The Silent Fire Behind Chronic Disease—and How to Put It Out - Transcript

Dr. Mark Hyman
And what we know about that is that ninety five percent of chronic disease is caused by the exposome, not the genome. Meaning, your genes are are affected by the exposures that then change the gene's function, which then lead to all these diseases. But it's not the genes that are the problem, it's the exposome that's the major problem. Before we jump into today's episode, I want to share a few ways you can go deeper on your health journey.

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And if you prefer to listen without any breaks, don't forget you can enjoy every episode of this podcast ad free with Hyman Plus. Just open Apple Podcasts and tap try free to start your seven day free trial. Inflammation is a natural part of your body's function. It's essential. Yes, you cut yourself.

What happens? The white blood cells gather, they come to the site to rescue, they create swelling, they bring all kinds of healing factors, and what you see is redness and swelling and pain and heat. That is the classic sign of inflammation in the body. We used to call that medical score rubor dolor corlorn tumor. Tumor just means swelling, not tumor, know, it's anyway, Latin whatever.

But the key is that it's this normal process that happens as a result of dealing with problems that go wrong. But here's the rub. In the past, most of what we had to deal with was acute things that cause inflammation like a cut or an infection. But today, our modern lifestyle is driving so much hidden inflammation, systemic chronic inflammation, silent inflammation. It's a silent killer.

And it turns out that it's not the kind of inflammation that we are familiar with like a sprained ankle or a sore throat or something that's an obvious kind of inflammation, the kind that's good. The kind that we're talking about is the kind that's bad and that leads to almost every known disease of aging, heart disease, cancer, diabetes, Alzheimer's, not to mention things like ADD, depression, obviously autoimmune disease, obviously allergies, asthma, all sorts of gut issues. All these problems are caused by inflammation. Of course, then the question is, what causes inflammation? We're gonna get to that.

From a functional medicine perspective, I don't care that you're inflamed, I care about why you're inflamed. I don't want to give you an immune suppressant, an anti inflammatory drug, a pile of aspirin. I want to find out what the cause is and get rid of In functional medicine, there's a simple rule and it's this. It's called the TAC rule. If you're standing on a TAC, it takes a lot of aspirin to make it feel better.

Take out the TAC. And if you're standing on two TACs, taking one out doesn't make you 50% better. So get rid of both of them. Okay? And all of them.

Maybe there's five or 10 tacs. And that's the secret of functional medicine. It's a method of investigating the body as a system, looking for root causes and getting the body back in balance. Alright. So what is the deal with this inflammation?

I mean, I think, you know, when I when I was in medical school, heart disease was a plumbing problem. You know, it was clogged arteries. We now know that it's an inflammation problem. That the reason your cholesterol becomes an issue is because it gets inflamed and white blood cells stop up soup sop up the cholesterol and stick it in the arteries causing plaque. Same thing happens in the brain.

Alzheimer's is inflammation in the brain. All those plaques in the brain come from inflammation. So cancer also is a disease of inflammation. And when you forget to look at various studies, even with cholesterol, if your if your inflammation level is high but your cholesterol is also high, you're at high risk. But if your cholesterol is normal and your inflammation is normal, you're no risk.

But if your cholesterol is high and your inflammation is not high, you're really not great risk. And the worst is if you have obviously both. So inflammation is a real big issue. They did a study of an elderly population. They found that if their CRP was high, which is a blood test for inflammation, and interleukin six and other cytokine tests for inflammation, they had a two hundred and sixty percent more likely chance of dying in the next four years.

So this is no joke. So you might feel fine. Other patient, he's like, I don't know what's wrong. I feel fine. I don't I saw my blood test says, I don't really care.

I feel fine. Why should I change what I'm doing? I'm like, well, if you don't change what you're doing, it might not go well for you. Now there's no guarantees that's true, but it's it's likely true. So the real concern isn't our response to an injury or an acute infection or something like that but this chronic smoldering inflammation that slowly destroys our organs and our ability to function and leads to rapid aging.

