#296 How to Age Slower by Supporting Immunity and Reducing Inflammation | Dr Jenna Macciochi

Dr Rupy: Does my immune system weaken with age?

Dr Jenna: It's going to be yes, no.

Dr Rupy: Yeah.

Dr Jenna: Some bits yes, other bits no.

Dr Rupy: Okay, interesting. Okay. True or false, we have cancer cells coursing through our body all the time.

Dr Jenna: I guess yes, more or less. Yeah.

Dr Rupy: Okay. Reducing inflammation is key to ageing slower. True or false?

Dr Jenna: Yeah, the unwanted inflammation.

Dr Rupy: Okay. Okay. My diet can help me age slower.

Dr Jenna: Potentially, yes.

Dr Rupy: Okay. And can collagen supplementation help my skin stay looking youthful, just like yours?

Dr Jenna: Nice. Not just your skin, but your whole body, because collagen is one of the most abundant proteins. We think about skin, but it's your bones are predominantly collagen, joints, muscles, the lining of your gut. So it's kind of the scaffolding and collagen supplements have these little peptides which help signal to slow down that decline and rebuild the collagen. So skin and whole body.

Dr Rupy: In true academic fashion, you answered a true or false question with a bunch of sentences, but that's all, that's all good. That's what we're here for.

Dr Jenna: We've only true or false. It's like, can't do that.

Dr Rupy: Hi, I'm Dr Rupy. I'm a medical doctor and nutritionist. And when I suffered a heart condition years ago, I was able to reverse it with diet and lifestyle. This opened up my eyes to the world of food as medicine to improve our health. On this podcast, I discuss ways in which you can use nutrition and lifestyle to improve your own wellbeing every day. I speak with expert guests and we lean into the science, but whilst making it as practical and as easy as possible so you can take steps to change your life today. Welcome to the Doctor's Kitchen podcast.

What if ageing had less to do with your genes, your skincare routine or the supplements you take and more to do with your immune system? Most of us think about immunity as something that only really matters when we're fighting off a cold or a flu, but actually, it's quietly working away behind the scenes every single day, shaping how you feel, how you recover and how long you stay well. Our immune health is also constantly evolving and changing over our life cycle from birth to our 20s, midlife and beyond. Our immune system plays a critical role in how we feel, our risk of disease and how well we age. Dr Jenna Macciochi is an immunologist specialising in the intersection of nutrition, movement, mind-body practices and lifestyle with the immune system in health and disease. She's also a brilliant science communicator with a string of books under her name who has a beautiful way of weaving science with story. And in her new book, Immune to Age, she reframes immunity not as a fortress that springs into action, but as a lifelong partner guiding us through the seasons of our lives from the day we're born to our later years. Today, we're going to dive into why inflammation is not just good or bad, it is necessary and how to explain inflammation to someone that you are speaking to regarding an anti-inflammatory diet, for example. How your immune system changes with age and what to focus on at different stages in your 20s, 40s and beyond and if you're looking after a young person, just like I am as a new parent. We also talk about the role of inflammation in infection and stress in ageing and we have a supplement corner right at the end where we talk about creatine, collagen, taurine, peptides, nootropic mushrooms and other things that Dr Jenna is truly excited about. In this conversation, I really feel that you're going to get an understanding of immunity through the different seasons of life and actually what can have a meaningful impact on ageing well, which is something that I think all of us would love to dive more into. You can also follow Dr Jenna on social media across different platforms. You can find the links to all of that in the podcast show notes and pre-order the book Immune to Age. It is a wonderful, wonderful read.

Dr Rupy: We've got a lot to unpack here. First, I just want to acknowledge the fact that I am wearing sunglasses indoors. It's because I've just had Lasik four days ago, so I'm quite photosensitive.

Dr Jenna: This is because you're looking cool.

Dr Rupy: I'm not trying to impress Dr Jenna here. I'm just, you know, just quite, quite photosensitive. Um, look, your book, uh, is incredible and I, I'd love for you to introduce this concept of immune age. Um, you know, is this potentially more important than our chronological age? And another question would be, you know, how do we, how do we tell whether we're ageing well using our immune system? So, so perhaps let's unpack this concept of immune age first.

Dr Jenna: Yeah, I think, um, actually when, uh, it was when the Queen died quite randomly, I started to get really obsessed with ageing and time, more time than ageing. Because randomly came across this online calculator that would tell you when you might die based on things like, it's not scientific at all, but it was just for a bit of fun.

Dr Rupy: Sure.

