DNA methylation links to aging generally. So as someone, you know, I think you were in um digital health before you were with Circulate, I think, is that if that's right. Um so coming into aging a bit more and aging biology, what sort of struck you about our love of clocks, all things clocks and DNA methylation?

Brad Younggren 14:58

It's interesting. I mean, coming from AI, which is essentially where I was in my last job and healthcare AI, it's it's all it's quite different in a lot of ways. Um, my my simple approach to clocks is really, it seems like um the and I some of our advisors have sort of given me this sort of perspective that I have now over time, which is using clocks as a potential measure to a way to measure pre- and post-therapeutic uh intervention. So um I don't really ever talk about my clocks. I've certainly now in this job, almost two and a half years, like I've gotten plenty of clocks, but I don't ever talk about them publicly because I don't think it makes a lot of sense to sort of annotate what my biological clock is as it relates to my chronological age.

Brianna Stubbs 15:43

So what you're saying and the takeaway for you is that um not so necessarily useful for an individual, like how am I doing relative to my chronological age, but for you, um, running clinical trials pre and post-intervention, that that that a change there would be interesting and meaningful.

Brad Younggren 15:59

Right. And I think for patients too, or just people who are using them, if you're making a massive shift in some aspect of your habits or something, that that could be a really interesting thing to do. If you're if you drink heavily and you stop, yeah, check a clock in three to six months and see what the impact is.

Brianna Stubbs 16:15

I think that I think that's a great nugget for people to take away who are, you know, getting one of these done one time and either, you know, celebrating and never having it done again because they're 10 years younger or, you know, uh wringing their hands and wondering why they're 10 years older, and then also never getting it done again. So I think that's um a very helpful perspective. So um, you know, not to take away from like the the main uh message of the paper, what was the age reduction or what was the shift that you saw in the aging clocks pre and post-TPE intervention?

Brad Younggren 16:44

The average was 2.6 years in three months. So relatively impactful. I mean, if you if you compare what else is out in the industry, the various drugs interventions people are doing, um, and ask for human data about those, there's not a lot out there that really kind of compares to the data we found with plasma exchange, frankly. So um, from that perspective, we feel really strong where we sit in the in the therapeutic space here right now.

Brianna Stubbs 17:07

Yeah, we actually had another podcast guest on this series where we talked all about microplastics building up in the body and specifically in the brain. So I'm sure everyone who's listening to this episode will will be interested to hear whether or not TPE can reduce plasma microplastics. So we'll have to stay tuned for that by the sounds of things. So um you you saw this two and a half, two point two point six, is it, uh year reduction in aging over three months. Um what did you did you have any idea of the mechanism? You mentioned a couple of times reduction in inflammation. So can you say a bit more about that and perhaps um what the paper says about the the underlying drivers of that reduction in biological age?

Brad Younggren 17:46

I mean, that's a fair question. And again, it gets into the point how how do the scientific impacts of what we're seeing actually relate to the biological age reductions we're seeing? I think some of the other data we saw in the paper that uh you know was was highlighted by the authors uh around SAS proteins, lipoprotein reductions are also important components to to consider, sort of like things we would phenotypically expect to be upregulated, upregulated, excuse me, or downregulated as it relates to the omics is also likely probably more important in the long-term set of the data. So um, but I think obviously this notion of cellular rejuvenation or the impact of inflammation on aging is a cornerstone to the notion of this treatment being impactful. Um there's another component too that's interesting. It's not necessarily directly part of the paper, but but I think it's tangential and worth commenting on is now that we're in deep, and obviously we have more data than likely anyone uh as it relates to outpatient TP, and certainly as it relates to health span or longevity in plasma exchange, no one has our data set and um and or or the or as it relates to the exposome and the exposome impact on humans. So um in that sense, obviously we need to figure out exactly what uh what is in most impactful that's happening from an inflammation perspective. But obviously, like plasma exchange is a relatively, I describe it as a blood instrument because we're just taking out your plasma. So in general, we're able to like we don't have to fully understand, and I don't believe people fully understand the pathways. Obviously, if we did, we would be able to target, create a molecule that would magically solve aging. And of course, that we're nowhere near that right now. And so this approach sort of acknowledges the complexities of those pathways and acknowledges that um there's likely multiple factors that are important and um shows and demonstrates that much of that inflammation being removed sort of um in a timely fashion can have a significant impact on cellular rejuvenation, markers of aging, things of that nature.

