Inflammation, Aging, & How to Put Out the Fires Your Body Keeps Setting | with David Furman, PhD

0:00Jonathan Fields: So every year, someone in a white coat probably draws your blood, circles a number, and tells you that's your inflammation level. Turns out that number may be barely more accurate than a coin flip. And the real story of what's aging you from the inside out, it's almost nothing like what's on that lab report. In today's conversation, you'll discover why everyday objects in our house, probably sitting right in your living room right now, might be quietly raising one of the biological markers tied to heart disease and aging. Why chronic stress can make anti-inflammatory drugs stop working, no matter how much you take.

0:34Jonathan Fields: We'll talk about the single 10-minute habit that our guest says can add about 15 years to how long you stay healthy. The changes in lifestyle that make the biggest difference. We'll talk about what GLP-1s might actually be doing to slow aging that has nothing to do with weight loss. We'll also explore why a food fight everyone's already having, gluten in or out, It might have a real biological mechanism behind it that accelerates aging and inflammation. And we'll discover the small kind of unglamorous morning ritual that our guest credits with keeping his own inflammation down and the groundbreaking new tests that can now predict who's headed towards frailty seven years before it happens.

1:13Jonathan Fields: Our guide is Stanford immunologist David Furman, the director of the Stanford 1000 Immunones Project and the Bioinformatics and Data Science Corps at the Buck Institute for Research on Aging. So excited to share this conversation with you. I'm Jonathan Fields, and this is Good Life Project. And we'll jump in right after this short break.

1:37Jonathan Fields: Good Life Project is sponsored by Talk Dietry. So here's something that comes up a lot in midlife. You've done the inner work, maybe years of therapy, and there's still a weight that won't lift. Is it just a rough patch or maybe something more? That's where psychiatry can help. Talkiatry is a 100 % online psychiatry practice offering comprehensive evaluations, diagnoses, and ongoing medication management for conditions like ADHD, anxiety, depression, and more. And finding a psychiatrist who takes your insurance, all 800 plus talkiatry clinicians are in network with major insurers. Take a short online assessment, get matched, and see someone in days, not months.

2:16Jonathan Fields: You stay with the same provider so your care evolves with you. Over 300 ,000 patients have found care this way. Head to talkiatry.com slash goodlife to complete the short assessment and get matched with an in-network psychiatrist in just a few minutes. That's T-A-L-K-I-A-T-R-Y dot com slash goodlife to get matched in minutes. Talkiatry.com slash goodlife. Good Life Project is supported by Peloton. So full honesty here, I am not a runner. Never really have been. I'm a hiker. Give me a trail, some elevation, and a few hours, and I am genuinely happy. But here's the thing about the Peloton Tread Flex that really got my attention.

2:55Jonathan Fields: It's not really pitched at runners so much as it is at people who just want to move, you know, walk, hike in place, or let a walk turn into a jog if the day feels right. No pressure to perform, just movement on your terms. And incredibly convenient, no matter what life or the weather brings you. The new Peloton Treadflex is built for this. It's foldable and movable. It fits into an actual home, not the home gym that most people don't actually have. Everybody's got a corner. Just roll it out, walk, hike, jog if you're feeling it, and then roll it right back where it came from. And once you're on it, you've got instructors who feel more like friends than drill sergeants with programs for wherever you're starting from call yourself a runner if you're just getting into it all the way to full race training if that's your world.

3:39Jonathan Fields: Let yourself run. Explore the new Peloton Tread Flex at OnePeloton.com. This episode is brought to you by Choiceology, an original podcast from Charles Schwab, hosted by Katie Milkman, an award-winning behavioral scientist and author of the bestselling book, How to Change. Choiceology is a show about the psychology and economics behind our decisions. Hear true stories from Nobel laureates, authors, athletes, and everyday people about why we do the things we do. Listen to Choiceology at schwab.com slash podcast or wherever you listen. So we've all heard the word inflammation. If you're paying any attention to health, to well-being, to aging these days, the word inflammation just keeps popping up in the conversation, in the news, in the media, in individual conversations.

4:28Jonathan Fields: Probably if you've gone to a healthcare practitioner, you've heard that word, especially if you're in your 40s, 50s, 60s. And often it is attached to a wide range of conditions. You're somebody who has studied inflammation, chronic inflammation, especially as we age, and also seen its relationship to a wide variety of diseases, heart disease, diabetes, dementia, cancer. These are all outwardly different conditions. How does inflammation tie them together? The clinical manifestations of these diseases are different. So these are indeed different conditions that are driven, at least in part, by a common denominator, a root cause, that we've been studying for now two decades, and that is systemic chronic age-related inflammation that increases as we age in some people more or less, and that's a determinant of most of these diseases.