In fact, I just finished my book on aging called Young Forever and they talk about the hallmarks of aging, one of the key hallmarks is inflammation, or they call it aging itself, inflammaging. And what happens with aging is there's this runaway inflammation that just degrades your whole body. So understanding what inflammation is, how to diagnose it and how to deal with it and get rid of it is so essential if you want to be healthy. Now, what's the problem with the treatments we use? Why not just take Advil or aspirin or take a steroid like prednisone?

Well, they're fine for acute problems but when things are in this slow smoldering state they really don't work. In fact, the new data on aspirin was pretty scary about heart disease. Oh, it's gonna help you and stabilize your blood and blah blah blah and prevent clotting, but it turns out that the recommendations for aspirin were over enthusiastic and that there are certain patients who should be on aspirin, but very few compared to the you know universal statement that everybody should take an aspirin to prevent heart disease. No, because it causes strokes and it causes bleeding which is not good like GI bleeding. So you know, if you look at those drugs like aspirin or Advil or Aleve, they're not benign.

Mean, they're really helpful when you need them, but they can cause terrible gut issues. I had gastritis, for example, after taking them for a broken arm, and many, many people die. In fact, many as many people die from taking those drugs as from asthma or leukemia. So imagine if we literally eliminate those drugs, we'd basically be essential. It'd be the equivalent of curing leukemia or asthma.

So it's not not a joke. So, you know, statins, for example, even cholesterol drugs like statins like Lipitor, they may not have their main effect by lowering cholesterol. In fact, it may be because they actually lower inflammation. That's what they do. It's a side, quote a side effect of the statin but actually may be their main effect.

So how do you know if you have inflammation? Is there a way to test for it? Is there a blood test? Well there are and there are more and more coming. So the most common one that people do is called C reactive protein.

It's high sensitivity C reactive protein. It's something your doctor can order. It's on any lab panel you can get. And you can also see that as a sign of hidden inflammation. Now if it's super high it could be infection, but if it's in the sort of one to 10 range that's usually the hidden inflammation.

There there ideally it should be less than one, any higher than that means you're on your way. Now there are other blood tests you can check, cytokines, sed rate and so forth, may not be as helpful. But there's a new test by, developed by a professor at Stanford called I Age, I A G E, meaning immune age, and it really looks at your, immuno, which are 50 different cytokines, many of which you've never heard of, they're molecules that are regulating immunity inflammation, that he was able to correlate by using artificial intelligence with disease. So he found there really there were about four that highly correlated with your risk of heart attack, cancer, diabetes, Alzheimer's and so What's so amazing is this test is really not that expensive. It's easy to get and you can track it over time.

And then the good news is you can change things and change your inflammation. Anyway, enough with that. So, you know, the reason we really don't track this is because doctors just kinda are not thinking about the root causes of disease. They're like, okay, what's your symptom? What are you suffering from?

Okay, let me find the drug that best matches that. You know, if you have a strep throat and can give you penicillin, great, I'll get a cure. But most of time, I'm just managing symptoms and or I'm giving you an immune suppressant. And that's not the answer, unfortunately. So Okay, so let's say you've identified the causes, you figured out you have inflammation.

You know, how do you live an anti inflammatory lifestyle? It's the same old stuff. Hate to say it, but it's eat real food, lots of phytochemicals, all those colorful plant compounds are anti inflammatory. All the the phytochemicals in food are so powerful for reducing inflammation. Also, you know, just real whole unrefined unprocessed foods, not lots of sugar and starch, no trans fats, no refined oils and get lots of those phytonutrients.

Good fats are really important too. Avocados, olive oil, extra virgin olive oil ideally, omega three fats, things like sardines, herring, sable, wild salmon, they're all really rich in omega three fats and they're very healthy for you. Exercise. Lots of research on exercise can reduce inflammation, it supports your immune system, it strengthens your heart, it corrects insulin resistance and improves your mood, it helps reduce stress. I mean it's one of those miracle therapies that can really do so much for you at so many levels.