Dr Jenna: And I remember doing this and then just being like, whoa, I'm like more than halfway through how long I might live on average based on like, you know, my demographic, etc. And then suddenly thinking like, it's time to start living. And that kind of led me down this rabbit hole about longevity. And I was like, everyone's talking about longevity, it's quite a trend at the moment. You've got like the Brian Johnsons, you know, escaping death. And I was like, well, there's kind of been a longevity revolution, but we've, we've kind of haven't acknowledged it. Like we live about 50 years longer than, you know, like our great grandparents or a few generations back. But then everyone I know is really time poor. And so we've got all this extra time, but we're not really doing the best with it. Um, and then obviously interested in, in health and healthy ageing, I realised that the average lifespan in the UK is roughly 80 and the average healthspan is around 60. So you've got like a 20 year delta. Um, so I was, that led me then down the path of evolution and thinking about, you know, we evolved really with this kind of first half of our life being optimised to reproduce, pass on the genes. And some of the genes that, um, help us do that, genes involved in the immune system, the immune system's inflammatory response, they help us get through, you know, those, you know, early years, risk of infection, we're able to fight that off and we get to an age where we can pass on our genes. Some of those genes have this, um, it's called antagonistic pleiotropy. So they're helpful in the first half of life, but they have the opposite effect in the second half of life. So now that we live so much longer, these genes that helped us get to 40, pass on our genes to our offspring, um, are actually unhelpful for that second half. They actually cause this rising unwanted inflammation, which is the immune system's kind of defense response, which is kind of a wear and tear ageing on our immune system. So I kind of got down this rabbit hole of like, what is going on? Like, how does the immune system fit into this conversation around ageing and how we age? And the other idea was really around, you know, evolution optimised us to get to 40 really well, but now that we live so much longer, we kind of have to fight against our evolution. We have to live quite differently. We still kind of live in like, as if, you know, if we get ill, then we'll do something about it. We don't live in like, oh, I've got a good chance of living till I'm 80. I got to start paving the way now. I have to start taking steps because I'm on this really long life course trajectory potentially that, you know, my ancestors never got to experience.

Dr Rupy: So the way and that's a wonderful way of thinking about it. I've never really thought about our lives in two distinct parts where one is purely geared towards reproduction, which if anyone knows anything about evolution is understandable. And then the latter part is like, well, we've already done our job on this earth, so to speak. So we're sort of, you know, we're not reproductive anymore. Um, so we're, we're sort of, you know, we're part of the evolutionary waste basket. First thing that comes to my mind, even though we're not quite thinking about ourselves in that way. Um, so the immune system machinery that we've developed in our younger years to enable us to fight off things like pathogens or viruses needs to be aggressive enough to protect and preserve our life. Yes. But is this the same response in let's say over the age of 50, just an arbitrary number, is that damaging to us? Is this exaggerated immune response something that's responsible in part for chronic diseases that we see increase in, um, in prevalence?

Dr Jenna: Yes, I think that's what, what is starting to emerge from, from this whole picture. And inflammation is really what keeps us alive. It's what has, you know, allowed human beings not to die out because if we didn't have that inflammatory response, we wouldn't survive and pass on our genes and, and evolve. But if you have, you know, an infection, you get like a short, sharp spike in inflammation that's supposed to make it really uncomfortable for that germ so that you get rid of that infection and you recover. And there's a collateral damage involved. So there's always these kind of trade-offs, I think in biology where there's, you know, there's no free lunch. You have a cold, you get lots of inflammatory damage in your lungs, you feel lousy, you know, you're like coughing up, lots of mucus. All those symptoms, that's your immune system and we kind of point to it like the bad guy, like, oh, my immune system's making me feel this way, but it's doing it for a means to an end to remove the germ. And then your body's equipped to recover and resolve that inflammation and then move on. But I think what we have the problem is now that some of those triggers of inflammation are not just getting an infection, it's, you know, the type of environment we live in, the air pollution, the constant chronic stress, the poor diet, which affects the gut microbiome, which can be a huge source of inflammation. And so we have this kind of insidious set of triggers of inflammation that means we're, we've got this low-grade constant wear and tear, this collateral damage that we're never really able to get on top of. And so that's where it kind of all doesn't work in the modern world. So we're sort of optimised for this, um, world that we no longer live in. And so we have to kind of rethink how we go about our lives. One really interesting example was, um, Otzi the Iceman, I think he's called. So this 5,000 year old, um, mummied, uh, man. And I think they estimate he was sort of in his early 40s when he died. Um, and they found that he had really distinct features of atherosclerosis and heart disease, which you wouldn't expect because 5,000 years ago, he was, you know, eating a minimally processed diet. Yeah. Um, you know, he didn't, you know, have a sedentary life, I imagine. Um, you know, he, you know, all of the things that we know now are considered not good for chronic diseases like heart disease and heart disease is the number one killer globally. Even so much so that I feel like most people are kind of numb to it because it's just you hear about it all the time. But he had really, um, these, you know, strong signs of, of atherosclerosis. And they think that that was because he would be exposed to so many infections. He didn't have antibiotics and vaccines and etc. And this constant inflammation in his blood vessels every time he had a really strong infection and then recovered was having this making the, the blood stickier because it's getting ready to clot. It's, you know, having that shear stress on the, the vessel wall. Um, and so that was kind of like a side effect of being able to survive infections. But because he, you know, his generation wouldn't have lived much beyond 50, there wouldn't have been any heart disease. But then nowadays, you know, we have inflammation that we're, you know, low grade all the time. And then, you know, once we get 50, 60, then we start to be like talking to our doctor about our blood pressure and, you know, whether we need statins and things like that. So there's this inflammatory component, which is, is really interesting.