5:28Jonathan Fields: So systemic chronic age-related inflammation, how is this different from the type of inflammation that we probably heard about when we were younger? You stub a toe, you sprain your ankle, you break a bone, or maybe you have a bad virus and we see some sort of inflammatory response in the body. Distinguish between that and the type of age-related chronic inflammation that you're talking about. They are very different entities. The acute form of inflammation is a response to your immune system, to viral infections, to bacterial infections, to other sorts of pathogens or trauma. If you cut your finger and it gets red and swollen and warm, those are signs of acute inflammation.

6:19And we can measure the different proteins that are secreted by immune cells. that is there are well-established biomarkers of acute inflammation. It's typically of high grade. So what that means is that these proteins go and are expressed in high quantities, but then they should go back down to a baseline. And that takes around three to seven days to clear up the infection or repair the tissue. In the case of age-related chronic inflammation, the sensors are different. So the receptors in the immune cells are completely different. This doesn't happen from one day to the other. It accumulates with age and is responsive to how we treat our bodies, our lifestyle decisions, our level of stress, the amount of plastics and plasticizers that we're exposed to and stuff like that.

7:18So very different monsters. And in case of acute inflammation. Again, they're well-established biomarkers. In the case of chronic inflammation,

7:27Jonathan Fields: there's not. So why is the inflammation that goes to heal something and lasts for three to seven days good, but the inflammation that accumulates in our body chronically over time and just kind of stays bad? Well, the immune system has evolved to protect us from infectious disease, protect us from injury. When we have a cut or we have any trauma, the immune system will repair that trauma. It's beneficial. And that's the purpose of the immune system as a sensory system. I usually like to call the immune system our sixth sense. So you're sensing the environment, you're reacting to it, and you're mobilizing immune cells.

8:19And the immune cells get activated, and they produce a number of different proteins that ultimately repair the tissue. And that's beneficial. In the case of chronic inflammation that's driven by your exposures and by aging, It's very detrimental. You're, I like to call it, you're fighting the ghost, right? Ghost because it's what you eat, the quality of the air you're breathing, the quality of the water you're drinking. If you had a bad night, if you're socially isolated. So these are things that are more difficult to quantify. But there's clear links between these exposome or social and lifestyle determinants of inflammation and those that are triggering acute inflammation.

9:11So very different types of inflammation. I'd like to say one more thing. When you ask me, well, how can the immune system be beneficial and detrimental at the same time? There's a concept in aging that certain processes that are protective before the age of reproduction become detrimental when you're older. And this is exactly one of those examples where you're mounting an immune response that's beneficial in the case of acute inflammation. In the case of chronic inflammation, cells go into the tissue, proteins go into the tissue, and they cause collateral damage. And that's how we increase the risk of developing diseases in those tissues.

10:00Jonathan Fields: Is part of this about duration also? Because when you describe you get an injury, you have this inflammatory response, it ushers in a whole bunch of other things that are important for a healing process and that sticks around from anywhere for days to maybe on the outside weeks. Whereas when you have this chronic inflammation, as you described, it's just this enduring thing. So is part of this about, this can be a good thing for a short amount of time when it does an immediate job and then goes away. But when these similar things just arrive and stay and never leave at an elevated level, that's where it becomes dangerous?

10:39Jonathan Fields: Or am I making that up entirely? No, part of it is duration. But another important part of it is that the proteins that participate in acute inflammation are not the same than those participating in age-related inflammation. And I want to bring up a concept which is resolution of the inflammatory response. A huge amount of data from Charles Serhan at Harvard has published the different mediators of the resolution of inflammation. If those mediators, and typically these are lipids, the polyunsaturated fatty acids, long chain, the omega-3s and omega-6s, those turn to be very important regulators of the inflammatory response.

11:30And if you have low levels of these mediators, you ought to sustain a cycle of inflammatory reactions that will ultimately cause collateral damage and loss of function in the tissue. These are short-chain polyunsaturated fatty acids and long-chain ones. They come from animal sources. They're very rich in herring and fish in general, salmon. So the omega-3 that most people take as a supplement, they have anti-inflammatory activity by shutting down the inflammatory response.

12:14Jonathan Fields: So I want to get deeper into, I want to tease out a bunch of the elements of diet. Before we get there, there's a term floating around in my head also, inflammaging, that I have heard kicked around. How does this tie into the conversation we're having? I think it was early in the 2000s, Claudia Franceschi put the word out there, inflammation. And inflammation is simply a concept that chronic inflammation increases with age. And it drives many aspects of aging, not only giving you a higher risk of developing diseases, it also ties to mechanisms of aging. Other mechanisms, for example, cellular senescence.