Practice active relaxation, which sounds like a contradiction or an oxymoron, but no, you have to actively relax. It's not I don't mean sitting watching TV drinking a beer. I mean meditating, doing yoga, deep breathing, getting a massage, doing something where your body just kinda hits down into the parasympathetic state and calms your nervous system. Hot bath, I love that. Last night I was little had a very busy day, lots going on, and I just took a hot bath with Epsom salt and I just kinda floated away, it was great.

Also food sensitivities are another big factor. You might not know this but a lot of hidden inflammation can come from not allergies but food sensitivities, things like gluten, dairy and certain things that people react to that they may not know they react to. So I often recommend an elimination diet, like the ten day detox diet that I've created to help people reduce their overall level of inflammation and then you can add back foods and see what's really the problem. So maybe I eliminate a lot of things and then you just add back one at a time and, for example, dairy I know causes inflammation. If I have dairy, I get pimples, my skin's weird, I get congestion, so I don't eat dairy.

Although I do manage to tolerate goat and sheep okay. Many people would benefit from actually a focused gut repair program because a lot of their imbalanced bacteria are causing inflammation. And lastly, take the right supplements. A multivitamin, fish oil, vitamin D all help drop inflammation.

Dr. Shilpa Ravella
We know today that exercise actually can dampen inflammation in the body. We have dozens of clinical trials to back this up. And even in the absence of weight loss, the exercise can decrease the amount of immune cells that are infiltrating your fat tissue. To me, that's an amazing fact because we're not just looking at the end result, weight loss. We're actually changing our bodies on a biological level, even if we are not able to see it on the outside.

Just getting out and moving every day, even if you do it in small bursts, that tends to add up. For example, if you take your bike instead of the train, or if you try to go up the stairs instead of taking the elevator. All of these different things can actually add some exercise in your day, some movement in your day. When you think about the Blue Zones folks, this is how they incorporated some movement into their days. I think it's a very seamless way to do it.

Nothing wrong with going to the gym and exercising or anything like that. But for most people, it's this difficult thing to begin exercising when they have not done any of it, especially some of my patients who come to me saying, Doc, I don't have time to incorporate exercise into my day. This is something I think that anyone can do just by making some simple lifestyle changes and it can actually dampen the inflammation in the body. Another thing too, I think, is to just be mindful of the times at which you're eating, because fasting has been shown to dampen inflammation in the body, to fortify your body against a variety of diseases. Just something as simple as trying to consume your calories in a ten hour window.

It doesn't have to be anything complicated. Of course, if you have comorbidities, then you should speak to your physician and a nutritionist before attempting a fasting program. But we do know that stressors like exercise and fasting are good stress in our life because we have to have the good stress and also maintain the bad stress that we don't want. Those things I think are very important for inflammation.

Dr. Mark Hyman
Yeah, I think that's really important to think about. I think exercise is so key. I think we, we, we, you know, we, we don't realize how powerful it is as a, as a trigger for all the beneficial things we want to have happen with aging. It works for depression, it works for heart disease, for cancer, for diabetes, for Alzheimer's, for every kind of inflammatory disease is pretty amazing. And yet, less than eight percent of Americans get the recommended exercise.

Right.

Dr. Shilpa Ravella
Maybe 20

Dr. Mark Hyman
if you take a broader view of what's minimal, but I think most people don't even get close to that. I think, what about the role of supplements or phytochemicals or other things that we can be taking to help regulate our immune system? Do you have any perspective on that?

Dr. Shilpa Ravella
I mean, I do love to tell patients to get their phytochemicals from the foods first. I basically, I have my patients eat lots and lots of colorful vegetables. We know that polyphenols are incredibly important phytochemicals for inflammation. They're antioxidants. They help to tone inflammation down in the body.

They are also metabolized by the gut microbiome in part and more beneficial compounds are created. I certainly think that polyphenols have a major role. When I think about supplements, I think it's more the exception than the rule. When you look at supplements like curcumin supplements, some of which have been shown to be efficacious in diseases like inflammatory bowel disease, that's a great thing. You can also use curcumin in your cooking, for example.