Brianna Stubbs 19:50

So in the study you mentioned uh twice twice in a week and then monthly for three months. What um is your what's your ongoing um regimen for people who do this outside of clinical research? Is it something that would be monthly forever or um or different to that?

Brad Younggren 20:09

It's a great question. I mean, we came from the position where this was essentially we were bringing this uh out of the hospital. So understanding the sequence matters what the patient's primary medical problems are. So we service what we broadly call longevity in health span clinics, and then we have what we call chronic disease clinics. Those tend to be sicker patients with some heavy chronic diseases, um, taking care of patients with long COVID, MECFS syndrome, different things like that. So the protocol could be different based on the primary objective that the physician who's writing the prescription is interested in targeting. Um traditionally, patients have been coming in every four to six months to get a TP. But we're what we're evolving now to is trying to use biomarkers to understand and measure when actually someone needs to get plasma exchange. Now, I think for the scientists on this call or listening to this podcast, I'm sure you'd agree. I mean, like getting it to that level makes a lot of sense. Like, in other words, personalizing it based on biomarkers because we're all very different. And we have our patients come from very different backgrounds. Some smoke, some drink, many don't, and the longevity side. Some have certainly different genetic backgrounds that are going to predispose them. And the way I describe it to patients is, well, if we see you returning to whatever your baseline was, then that may be a really solid indication that coming back in for another plasma exchange makes good good sense.

Brianna Stubbs 21:33

So it is something that you'll you'll be doing on an ongoing basis to kind of click give everything a clean out, um, as it were, and maybe you'll be coming more often if you have less healthy lifestyle exposures that you don't otherwise address. Is there anyone um who shouldn't be doing it? I mean, is there the standard disclaimers around, you know, pregnant women and whatnot? They can't there's not very much they can do medically. Um, but any specific health conditions that are contraindications to TPE?

Brad Younggren 22:00

I mean, there are some relative contraindications, but interestingly, there's not a ton of absolute contraindications. We have physician and nursing leaders in the space working for circulate who can provide support and consultation to the clinics that we work with. And all this happens before the patient is even considered a candidate for plasma exchange. But interestingly, like patients who have anticoagulation, because many patients in this modern era are anticoagulated, it's not an absolute conduction. They may have to stop it for a few days, obviously, because you're about to stick a needle in them, but and take out a bunch of plasma, which also, when you do that, takes out additional clotting factors. So those are all considerations, but those are all things that could be considered for. So the most important foundation for me, similar to my last company in the primary care AI space, like start from a fundamental position of quality and safety, build your business around quality and safety, and the rest will follow.

Brianna Stubbs 22:52

It sounds like we're still in the stage where we're learning a lot about doing this outside of those specific disease populations. But it's excellent to hear that you're collecting all of that data and kind of leads me on to wonder is there a future where someone could self-administer this at home? Or is this always going to be, you know, require going to a clinic? You know, you worked previously in super scalable technology. So how do you think that this scales and becomes more accessible?

Brad Younggren 23:19

Yeah, I mean, there are mobile aphoresis units, like in big vans and trucks and things, but generally speaking, um, it requires a highly specialized nurse. We think there's probably only about 3,000 nurses in the United States who are properly trained on this machine. And properly, I mean people who have been trained in hospitals and have tons of experience. Those are the those are the people we hire. And so I think it will always be and likely should be in an outpatient clinic setting or in a mobile aphoresis unit setting. Um, not, I don't think it's ready for the home home setting world. I don't know if it ever will be, honestly. I there's so much to consider, and we want this to be really, really safe.