12:59DNA damage, reactive oxygen species production, proteostasis. These are hallmarks of aging that inflammation is triggering. And that's why, you know, Claudia Franceschi from the University of Bologna, I came and coined the term inflammation to try to understand how inflammation drives aging. But it's exactly the same concept that I just alluded before. is the age-related chronic and systemic inflammation that builds up with age and causes tissue dysfunction.

13:35Jonathan Fields: So the obvious question here is, does it have to build up with age? I mean, it sounds like there are a whole bunch of things that we can do to either slow or stop the process, but is there a sequence where no matter what we do, age is going to bring on a certain amount of increased inflammation? It's just, quote, part of the natural process of aging or not so much? In my own research, we found that it's both. It is largely exposome-driven, so lifestyle, exposures, stress, quality of sleep, and all of that, and aging. So aging in and of itself will cause an inflammatory response because you are producing reactive oxygen species, is because you are producing metabolite byproducts, because you're breathing, because you are alive, you are producing inflammation.

14:32Now, there's other studies that have been conducted in different tribal societies, hunters and gatherers, for example, that are not exposed to our industrialized life that we all suffer from. And in these populations, there's no inflammation. aging. So they're protected from inflammation. Even 80-year-olds are doing quite well. They don't have the inflammation that you see in our developed world.

15:02Jonathan Fields: So I mean, the argument from that then would be that if you continue to exist in sort of a modern Western world in some way, shape, or form, it's very likely going to affect the level of inflammation as you age. But if you choose to miraculously entirely opt out of it, I guess the control group is those communities you just studied. If you can actually find people who've opted out of it, that the process actually, it's not genetically wired into us that this has to happen, but the reality of a modern lifestyle is that nobody's going to fully opt out of it. So on some level, just on a practical basis, this is going to be what we're experiencing.

15:44Jonathan Fields: Is that right? Yes, that's actually a first statement. I'd like to say that we can learn from those types of societies and try to adapt our current world to maintaining a life that's as close to as how we evolved, right? Without going into the issue of sanitization and all of that, which I think modern medicine has done a terrific job at saving lives with vaccination and antibiotics and everything else. It also is causing a damage in our microbiome. It is increasing our levels of inflammation. So it's a double-edged sword. I also want to say in those, you know, that's one study looking at these tribal societies.

16:39So how much of that holds in other non-industrialized societies is still unclear.

16:49Jonathan Fields: And we'll be right back after a word from our sponsors. Good Life Project is sponsored by Bombas. So there's this moment every fall here in Boulder. The morning air is crisp. The light goes golden against the mountains. And something in you just wants to slow down, like soft layers and long walks and a warm mug and a good book. The cozy feeling has just arrived, and cozy really does start at your feet. Bombas just launched new suede moccasins, cushy soles, a shearling lining, and water-resistant suede, so a little frost on the grass isn't a problem. Our whole family's sock drawers are basically shrines to Bombas.

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18:04Jonathan Fields: out. The Life Project is sponsored by Hostinger. So when I started podcasting more than 14 years ago now, I remember thinking about building our first website and the project just felt so daunting. I put it off for months and even then it took so long and was just really complicated, but it's also really important because the moment you start sharing your work, people go looking for you. And what they find is the difference between, huh, interesting. And I want to work with this person. Some of my best collaborations started that way. And Hostinger makes that part simple. We're in the early stages of planning a new product right now.

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19:53Jonathan Fields: Visit Ernesta.com and order five samples for only$10, and you'll get$50 toward any rug of your choice. That's E-R-N-E-S-T-A.com. You just mentioned the microbiome. So this is one of those other super buzzy phrases that we've all heard over the last chunk of years, right? The critters, the bacteria, the bugs that exist not only in our gut, but on our skin and in different parts of us that apparently dramatically outnumber the cells in our body. Take me deeper into the relationship between the microbiome and inflammation. Unfortunately, I cannot go too deep because there's more questions than answers in the field.

20:35I can tell you a few things that we've learned. We've learned that microbiome diversity is key to maintaining low levels of inflammation in the body. And microbiome diversity allows for a musing layer in your gut to be thick enough and to filter things and to act almost like as a communication from the lumen of your gut to your periphery. So if that layer of musing gets reduced because you are constantly taking ibuprofen or you're exposed to an ultra-processed diet or even things like carboxymethylcellulose or polysorbate 80 that are everywhere in the ice cream you ate last night, you're wiping out the microbiome, you're reducing diversity, you're decreasing that layer that's protective of musing in your gut, and you're allowing antigens that are in your gut to go and cross that barrier and hit the peripheral blood.