I think with supplements, as long as you have the data behind them, then that could be something that is potentially beneficial depending on your disease process as well.

Dr. Mark Hyman
The things that I tend to recommend people to eat are certain foods which have anti inflammatory compounds. What are your top anti inflammatory foods that people should be focused on?

Dr. Shilpa Ravella
Well, I really love grains. I think kale is one of my favorite grains. It has the immune modulating potential of our ancestors, our ancestral plants. It's very versatile, very easy to cook. We want to try to get to foods that are more like those ancestral plants, like scallions instead of onions, for example, because the ancestral iterations are actually much more powerful from an inflammation damping standpoint.

Berries, again, are a wonderful food. You can have frozen berries, for example, just in your freezer and eat them whenever you want. They're filled with variety of phytochemicals, including polyphenols. When you think about inflammation, you really want to think about the very, very colorful foods, not just the iceberg lettuce and the bananas. In my pantry, I have a variety of whole grains and by whole grains, I mean actually whole.

I love quinoa, it's one of my favorite grains. I think it's something that is very easy to use. Whole intact grains are actually much better for your gut microbiome than processed grains. So that's just something that's a nuance that can be helpful when it comes to talking about inflammation. Also fermentation.

Of those grains. So I think that when we are talking about grains in general or certain foods, we really do need to be looking at the nuances. That you have a hearty bread that's fermented and baked in the ancient tradition without any flour, that's a very different response in terms of your immune response than a bread that you buy at the supermarket. That's something to be very mindful of. I love beans as well and lentils.

There are dozens of randomized controlled trials showing that beans can help to dampen inflammation and beans have a good amount of soluble fiber. You probably know all of this already, so I'm just regurgitating what you already Oh, know yeah.

Dr. Mark Hyman
It's great. People need to hear it. People need

Dr. Shilpa Ravella
But that's It's probably the

Dr. Mark Hyman
everybody listening.

Dr. Shilpa Ravella
Yeah. So the soluble fiber is very important for the gut germs. They metabolize that fiber and salvage calories that way. You make beneficial compounds that go throughout the body and calm the immune system down. And one thing I think that-

Dr. Mark Hyman
So feeding you, I'm just, I don't want you to skip over that. Feeding your microbiome is so important, right?

Dr. Shilpa Ravella
It's incredibly important.

Dr. Mark Hyman
And also those polyphenols, which is really a thing to discovery. Yep. So they they're not using fiber, but they're eating all the colorful plant compounds that can improve their their bacterial content in there.

Dr. Shilpa Ravella
And they're also eating some fat, like healthy fats from nuts and seeds. That's another food that I prescribe for patients. All those healthy monounsaturated fats and just a handful of nuts a day is a great thing to add into the diet. Then something I think that people tend to forget about are just spices and herbs. I mean, are so many different spices you can use.

In my family's traditions, the cuisines that my parents and grandparents cook, they're just an array of spices that I can't even I still have to learn all the names of everything. Spices and herbs are just filled with polyphenols and just very, very beneficial nutrients. If you look at something like cumin, which has salicylic acid in it, you're actually getting some anti inflammatory potential from that, which also helps to resolve inflammation. Because aspirin is one of the few medications that actually not only dampens, but also resolves inflammation. Just thinking of things A

Dr. Mark Hyman
lot you were talking during COVID about using black cumin seed oil. Black cumin seeds are a really different kind of cumin, and it's a very powerful immune modulator and anti inflammatory, potentially antiviral. Yeah. So these these spices are we we sort of neglect. You know, we use a lot of salt, a lot of sugar, a lot of processed refined oils to kind of make food taste good.

And we don't actually use the spices. And then you don't really need that much of those other things when you actually have a yummy, spicy, yummy diet. I mean, I I love to cook Indian food at home. I actually make it scratch stuff. So, like, I actually get the actual spices.