Brianna Stubbs 24:20

Um we talked about aging clocks as one readout as to whether it's successful, a successful longevity strategy. But and you did also mention some of my favorite, you know, tests like grip strength and up and go and things like that. Because I think um we're at an interesting point with the field where we don't, there's not a consensus around what is the biomarker, surrogate biomarker that tells you you're going to live longer or healthier, um, that isn't just watching you for 20 or 30 years and see if you actually do live longer and healthier. Um, and you know, there's a lot of discussion around um composites that include both function and biomarkers and bringing that together because really, as a as a patient, what we care about is if we can still walk to the store, get up and down the stairs, be socially engaged, things like that. So, um, how do you think about measuring success from a longevity standpoint of someone coming in and having this procedure?

Brad Younggren 25:14

Well, I think it's twofold. One of the interesting things when I started interviewing patients uh at the beginning of this journey was how many of them felt better after plasma exchange. So I had this aha moment where I was like, that's really interesting. It's not often we have therapies in medicine that make people feel better. Now, I'll be the first to say not everyone feels it. So we always sort of temper that expectation. But many people do. And um, so that's nice. Uh, because obviously if you have a sort of positive subjective reinforcement, it makes things easier. But what we really do is encourage and work with the clinics instead of programs to make sure biomarker testing is being done. And this doesn't have to be all the complicated, obviously, people aren't going to get massive proteomics testing every six months. Like that's not realistic. But there's even standard biomarkers that people measure that uh will be impacted by plasma exchange, as an example. Um, following homocysteine levels, um, looking at your LDL, looking at your HSCRP or CRP. These are things that you that are standard Quest lab that you can get, not complicated, and you can sort of follow along with therapy.

Brianna Stubbs 26:18

Yeah, so so really what you're saying, and the takeaway is this um this is helping uh move all of your biomarkers in a pro-longevity direction, just the standard, pretty much the standard things that you're gonna go and get measured at a lab anyway. So you don't necessarily need to do these additional fancy methylation or proteomics clocks to know that your blood work just generally is looking more healthy and youthful.

Brad Younggren 26:42

Yeah, yeah. I mean, it's tough. Like as an example with the circulate plastics trial, and we just presented the data at the first international microplastics conference in Santa Fe, and we're sort of submitting it for uh publication right now. But essentially we were able to show the plasma machines is really the only known therapy for reducing microplastics in the bloodstream. So um, you know, I can't get into all the details until we publish it, but um, and I think that's gonna be really exciting data to share. Most of us clinicians assume it's probably not a great idea to have these floating in your in your different organs. There was just something came out, I think, yesterday on um prostates that I saw microplastics and a higher level of microplastics, I think, in certain populations uh where the prostates were being um sort of dissected post-removal.

Brianna Stubbs 27:27

So it was interesting because in the discussion that I had with one of our previous guests about microplastics, they were saying that um we're just so exposed in our environment that there's not much that we can, you know. I asked if they did anything day to day to try and reduce their own accumulation of microplastics and not really was the answer. But it sounds like um TPE might be maybe then the only way of kind of getting, you know, it's not very, very many or any other ways to remove stuff that's building up inside the in the inside the body. So that if that's um real and true and we also can't make the policy changes that would reduce our exposure to plastics, um, then that could be a really exciting use case.

Brad Younggren 28:09

Yeah, it's very interesting. I mean, I've been knee deep in this topic for two years now, um, really passionate about it. And there it's a lot, we've learned a lot of interesting data. Like because we were testing people before they got plasma changed. So we're just testing what's their baseline level per se. That's based on habits. And you know, as you said, are they are they heating up plastic containers? There's so many things. But another one I think is probably really contextually relevant is where's the what's the water source of patients? Like um certain areas, like in the Pacific Northwest, um, interviewing patients. Like I drink the groundwater. I just drink tap water in Seattle, but it's glacier water, generally speaking. And my microplastics levels, as an example, were incredibly low.