21:48And so it increases inflammation because you don't have a protective layer. Now, specific families and genes of bacteria, I don't think we're there yet. We don't really understand what's inflammatory, what's anti-inflammatory. I just always try to to promote healthy behaviors that will increase your microbiome diversity and feed your bugs, right, with pre and probiotics and all of that. And of course, avoid drugs and poor quality of life.

22:22Jonathan Fields: So we know that diversity matters in the microbiome. Correct. We know that the integrity of sort of like the mucine layer is really important to keep potential inflammatory agents out of direct contact with the blood and the rest of the body. But we're not at a point where we can say, these are the six critters that are the most anti-inflammatory and these are the four that you want to avoid the most. No, there's been a lot of work in the field over the past decade, but we cannot say that for sure, that there's this, you know, go and take these bacteria and increase your levels of this or that.

23:02In hunters and gatherers, they have 300 times more diverse microbiome than an American or even an Italian person. There's been some really cool studies. And I think that's where we can attribute some of the protective forms of lifestyle that you see in these populations.

23:23Jonathan Fields: Yeah. So diversity is really key there. You used another phrase a couple of minutes ago also that I'm really curious about, senescent cells. Is that the same thing as these things that I've heard about called zombie cells, or is that something different? Yeah. These are the same types of cells that react to inflammatory molecules, and they become inflammatory themselves. So they propagate the inflammatory response. They stick around for long periods of time. They don't die. They're kind of an interesting cell type that the field of aging has been focusing on for now over 15 years, maybe a little bit over that.

24:05And they're a key part of the hallmarks of aging as we know them. It's part of the mechanisms of how the biology of aging is driving poor outcomes.

24:17Jonathan Fields: It's funny because I always just assumed, well, these are dead cells that just haven't been processed out of us. But you're saying that's not true. What are they actually? Where do they come from? So they're not dead cells. They're actually living. This is a very conserved response that even smaller organisms develop. If you hit any cell, essentially any cell in your body, with a very strong stressor, let's say in a radiation, that cell, to protect your body from developing cancer, it will become senescent. So it's a protective response. But again, similar to what I said before, there are certain processes that ensure you get to the reproductive age strong and fit.

25:12And then you start to pay the bill because those senescent cells produce inflammatory molecules. They propagate over time and they stick around for many years.

25:24Jonathan Fields: So that's sort of an accumulation with age type of thing. is there a way to get rid of them? That's maybe an overly silly question. No, not at all silly. There's no such thing as a silly question. I want to say there's a lot of companies, and even in the academia, that have invested years and years of effort and money to develop an insenolytic drugs that can specifically get rid of senescent cells. There's a few studies looking at high-intensity training as a way of removing senescent cells in the body. And again, it's a moving, kind of a very fast moving field. Yeah, so high intensity training, meaning working out.

26:07Yeah, and the HIIT training, yeah. Huh, amazing.

26:11Jonathan Fields: So I think I have a better sense of the danger and some of the mechanisms that we're talking about here. In a moment, I wanna get into some of the things that we may think about doing. But you brought up something earlier also, which is if we can't easily see these things, and oftentimes we don't necessarily feel them, we may feel that something's a little bit off or maybe we just feel that there's a general sense of inflammation or a little achy or something like that, maybe some level of systemic inflammation contributing to this. Are there accurate tests for this type of inflammation? Can we go to our doctor and say, hey, can we run this panel?

26:49As part of the Stanford 1000 Immunomes Project that I've been leading for over 15 years, I want to give you kind of a historical perspective of the biomarkers of inflammation. aging, I was very disappointed that we don't have good biomarkers for systemic chronic inflammation. And they're not, you know, basically you go to the doctor and ask, can you measure chronic inflammation? They will probably ask you to do a high sensitivity C-reactive protein. It turns out that when we look at the effect of CRP in health outcomes, it's a very poor predictor of aging. It's a very, very poor predictor of cardiovascular disease.

27:33It's a little bit better than flipping the coin. Your accuracy to predict cardiovascular events is close to 65%, not to mention other diseases that has no predictive value. So I was very disappointed. And one of the focuses of the 1000 Immunoms Project is to identify which sets of biomarkers are best to predict aging, chronic disease, multimorbidity, and mortality. And so we actually published a paper in the year 2021 in the Nature Aging Journal that essentially makes the case for the first inflammatory aging clock. And we call that the I-Age clock. And it's actually currently being commercialized by one of my companies.

28:27It's called Edifice Health. And so you can actually order this online. You can go to the doctor and they can order this for you. So it is currently available, but it wasn't until we developed the test.