I grind them. I get the. Oh, that's wonderful. Yeah. And it's like, oh, it's so good.

It's like an and

Dr. Shilpa Ravella
it's a lot of hard work. It's a lot of hard work. Well, I have I have a little, you

Dr. Mark Hyman
know, I have a little, like, a brawn like thing. It's just like I just push the button and go. So it's like this fires. But it's it's it's so important to start include these in your diet on a regular basis.

Dr. Shilpa Ravella
Absolutely. The one thing I want to mention, the last thing is also seaweed, because I love seaweed and it's kind of like a super food in some ways. You can find fibers in seaweed that you don't find in terrestrial plants.

Dr. Mark Hyman
Yeah. Tell us about that.

Dr. Shilpa Ravella
The goal is just to have a diverse array of sugar based plants. We know that simply by increasing the diversity of plant foods in the diet, that can actually predict lower inflammation. It's not just about the quantity, but also the diversity. Just kind of thinking about all of these different types of foods that you can get, I think, could be pretty useful.

Dr. David Furman
I've been studying social and exposome determinants of inflammation for about fifteen years now. Type of data that is out there point very clearly to things that most of us know. However, there are certain aspects of the exposome that that we do not know are

Dr. Mark Hyman
What's the exposome? Like, what's what's in

Dr. David Furman
Exposome? Yeah. Yeah. Yeah. So it's the totality of biological, chemical, and social exposures that a person suffers throughout their life course.

Dr. Mark Hyman
Mhmm. And what we know about that is that ninety five percent of chronic disease is caused by the exposome, not the genome. Meaning, your genes are are affected by the exposures that then change the gene's function, which then lead to all these diseases. But it's not the genes that that are the problem. It's the exposome that's the major problem for most of us.

Dr. David Furman
That's exactly right. I I would like to get at that in a moment. We have the genome, everybody, you and I and everybody in this this world, to be able to live a hundred and twenty, a hundred and thirty years, at least. Right? That is something we know.

Now, the problem is in some countries, people are dying at the age of 70, 75. That's the average lifespan expectancy. Some countries it's 89 or 90, like Monaco or Japan, because we figure out ways to extend that period of healthy living. So in essence, what we're trying to achieve is to push that eighty to ninety average life expectancy to 120. Now, tweaking genes is a completely different thing.

We're not going to talk about that at this podcast. But I'd like to go to idea of the exposome. Yeah. Back to the root cause of inflammation. So we do know already today that pollutants in the air, that pollutants in water.

Pollution. Pollution, exactly. Pollution are drivers of inflammation. Imbalances in nutrition, such as both macro and micronutrients, right? These cause inflammation by large.

Food additives go back to the microbiome, things like carboxymethylcellulose or polysorbate 80 that will wipe out your microbiome and will cause inflammation because the mucin layer in your linen of your gut will get very thin. And then you're going to have translocation of different antigens to your periphery, and you're gonna develop an inflammatory reaction. Gluten, you know, gliadin, it's

Dr. Mark Hyman
a I'm I can use gonna hold on. What you said was very important. You you just said that basically when you eat these food additives, things that are in our food that we don't even pay attention to, polysorbate 80, It damages your gut lining. And then all the poop and bad like, in food particles that are partially digested leak across that, and your immune system is right under the lining of your gut. And then your immune system goes, hey.

What's this bad foreign stuff? And it starts creating this inflammation. So that's why it's bad. So food additives are just not bad because they're you know, if you're a hippie and you wanna eat granola and, like, this, you shouldn't eat food additives. They're really damaging to our bodies.

Right?

Dr. David Furman
Your microbiome. Yeah. Exactly. They're they're causing this concept of dysbiosis, right, in your gut.

Dr. Mark Hyman
You were going gluten was the next thing you were going into.

Dr. David Furman
Exactly. So or or plasticizers. Plastics, things that are are stored in plasticizers or plasticizers and plus the resin make a plastic and there's leaching, right? And there's a leaching of plasticizers that go into our foods. And those are hormone disruptors that also cause inflammation long term.