Dr Rupy: I don't think I've ever appreciated that Otzi the Iceman actually had atherosclerosis. And it kind of makes sense, you know, if you're constantly having these spikes of inflammation that are necessary and relevant in response to, you know, pathogens. And you're repeatedly being exposed to high blood pressure as a, as a side effect of that, which is causing that shearing effect on the arterial walls. Your, uh, cholesterol particles that we all have coursing around our body are more likely to become oxidised as a result of the other inflammatory cytokines that are coursing around your blood, then you're going to have this inflammation in the walls, which leads to narrowing, etc, etc. So the one thing that came to mind there is, is the increasing prevalence of cardiovascular disease as an example, simply a byproduct of the fact that we now have medications and interventions that enable us to live longer. I.e. is cardiovascular disease essentially inevitable for a lot of us and it's just a byproduct of us living an extra 20, 30 years?

Dr Jenna: I think in some ways, yes. And I think even if you look at like the centenarians and the super centenarians, they will have signs of this when you, when you look at them, but they, there's some people that manage to control it in a way. So you kind of just delaying these things rather than saying, you know, we're going to completely get rid of heart disease and nobody will ever suffer from this. It's like, no, how much can you kick the can down the road and keep your, you know, arterial walls nice and clean, um, by, you know, diet, lifestyle, etc, rather than saying like, we're just never going to get it. It's somewhat inevitable because you have these, these trade-offs and sort of the longer you're alive, the longer you have this kind of wear and tear, you know, build up, the more you're exposed to these things. So it's, yeah, it's there's always this trade-off. And I think when you make peace with that, you're like, okay, it's, it is just about balancing the middle path. It's not about being extreme in anything, but remembering that the immune system saves our lives, but it can also have this flip side.

Dr Rupy: Yeah, yeah. I, um, I want to come back to this a little bit later because this idea or the sort of, um, uh, the two different camps of delaying versus reversing are sort of coming to the fore right now, particularly on social media where there is a camp of people who believe that ageing and the diseases of ageing are reversible. Um, you know, whether that's with a constellation of existing technologies, peptide technology or gene editing, uh, or some, some things that are further down the road. But I, I'm going to just bookmark that because I, I know that's going to take us like down another road. Um, it sounds to me that this concept of inflammation is sort of critical or crucial to the understanding of the ageing process in general. How, I know you've just explained essentially what inflammation is and why it's important. What's the simplest way that I could explain inflammation to someone who is non-scientific in, you know, in their thinking? They've never really thought about this inflammation picture before. Is there, is there like an analogy or something that you've come across to help? Because it's really, it's really confusing for a lot of people.