28:41Jonathan Fields: So the Sanford 1000 Immunones Project, this was something that you've been involved in for, from what I understand, a good 15 years where you're tracking the immune system of thousands of people over a very long window of time. So it's longitudinal. so you can really see change. Yes. So I've been involved since conception, right? 15 years ago. So tell me about this. I want to know more about the clock. Yeah. So easy. Like you described, in the past, every time I go and get my physical every year, HSCRP is on there. And that's always been pointed to as a marker of like, oh, if this is high, that's a marker of inflammation in your body.

29:20Jonathan Fields: And you're saying, that's really not all that useful. But you do have a new measure that is. Yeah. So in the 1000 Immunomes Project, we measured expression of genes, expression of proteins, metabolites circulating in the blood, cell types of different sorts. And the first thing we did is to try and see if any of these different layers of the immune system are more predictive of mortality, morbidity, and aging itself. We found that proteomics, the data containing all the proteins, was most predictive. And then we applied this nonlinear method, an AI machine learning method, to try to predict aging.

30:02And at the same time, in the loss function, in the function algorithm, call it predict morbidity and mortality. And so that's the first clock of inflammation that is predictive of mortality, predictive of morbidity. You predict frailty. Seven years before someone gets frail, I can take that test and predict who's going to be in the poor trajectory of aging. And so now that became available to the public.

30:36Jonathan Fields: Oh, that's incredible. And this is just something where now if you're going to a physician and you know about, are physicians generally aware of the existence of this test? They're getting more and more aware. So we are a partner of the XPRIZE HealthSpan. It's$101 million for the winner that can slow down aging by, say, 10 to 20 years. And so we're providing all of the immune aging assessment with the inflammatory clock of aging. And I think more and more people are aware that this is available. I mean, that's interesting, right? Because now it sounds like for the first time, we may have access to a benchmark that has a high level of correlation to systemic inflammation.

31:26Yes, exactly. Part of this study we did was in people that were matched for CRP. So they all have lower CRP than one. And so they were sort of protected from a clinician standpoint. And we saw that inflammatory age, our clock, is predictive of heart ventricular remodelings, which is not the best thing you want to see in the heart and arterial stiffening in these healthy individuals that were matched for BMI, matched for CRP, and yet they had increasing levels of IH or inflammatory age that was predictive of poor heart aging.

32:10Jonathan Fields: And that, I think, brings us really nicely to the big question, which is, let's say you are able to find out that you actually have a high level of inflammation in your body, you take this test or through other means, you know, then the obvious question becomes, what can I do about this? And it sounds like there's probably a lot, but before we get into some of the specifics, is there a point of no return? Like if you, if, you know, if you take a test like this, or if you're 40 or 50 or 60 or 70 or 80. Is there a point at which the cascading effects of chronic inflammation over time are largely irreversible or can we always help and do something?

32:58Well, that's a terrific question. I don't think we have the answer for, I tend to think things are largely reversible on the immune system. We've sent people to space. We've worked with NASA for now five years. We know that there is a model for immunosenescence or accelerated aging in the immune system in these individuals. And the first thing that recovers is the immune system. So if there's something that's malleable and that can go back to a healthy, more optimal state is the immune system and your inflammatory response. That said, we don't have hard data on long-term studies to show you can reverse, you can bring it back.

33:43And at some point, there's a no return kind of tipping point there.

33:50Jonathan Fields: And we'll be right back after a word from our sponsors. Good Life Project is sponsored by Nutrafol. So quick story from our house. When my wife, Stephanie, was in menopause, she noticed more shedding than usual. She loves to read, research before trying anything and she landed on Nutrafol. And something like six years later now, she's still taking women's balance formula every day and she has noticed less shedding and more visible thickness. Nutrafol is the number one dermatologist recommended hair growth supplement brand and it's the number one hair growth supplement brand personally used by dermatologists.

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35:49Jonathan Fields: Subject to credit approval, Apple Card is issued by Goldman Sachs Bank USA, Salt Lake City Branch. Terms and more at applecard.com. Good Life Project is sponsored by Vinted. So a few weeks ago, I was going through my closet and kind of realized how much was in there that I hadn't touched in honestly years. Just stuff that I kept telling myself I get back to. And I had this moment where I thought this isn't just clutter. It's a chapter I'm not really in anymore. And I would guess a lot of you know what I'm feeling. That's exactly the situation Vinted is built for. So Vinted is a secondhand marketplace app.

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37:00Jonathan Fields: That's Vinted. So let's talk about some of the contributors. And then, because I feel like the conversation about what might be contributing to sustained chronic inflammation is almost like the corollary of the conversation about what might we do about it? So the way we've been thinking about this is twofold. The first one is establish your baseline. You want to measure yourself. If it's inflammation or if it's your glucose or whatever you're targeting, you want to measure that first. Secondly, start doing things that are very easy to do and that are one size fits all. We will all benefit from having high vitamin D.