I was going to go to gluten. Gluten, as you know, is highly inflammatory. Gliadin can bind to certain cells in your gut and cause inflammation, increasing leaky gut, etcetera. The other one is sedentarism. As you very well are aware, if we're sitting in a chair, we're developing an inflammatory reaction that it's

Dr. Mark Hyman
a very I'm

Dr. David Furman
a clean going detention. Time sitting in a chair and mortality, there's almost a perfect correlation between those two. Sleep quality, disruption in our circadian rhythm, social stress. There's a very, very compelling evidence that individuals that are exposed chronically to social stress, social isolation, they develop inflammation, they have more cardiovascular disease, elevated rates and death. And obviously, other chemicals that we're exposed to that are surrounding us, just even a good example, formaldehyde.

Right? Paraformaldehyde that serves as a glue for plywood that is often used in furniture and cabinetry.

Dr. Mark Hyman
So those are important things. So basically, it's environmental toxins, it's social stresses, it's inflammatory foods like sugar, it's food additives and, and even other environmental toxins didn't even mention like heavy metals, not just plastics. We're exposed to all this stuff and that and our gut microbiome becomes disturbed because of a lot of these things, and that even creates worse inflammation. So we're in this inflammatory environment, which historically we really didn't have, throughout evolution. And the truth is we did a lot of things that naturally combated inflammation.

So just as there's an inflammatory lifestyle, there's an anti inflammatory lifestyle. Right? And so the beauty of your work, and I want to get into this in a minute, is that you've been able to map out the changes in the immuno. And for those who don't know what that is, it's basically the sort of immune well, why don't you define the immuno? You're the expert.

Probably I screw it up. But it

Dr. David Furman
I I doubt I doubt you you will. But so similar to the concept of exposome, the the the the end and the word SOM accounts for the totality of it. So when we talk about the immunome, talk about all the cells, the proteins and the genes that are in your immune system that are able to communicate between them. Right? And so orchestrate an immune response.

So we're talking about hundreds of thousands of different parameters that can be measured from blood. That's what we did in 1,000 Immunomes Project, which is a project that, as you mentioned, lasted for about now fifteen years. We just got another source of funding from NIH, 15,000,000 to continue the study Amazing. For the next five And we've been monitoring these individuals, their immunome. And basically we focus it in blood.

We take cells, genes, proteins in the blood. And as you mentioned before, the biomarkers that are currently existing for what we believe is inflammation such as CRP, HSCRP, sedimentation rate, that you can go to the doctor and have those, are very poor predictors of any type of condition. CRP, just to give an example, is predictive of cardiovascular events with a power of 0.6. The area under the curve when you're trying to predict cardiovascular events is almost close to random chance. Right?

Studies- So

Dr. Mark Hyman
how cold is not very sensitive. It's not very sensitive.

Dr. David Furman
It's not very sensitive as a measure for systemic chronic inflammation. Exactly. And that's where this whole idea of discovering new biomarkers, but looking at the immune system in an unbiased fashion comes into play. And that's what we did. So what we are what we are using is not only technology that help us measure all these things, but also computational analytical tools that are rather novel, including AIML, right, machine learning, to be able to cope with the data and to derive metrics that are simplified, that that take us hundreds of thousands of hours.

Now we have a metric that can be used in the clinic. Right? So it's like finding a needle

Dr. Mark Hyman
in the haystack, and it's a way of doing that, which is very hard to do in medicine.

Dr. David Furman
Right? That's exactly right. That's exactly right. But the medicine and the clinical medicine are also research is changing. So there's now a lot of different groups across the world.

Here in The US, it's very popular to do transcriptomics, proteomics, and we're measuring 7,000 proteins in the blood, 3,500 metabolites. And it it becomes much more normal. Has you know, it has normalized with time. Yeah.