Brianna Stubbs 28:50

Yeah. We were learning all about the way that it goes from the ocean and then it's used in, you know, to water crops and it's in the crops and it's in the livestock, and there's this sort of circle of recyc recirculating microplastics just sort of being passed around in the water in the food chain, unless you're getting it from like a really good pure source because it's not filtered.

Brad Younggren 29:11

Yeah, and then and then the clothes. That's the thing I didn't really personally know until I got into the research was the impact of our clothing and sort of the impact of like breathing in plastics. I'd like I thought it was all just like ingestion, but I, you know, I don't claim to be an expert, but that's why I have like Dr. Matt Campin on my advisory board to make sure I uh, you know, understand this industry as much as possible.

Brianna Stubbs 29:31

No, it's a super interesting potential application. And as you mentioned, I think we still still some work to be done before we understand what the uh we we assume negative impacts of buildup of microplastics would be, but that's not been it, it doesn't sound like that's been definitively established yet. But I mean, I think as you said, but that kind of thing building up in the body, I don't think anyone could imagine that that's a good thing. So I'm glad that you're um developing a uh solution, and that's it's it's it's really good to see. Um I want to pivot a little bit um looking at kind of like the menu of longevity strategies that there are out there. Um, obviously a lot of people talk about diet and exercise. That's a great place to start. Obviously, you know, there's nothing that's gonna replace making good lifestyle changes, but now we're starting to see more interest in various um drugs and gerotherapeutics, whether that is potentially GLP1s, although that's not been established and the classics like uh rapamycin or metformin. These are all working through, or the drugs, anyways, all seem to work through metabolic mechanisms. And what's interesting about TPE is it's working through this kind of completely different mechanism. So, how do you think about um how TPE might fit in with the menu of um prolongevity strategies, maybe in terms of how they might be combined, um, how their effects might compare in terms of magnitude and who might pick one rather than the other?

Brad Younggren 30:54

It's a great question. I think that without getting into some of the details of some of the projects we're involved with, I think that in the future it's gonna be a question of what do you couple with TP. So TP plus X, or because I think what we're finding is TP also is a really good uh way to sort of dampen the immune system. So the question is what are the sequence of events that you would like to occur to impact aging from a positive perspective or reduce the impact of aging? And so um as we explore these molecules and looking for synergy between what I think we're gonna find is that TP not only in and of itself is beneficial, but TP in combination with other agents may be even more beneficial. Um, and so that that's is really, I think, where the science will go the next five years. And I think we'll hopefully be at the center of it by just leveraging our affiliate network to look at some of these different um sort of modalities and um combination therapies, if you will.

Brianna Stubbs 31:54

Rome wasn't built in a day. We gotta lay up the evidence brick by brick and and then we'll see where it all falls out. So um I have a quote from you um that attaches a value to a healthy life of around 38 trillion US dollars. So um, can you tell me a bit more about where that number comes from and and how you think about the value of healthy life?

Brad Younggren 32:13

Yeah, thank you for that. I mean, I guess it all stems from the fundamental knowledge that chronic disease and chronic illness, which is taking a significant part of this population's as we age, we're not doing better with chronic disease, in fact, right? We're not we're doing worse. And not only is it um bad as a population, mitigates quality of life or health span, it's very expensive for you know countries to support the financial component of keeping people healthy and alive, right? And so if we lived healthier, the cost of um managing a population would go down. And so, and there's a lot of things we can do to help that become a reality. So um I think this notion of focusing on human health span. I mean, most people I've ever talked to are like if I'm gonna live to 100, I'm gonna live to like 99.9% of that with a high quality mobile, see my family, see my friends, and then kind of fall off the cliff, so to speak. So, like to that end, it's it's for me, I guess the the mission is less about life extension as it is for quality of life. I think that um I'm not I'm obviously excited about the notion of extending life as well. But I think the bigger problem being a physician um in in you know, my background is emergency medicine, by my remote background, it's like it we are sort of the we see the sickest of the sick and they're getting sicker, and it's like how do we help let people have higher quality of lives and help manage chronic disease? And part of that is really just preventive care.