37:45We will all benefit from parking a little bit further from when I go grocery shopping and I do a little bit more exercise on a daily basis, right? 10 minutes walk. We will all benefit from that. Having a social connectivity and, you know, the sense of belonging will definitely impact your inflammatory load. And then what you want to see within that inflammatory test is the contributors. there's five proteins that we have identified that are driving most of the variance in inflammatory aging. The first one is called CXCL9. By the way, they can be produced by senescent cells. And this protein goes to your heart and is causing functional issues in putting a very high level to your heart and your vasculature.

38:39If you know there are, for example, mapping compounds to increasing levels of CXCL9, I can give you one example, paraformaldehyde. Paraformaldehyde or uniformaldehyde increases your levels of CXCL9. If you have new furniture at your home that's made out of wood and you have these sticky layers that are able to glue all that wood, you probably have formaldehyde in the air. You're breathing it and you have high levels of CXL9. So you should measure formaldehyde in the air. Then there's another protein called eotaxin. Eotaxin goes to the brain and is being associated with mild cognitive impairment and dementia.

39:31We measure this protein. If you have high levels, there are certain things you can do to bring it down that are specific for that protein. I can just mention one. If you're exposed to air pollution, you will likely have high levels of biotoxin. So that's the first thing you should do is to buy an air filter system. So that's just one example. Right.

39:55Jonathan Fields: So those are two of the fives and one affects the heart, one affects the brain. Does it make sense to walk through the other three just briefly? Yeah, of course. The other three are Grow Alpha. Grow Alpha participates in the entire immune response. So you want this kind of counterintuitive. You want a strong immune system to fight virus and bacteria but you also want to have low levels of inflammation so that the delta, the difference when you get exposed to a virus or other pathogens is high, is big, right? And so Grow Alpha is one of them. You have very important interferon gamma. It's another one that we measure.

40:37And the last one is Trail. And Trail is a really interesting protein because it will sensitize cells to undergo cell death. And in senescent cells, you want high levels of trail to counteract the effect of senescent cells in the body. And so some proteins increase with age, right? You're taxing on CXL9. Some proteins decrease with age, and that's where it gets detrimental. That's what increases your overall eye age or inflammatory age.

41:11Jonathan Fields: So of those five proteins, it sounds like some of them respond to environmental stimulus. Are these also affected by nutrition, by what we eat or don't eat? Yes, yes. Largely affected by nutrition. Just maybe one example that comes to mind is the CXCR3 receptor in the gut. Proteins from gluten like gliadin will bind to the CXCR3 receptor and that will mimic the effect of CXCL9. CXL9, the protein I mentioned before, binds to the CXR3 receptor. It's the same receptor that you have in the gut that binds to a gliadin, for example. And that causes, downstream, that causes inflammation. Correct. So that's another potential mechanism then for, because people often, there's still this debate about gluten.

42:03Jonathan Fields: And some people will say, well, if you don't test for celiac, this is just completely made up. There's no reason for you not to have it. And then there's a spectrum of gluten sensitivity. And you're saying there may be other reasons to think about your sensitivity or whether you want gluten in or out of your diet, but this is one specific one that's directly related to inflammation in the body. Yeah. The fact that you don't feel inflamed doesn't mean you're not. The fact that you don't feel leaky gut, it doesn't mean you don't have a leaky gut. And gluten causes increase in the permeability in the gut, and that increases inflammation by the mechanisms I alluded before.

42:42When you have poor microbiome composition, for example, it's the same mechanism. Leaky gut and translocation of antigens that are usually in the lumen of the gut to periphery.

42:56Jonathan Fields: Let's stay with nutrition for a minute. If we could sort of split that into two categories. more of and less of. If we want to focus on our nutrition to try and reduce inflammation as much as we can, are there a few foods that would be sort of like the big levers where you would say have more of this and have less of that? Yeah, 100%. More of raspberries, blueberries, superpower foods that are packed with great stuff, a lot of fiber to feed your microbiome, not so high sugar content, very rich in polyphenols. So go high as you want with raspberries and blueberries. Strawberries and blackberries, not so much.

43:46They tend to be pretty sugary and not so high in fiber. Fish, just go as high as you want, you know, herring, sardines. One sardine may have about a gram of omega-3. This teeny sardine gives you a pretty high quantity of omega-3 salmon.