Dr. Mark Hyman
So when you did the thousand immunomes project, were you measuring, you know, how many analytes? Because I remember reading the paper and there were like 50 cytokines that you looked at. But but was there a lot of other stuff you also measured besides those 50?

Dr. David Furman
Right. So we measure the expression of genes, and these are roughly 15,000 genes that we measure from a drop of blood, basically. Also measure cells that are circulating in the body, and these are immunological cells, around 25 different cell types. And we also measure metabolites. And the 50 proteins that we measured across these different years, this is a panel that was expanded now.

We're currently measuring 7,000 proteins from individuals. Making sense of that is challenge here. It's really a beautiful system that this company has started, I would say, maybe ten years ago or so, in which they can now analyze 7,000 proteins. There are other companies analyzing 35 or 4,000 proteins, and we're measuring all these things to see how those contribute to rates of aging.

Dr. Mark Hyman
So in a way, this is something that's never been possible before because you have this convergence of the framework of systems biology, understanding the body's a network where there's this dynamic interactions of thousands and thousands and maybe trillions of chemical reactions every minute, And you can measure through advanced technologies, thousands and thousands of proteins, the expression of thousands of genes, the analytics that help you process that data, which is so hard with bioinformatics and, you know, computational tools like AI and machine learning, which really didn't exist before. And so as a doctor, I'm so excited because it's always been really clear to me that we're missing stuff that we, you know, we, you know, we we do an exam and we do lab tests pretty much like we've been doing for the last hundred years without a change. Exactly. You know, it's like, come on, guys. There's like more going on here.

And we get stuck in the way we do things. But you're kind of blowing the lid off it. And and what you did was was then correlate things that would be hard for the average, you know, scientist in this lab, like, you know, with graphs and maps and things to figure out, correlate which of these analytes and proteins and cytokines and biomarkers were correlated with different diseases and the rate of aging. So sort of sort of explain what you found as you begin to sort of unpack the extraordinary amount of data and what were the kind of nuggets that you came up with in terms of identifying the things that we should be looking at? And there are honestly things I never even heard of as a doctor that I don't even remember.

They maybe they taught me medical school, but I don't even think we knew about it then. So it's like it's so exciting of like, oh, there's this cool thing that that is so different that I never even heard about, that that may be actually more more relevant than anything else I've figured out, like, you know, CXCL nine, which is a chemokine. Well, I never heard of that, but that may be more important than anything else we're measuring on our blood work. Right?

Dr. David Furman
Yeah. So that's a great segue for what I wanted to discuss with regards to how this inflammatory age metric that we build is predictive of diseases. We can predict the age of individuals by just a selfie. That's easy.

Dr. Mark Hyman
Can do a selfie of me. Old do I look?

Dr. David Furman
You can also take any blood biomarker, predict the age. Age prediction of age is easy because things change with age. That's not the complicated part. The interesting part is once you take these immune biomarkers and try to predict the age of individuals, so you, in essence, are you generating a clock, a biological clock, a new clock of aging. And this is an inflammatory clock because we're looking at the immune system and inflammation as our source of data.

So we build that inflammatory clock that is able to accurately predict the age of an individual. Nothing very fancy. Now when we adjust for age, that means that for a given age group, we see those that are deviated upwards versus those that are protected, deviated downwards. So in other words, they have an inflammatory age that is beneficial according to their age. Then we find that those that with higher inflammatory age according to their age, are at risk for developing multimorbidity.

That's the first finding.

Dr. Mark Hyman
Multimorbidity is what?

Dr. David Furman
Multimorbidity is defined as the sum of multiple diseases, in this case, non communicable diseases of aging. So say someone could have a musculoskeletal condition, that's one disease. If that person also suffers from cardiovascular conditions or some events in the cardiovascular system, that's two diseases. And then you add up to 10 diseases. And this is very common, as you know well, in The US and also in other parts of the world.

After the age of 65, we're suffering from around eight to 10 diseases, and we're taking about 14 to 15 different medications. So it's huge, it's huge. So what we're trying to here identify is a biomarker from blood that is focusing the immune system that is able to predict multiple diseases simultaneously. So this is multi morbidity, that concept. And then we went ahead and did a whole slew of different studies.