Brianna Stubbs 33:46

The paradigm of of care in the US is definitely sick care and not health care, and trying to bring things more in line with early identification, uh being proactive and personalized about health. I think that all of us, um, you know, from our seat here in the longevity field, see that as probably the biggest lever that we can pull to um extend not just lifespan, but most importantly health span, those healthy, healthy years of life. And um I think getting getting more people aware of that concept is is a critical mission and um one that I'm glad that, you know, we're all participating in, all of us together. Is there anything that you haven't had a chance to talk about today that you wish someone gave you a chance to talk about that you'd want to sort of finish up with? Because I asked you a bunch of questions about the stuff I'm interested in, but is there anything that you're working on that um perhaps you want to share with the audience?

Brad Younggren 34:40

Thanks for asking. Yeah, I mean, I I'm I'm really, really interested right now um in the exposome and its impact on the human body. It's obviously doesn't live in a vacuum, like a lot of the chronic disease patients we're taking care of. Certainly there's impact and overlay into their chronic disease and autoimmune disorders, things of that nature. And we're seeing increases in these autoimmune disorders. We're identifying larger impacts of the exposome and the world we've created around us. So this is this is, I think, a really important component of preventive and/or of health span or preventive care that I probably underappreciated until I was really thinking about as deeply as I have been the last couple of years. Um, and you know, there's regulatory components to that. There's there's so many facets of that conversation, but I think it is a really important conversation that we need to have the next five years, which is how how are the how is the exposome and the environment around us impacting not only our daily lives, but the impact on chronic disease.

Brianna Stubbs 35:36

Have there been any things that you've changed in your own exposome as a result of your learnings in the last couple of years?

Brad Younggren 35:43

Well, I'm certainly was keen on my plastics numbers, but they were low, and I think it's I was already probably there for, and I don't, you know, one thing I've learned is regional matters, like probably water source matters, and obviously like uh the job you have matters. And this is one of the reasons we wanted to clarify this plastics work because we know there's professions that can't avoid high levels of exposure, right? It's just a nature of the job, and so having a potential option for them as a baseline use case is really compelling. Um, so I mean diet sleep and exercise, I was I was already there for the most part. You know, I'm an old army doc, so these things are drilled into us um back in the day. But so from that perspective, it's just uh continually working on sleep, I guess. And I you know, I'm not people always ask, I'm like, I'm not I'm not taking a bunch of peptides. This that's not me. I'm not saying me, not placing a value judgment on that either way, but I'm still waiting to see what's the right answer for me and um just continuing that exploration, I guess.

Brianna Stubbs 36:37

So, what's your top longevity sort of strategy that you do for yourself then? You mentioned sleep then. Is is sleep your number one that you go after?

Brad Younggren 36:44

I wish, I wish. I tell you, my my sleep's mostly back to normal, but during COVID, those were uh the more sleepless nights than I'd like to recall. But um, I think exercise for me is always just the fundamental core, just encourage and I always encourage people to start there because I mean, for me, it it's a great physical benefit, but for me, really what it is is it's it's my meditation. So it's my meditation, it's my private time. And I think that has such a positive mental impact on my ability to focus at work and you know have a have a great uh sort of awareness and presence with my family, things of that nature.

Brianna Stubbs 37:20

I completely agree with you. You're preaching to the choir. I'm an avid exerciser myself. Um and then uh one more, one more last question, seeing, seeing as they're not cutting me off just yet. But um when when you when you leave your professional field and you know kind of go off into retirement, I don't know whether you're one of those people who would never retire, but when when you look back at your career legacy, what's the you know, the top one or two things that you hope that you can look back and say that you've achieved across your career?