44:08Jonathan Fields: Before we get to what to cut, also just question about fish, because so many of us have also heard over the years that fish can also give us exposure to heavy metals. So how do we deal with that? Yeah, we've also heard that it's possibly a solution to eat small fish and then have short lives. They don't accumulate as much. If you go into detail, we are in a very toxic world, exposed to plastics and we're breathing plastics. We're exposed to heavy metals. The list goes on and on. I think the way to mitigate that is by eating smaller small fish and not those bigger ones that accumulate a lot of heavy metals there.

44:55Jonathan Fields: Got it. So let's talk about the less of side on nutrition then. What might we think about having less of? I'm going to give you a very personal response here. Answer. Dairy products that we haven't exposed to during evolution. Grains in general. Of course, hyperglycemic foods and processed foods, that's the thing that you should cut immediately. And then grain-derived oils packed with omega-6, which are highly inflammatory. So if you are using oil, hopefully, to cook and to, you know, kind of dress your salad, you do maybe avocado oil or olive oil and not the other types of grain-derived products.

45:40cut on omega-6. So if you go to nutritionfacts.com and you look for anything you're trying to understand the nutritional components, and you look for omega-6 and omega-3, cut on omega-6, cut on omega-6 as much as you can. Interestingly enough, eggs have a very high content of omega-6. So try to be cautious to not be exposed to so much egg consumption. I think in America, we love eggs. We have them every day on your breakfast. I try not to. And of course, pasta, rice, all those are very rich in calorie intake, and that increases your reactive oxygen species. You're going to have inflammation in response to hyperglycemic foods.

46:31Well, the list, again, goes on and on. I don't know how much time we have.

46:35Jonathan Fields: Yeah, I mean, those are, I think, just interesting starting points. sadly like you're describing some of the things that i love most um which is probably a common reaction and and i think that's one of the challenges for so many of us right because um we look at that and we say like i just don't want to completely cut that out of my life and maybe the answer is like let's just start by like having less of you know like um because there's probably a bit of a dose response here where it's like the more you lower it, the more that's going to help lower your inflammation. It's brutally hard, if not impossible for most people, but eating the things that you want to eat intentionally and in a way that you feel supports you and your health.

47:18Jonathan Fields: You mentioned this earlier too, exercise. Does that affect inflammation in positive, negative ways? Exercise, it's a super interesting field. We've heard that it's the best drug for aging. Building muscle mass is definitely anti-inflammatory. Muscles are secretory organs. We've counted over 300 anti-inflammatory peptides. So it's 100 % beneficial. The older you get, the more muscle mass you should have. The idea of slowing down because of wear and tear, I think it's quite the opposite. You should wear, you should use it more, your muscles and put compression in your bones. That way you can develop resilience.

48:08When you're engaging in high intensity training where you're doing your cardio, you're going to see increases in acute inflammation. That's quite interesting. You have your interleukin-6 that skyrockets because it's kind of reacting to certain stress. You're stressing your body. That stress causes inflammation to go up, but then it should go back down. And the net result is absolutely positive. In the long run, the more exercise, the more muscle mass you develop, I think the better you are at keeping inflammation at bay.

48:47Jonathan Fields: You use the word stress and you just referenced it earlier also. Sounds like stress also contributes to inflammation. Psychological stress, I mean. Oh, psychological stress, yes. Yes, 100%. And that's, I usually recommend people to maybe stop at some point during their busy lives and do 10 very deep breaths. Every breath you take, you're kind of decreasing that cortisol response. We've seen in cancer caregivers that you take the cells out of, say, your immune cells and then you culture them. They're producing massive amounts of inflammatory mediators. You try to knock that down with anti-inflammatory drugs, nothing happens.

49:37And you know why? Because these people are chronically stressed. Your acute stress, I think, is beneficial. Your chronic stress causes the glucocorticoid system to be completely dysfunctional. And what is this? Glucocorticoids have evolved to shut down the immune response. And your cells have receptors for glucocorticoids. When you're exposed to cortisol constantly because you're psychologically stressed, your cells will hide those receptors. That's called desensitization of the glucocorticoid system. And so it doesn't matter how much anti-inflammatory molecules you have in the body, those cells are going to continue to pump inflammatory molecules in the body.

50:29Jonathan Fields: That's fascinating. And even sort of like your over-the-counter anti-inflammatories, it's not going to touch it. They don't work now. So interesting. One other question then, since you brought up this idea of anti-inflammatory medications. One thing that I've been hearing a lot of lately, increasingly, is the off-counter or off-label use of this category of GLP-1s. Not for weight loss, not necessarily for glucose control, but for inflammation. Is there research going on around this or is there actual data on this or is it all anecdotal at this point? No, there is some good data showing that one of the pathways that are involved in inflammation is modulated by GLP-1 agonists.