We looked at frailty in individuals. So frailty is measured by asking individuals whether or not they're independent enough and you take the grip strength and the time up and go, functional measurements in individuals. And we're able to predict with the inflammatory age, seven years before it happens, who's going to become fat. Wow. So that's another big discovery that we did that we published last year in Nature Aging.

And also CXCL9, as you just mentioned, one of the most important contributors of inflammatory age of this new metric is a chemokine that is part of the immune system proteins in the blood that has not been identified before as a marker of systemic chronic inflammation. Right? And markers that are usually coming up in the inflammatory reaction against pathogens, that's easy to measure. Interleukin-six, TNF alpha, interleukin-one beta, those are well established canonical markers for acute inflammation.

Dr. Mark Hyman
Those are cytokines, like we talked about with the cytokines formed with COVID. So those are yeah. Those are the typical cytokines. Right?

Dr. David Furman
Exactly. And those allow for cell to cell communication. In this case, we're talking about a very different set of proteins that are coming up as being the most predictive. And then we went ahead and looked at a number of different cardiovascular phenotyping measurements in these individuals, and we're able to correlate CXCL9 with cardiovascular aging, with cardiovascular health. And then we went ahead and continued this study to look for mechanisms and to explain other morbidities, we published that last year in 2021.

Dr. Mark Hyman
So basically, eye age biomarkers and as I understand, there's a smaller panel and expanded panel. So out of these thousands and thousands of things, you found like four key ones that you can measure now on a blood test. And and there's others that are an expanded one. Maybe it's seven or eight. I don't remember the number, but there there's not an infinite number of these.

And and in those kind of biomarkers, you're able to identify the rate of aging and also the risk of chronic diseases. And whether it's dementia or heart disease or cancer or diabetes, these are all inflammatory diseases. Right? Correct.

Dr. David Furman
So the understanding of these diseases is very poor, as we know. Otherwise, we wouldn't suffer from those. And so only as I mentioned at the beginning of this conversation, twenty years ago, we started looking at the immune system as a major root cause of these diseases. And we are just starting to derive the biomarkers. This is rather new, right?

And you're absolutely right. From looking at this extended panel of cytokines and proteins in the blood, we identify key five. It's a core five biomarkers, including this one, CXCL9, that is, by the way, largely produced by your endothelium. So it's not just immune cells What's The endothelium is the cells that are making up your vessels. Right?

Dr. Mark Hyman
They're lining your blood vessels.

Dr. David Furman
Exactly. Your blood vessels, lining up

Dr. Mark Hyman
And your blood

Dr. David Furman
those cells can become inflammatory. So as you get older and we treat our bodies in different ways, those cells become senescence and they start producing CXCL9, and then you have all these downstream effects that we just mentioned a few minutes

Dr. Mark Hyman
And so what are these these these cytokines and chemokines? What what are they doing? Like, how are they accelerating aging? And are they the cause of heart disease? Are they the cause of dementia?

You know, are they just correlated with them?

Dr. David Furman
That's a very that's a great question. It's a little bit of a loaded question. Mhmm. And and I'm saying that because we would need a lot of mechanistic studies to demonstrate the relationship between every one of these proteins and the causal inference in tissues and degradation of organs. We did that for a single one, right?

CXCL9. When we take CXCL9 and incubate, that means that we put in a petri dish and we start growing cells in the presence of CXCL9, these endothelial cells are completely dysfunctional. They don't respond well to acetylcholine. They don't contract. They don't have the production of tubes that you need.

So these are completely dysfunctional endothelial cells. And then we also see that cardiomyocytes, which are the cells that are in our heart, are suffering from the presence of CXCL9 in the body. So when we now block, let's say block, right, we block CXCL9 by introducing what we call silencing of the protein. In this case, we use an SHRNA. We can restore completely that the function of those cells.

Dr. Mark Hyman
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