Brad Younggren 37:46

That's a great question. Um I love taking care of patients, and I that's why I still do. Um and but the whole reason um when I moved into technology, my earlier career I was in the Army, so I just got thrown in. I'd taken a scholarship for med school, and I got involved in technology procurement on the battlefield during like OIF and operation, you know, Iraq and Afghanistan conflicts. And I saw the impact of how technology was scaling to save lives, even back then in 2004. Um, that we didn't have nearly the technology development. My whole reason for moving in was that scalability notion. Like, okay, I wanted to go into medicine to try and impact people's lives, and this scales in a really different way. And that soon, second I stopped out of the army, I stepped into my first company. Um, this is my fifth one now. Um, and so I don't know what the right legacy is as far as the different technology I've helped support and build. But um I think many physicians, it's at the end of the day, it's just did we feel like we made people's lives better in the aggregate based on the work we did. Um, you know, we're still compelled to that notion of um doing good for patients. And I think this notion of bringing some science to helping support the longevity and health span field by bringing science and maybe bringing some new understanding and procedures and protocols is compelling. You know, a lot of our work truthfully it circulated around creating this affiliate clinic network that goes just beyond plasma exchange, is very powerful and allows clinics to collaborate in a non-competitive way to answer scientific questions and participate in ways that I don't think were achievable before we before we showed up. At least that's my hope.

Brianna Stubbs 39:27

We have discussed a lot of different um applications for TPE, all of which are really, really exciting. But why should someone, um, you know, just listening to this podcast, why do you think that they should be so excited about um TPE and specifically about what you're doing at Circulate to advance the research so that so that people can access it?

Brad Younggren 39:48

Oh my goodness. Like I said, I think we're entering the renaissance of plasma exchange, like something that has been stuck in the confines of a hospital for 20 some odd years, that we can start to look at what are the other roles that TPE can play in in human health span. And it goes beyond that. There's all this new exciting technology coming out with membrane filtration, so on and so forth. So I think like what we do for patients five years from now, even in the context of what Circulate does, will likely be different than it is today because we'll continue to gain insights and understandings of how to couple these things together or bring new technologies into the clinics, which are impacting not only longevity of patients, but their quality of lives.

Brianna Stubbs 40:27

This really sounds like something that we're all going to be seeing a lot more of as you do more of your research.

Brad Younggren 40:32

Yeah, I think so. I hope so.

Brianna Stubbs 40:34

That is a fantastic way to end our conversation. Thank you very much for your time and all of your wonderful insights um into this topic. And I I could talk to you for I could talk to you for another hour with all of my technical questions, but I'm afraid because we both have other things to do, we have to leave it there for today.

Brad Younggren 40:48

Thank you for having me on on the podcast.

Brianna Stubbs 40:52

Thank you so much for listening. Please subscribe, share, and give us a five-star review on Apple, Spotify, or wherever you get your podcasts.

Eric Verdin 40:59

We're not getting any younger yet is produced by Vital Mind Media. The Buck Institute's very own Robin Snyder is the executive producer. Wellington Bowler is right next to us here directing the recordings. And the esteemed Sharif Ezzat weaves the show together for you.

Brianna Stubbs 41:16

If you're listening to this podcast, you know that there has never been a more exciting time in research on aging. Discoveries in the labs are moving into the clinic to help us all live better longer. The Buck Institute depends on the support of people like you to carry on our breakthrough research. Please visit us at BuckInstitute.org to learn more and to donate.

Speaker 41:48

Investment advisory services are provided by Ashton Thomas Private Wealth LLC and Ashton Thomas Securities LLC, SEC Registered Investment Advisors. Securities are offered through Ashton Thomas Securities LLC, a registered broker dealer and member of FinROS CIPIC.