51:14And so we've even seen in our own data that people on GLP-1 live longer. And maybe the mediation is inflammation. We even accounted for loss of BMI or decreased BMI. is not necessarily linked to weight loss. We believe GLP-1 agonists are acting as general protective agents and very likely anti-inflammatory ones. There's a little bit of data on causation. The inflammasomes, NLRP3, I think it is, which is a main pathway of inflammation, can be modulated by GLP-1 agonists. So that's kind of the only way that at least I found a causal mechanistic relationship between these peptides and lowering the anti-inflammatory response.

52:10Jonathan Fields: So interesting. Sounds like we're early days there, but it's a really interesting pathway. If somebody's joining us and they're kind of nodding along and they say, like, I would love to get that benchmark and find out what's really happening inside of me. because as you said, we often don't know what the level of inflammation is in our bodies. And then they want to do something about it. We've talked about a whole bunch of different levers they can pull. And it also could be overwhelming for a lot of people. Is there sort of like one big lever that also you feel is very accessible for a lot of people that would be a good starting point?

52:44The problem with interventions is that if you don't have a baseline, it's very difficult to judge if your intervention is working or not. So I'd say, you know, measure what you're targeting to change, you know, measuring. And then once you have your baseline, you can introduce very small baby steps, right? I like to say, you know, the law of maximum effort, that it doesn't have to be that you go to the gym every day. It's just, you know, taking the stairs instead of the elevator, parking a little bit further away from the grocery store, and then play, play around physically with your child, with your kids, if you have kids, or with your dog, go out for, you know, 10-minute walk.

53:29That's only 10 minutes of your day, and it extends healthspan by about 15 years. It's pretty dramatic. So that's movement. And in terms of the diet, I think it's pretty straightforward. I mean, I'm obviously biased, but I think it's pretty easy. This is my recommendation. Cook start from scratch. If you're cooking, it almost doesn't matter when you're cooking, you're putting an effort into something that you're creating yourself. If you buy from the restaurant, everything will be packed with plastics. If you're buying ultra-processed foods and you're putting them in the microwave, good luck lowering inflammation.

54:18There's no way you're going to achieve that goal. If you're cooking and you're using olive oil and you're putting love into cooking, again, I'm biased. I wake up at 5.30 every day and start cooking. That's my thing. But I think you're going to be way better off than just buying processed foods and going out.

54:38Jonathan Fields: Love that. And I love that putting love into your food is a major contributor too. I wholeheartedly agree with that. It feels like a good place for us to come full circle in this conversation. I always wrap with the same question in this container of Good Life Project. If I offer up the phrase to live a good life, what comes up? Personally speaking, I'm giving myself more time to surf. I love surfing. It's the one thing that calms me down, that allows me to be with nature. And I saw dolphins the other day. They were just a few meters away from me. I was alone, Ocean Beach. It was just so gorgeous.

55:21And I wish I could do this until the last days of my life.

55:28Jonathan Fields: Thank you. Let's talk about some of the big takeaways here. One thing I keep coming back to from the conversation, It's how much of what ages us is stuff we can actually see and touch and choose, not some abstract countdown wired into ourselves, not necessarily just genetic. A few things that are staying with me also. First, the inflammation test most of us get our yearly physical, the CRP number that David described, is barely more accurate than a coin flip in his words. So a lot of us have been reassured by a number that was never really telling us what we thought it was. And now there's a new, much more predictive test that's available to us.

56:05Jonathan Fields: Second, we talk about those specific proteins that are driving most of the damage that he described. And at least two of them, CXCL9 and eotaxin, are tied to things as ordinary as new furniture and the air that we breathe. And third, things really simple can make a huge difference. Things like a 10-minute walk is associated with roughly 15 extra years of health span, which might be the best return on 10 minutes anywhere in your day. And maybe a fourth, stress is a massive factor. So don't overstress by trying to be actually extreme. Be human and let yourself live and enjoy things. It doesn't have to be all or nothing.

56:43Jonathan Fields: So here's what I do with this. Before buying anything, just get a baseline first. Know what you're actually working with. Then pick one small doable thing that will be enough for now. And do me a quick favor. Share this episode with one person who you know needs to hear what we talked about today. and leave us a review wherever you get your podcasts. It helps us get discovered and bring more people into the conversation. This episode of Good Life Project was produced by executive producers, Lindsay Fox and me, Jonathan Fields, editing help by Troy Young and Alejandro Ramirez. Chris Carter crafted our theme music.

57:17Jonathan Fields: And of course, if you haven't already, go ahead and follow us wherever you get your podcasts so you never miss a conversation. Until next time, I'm Jonathan Fields signing off for Good Life Project.

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