Dr Jenna: I think the immune system generally is really confusing. Um, I think, you know, where one place you could start is we can locate most of the systems in our body. Our respiratory system is our lungs. We know where they are anatomically. The, the digestive system is our gut. We know anatomically where that is. The immune system is everywhere. So it's not contained within a, a single sort of place in our body. It's everywhere. And that's for a reason because it's patrolling the body, looking out for things that could damage us. We do tend to think about it in terms of infection, um, as the main defense against infection, but it's also there to defend against damage, um, or, you know, anything that, you know, a toxin, a pollutant, anything that could damage us, it's there to remove and then repair. So you have a whole constellation of different immune cells and they're sort of dotted all over your body. They're really, um, a lot of them will sit at the places where you might have, uh, vulnerabilities in the body. So lining the airways, where you're breathing in potentially things that could damage you, or lining the digestive tract, there's a lot of immune cells there because you're putting stuff in that system all the time and there could be potential for damage or infection. Okay. And so your immune cells, you have these first responders. I don't want to get into all the nuance of all the many types and subtypes of immune cells, but you have these first line responders and they have these what we call pattern recognition receptors on their surface. So they're looking for patterns of things that are going to be potentially harmful. So a bacteria will have patterns on its surface and the immune cell will say, okay, that is not part of me, that is a non-human pattern. That is a potentially infectious or damaging pattern. And they respond with inflammation. So that means that they start spitting out all these different molecules. We call them chemokines, which attract other immune cells or cytokines that have, um, various different properties trying to make the environment uncomfortable for that germ. And they bring in other immune cells that have all different activities, like some of them will produce antibodies, some of them will be able to engulf and destroy, um, a microbe within its, uh, its own self. Um, and it's this kind of warfare that goes on. And because you have all this kind of toxic stuff being produced, you will get some damage and wear and tear in that micro environment. But if it's limited and it's over a short period, then the body's able to deal with that. We've evolved to be able to go, okay, you have this big bomb of inflammation, and then we come in and we like repair. But you also get inflammation when you don't have infection. So for example, if you twisted your ankle, your ankle gets swollen. There's no infection. You haven't broken skin, you know, no rusty nails went in there. But that inflammation is making the ankle swollen and red and painful. And these are all kind of the cardinal features of, of inflammation. And that's because your immune cells will detect damage as well. So when you have that shearing up of the tissue, you have cells that are being damaged in the, the area that you've injured. That's releasing things in a way that the immune system wouldn't normally see. They'd normally be contained within the tissue, within the cell structure. And once they're broken out, the immune cells will rush in there and start doing the repair. So as much as it's about the immune system eliciting inflammation, it's also about the other part of the equation, which is the resolution of inflammation. And the immune system does both. And you have to think of it as this really carefully orchestrated process where you have just enough elicitation to do the job, and then you have the resolution part. And I think we often forget about the resolution part. It was only more recently that that was sort of studied and understood as being a real key part of this comprehensive response that brings everything back to, to normal. Yeah. So we have damage patterns and then we have pathogen patterns. And these are the triggers for that inflammatory response.

Dr Rupy: Okay. That, that makes it a lot clearer for me and hopefully the listener when you approach inflammation, it's not just one binary thing. There are, there are two main, uh, parts of it. And I think, um, you mentioned a couple of times the uncomfortable environment that we're trying to create for the pathogen or part of the healing process. There's a line of thinking around fever and suppressing fever when somebody is trying to fight off a common cold, let's say, or pneumonia. Um, what is the thinking around this now? Should we be taking antipyretics? And I'm talking about adults here to improve our symptoms whilst we're fighting something off, or should we just be leaning into the fever and allowing our body to essentially do the work?

Dr Jenna: Yeah, I mean, I think this is a really good question. And one that often gets a lot of, uh, different opinions, let's say. Um, I think particularly for parents, but as you said, if we speak to adults, generally, fever is seen to be physiological in that it has a function. It's part of the inflammatory response. Those immune cells that have been activated and triggered by some damage or infection, they're releasing cytokines that will act on the hypothalamus in the brain to adjust the temperature of your body. So your immune system is going to your brain and saying, you have to change the temperature, like you have to increase the, the temperature and bring on a fever. So if you think about evolution, like that, that was there for a reason. We know that certain immune cells work better at that slightly higher temperature. So it means you can act faster. And obviously, if you had, you know, a really nasty bacterial infection, you want that to happen quickly. You want to be able to respond fast. And the other thing it does is it makes the germ quite uncomfortable. The germ wants to replicate and cause a big infection and it's struggling to do that when your body temperature is slightly higher. So over evolution, we've evolved to have that reaction. Um, and then we obviously developed drugs like paracetamol, which are antipyretic, which will bring the fever down. Um, and if you go and dig into the literature, you will find that there is a benefit to letting a fever be a fever. Um, and that we shouldn't be bringing it down. And I think the guidance is that these should be used to relieve discomfort, not to relieve the fever per se. So if you're really feeling uncomfortable, you beyond what you can bear, then take the, the paracetamol. That's what I would do.

Dr Rupy: Yeah, it's interesting, isn't it? Because I'm trying to, I'm leaning more into that way of doing things of Yeah. grinning and bearing it and doing everything I can to support my recovery process whenever I do have a mild illness rather than relying on an antipyretic. Yeah. Because I'm, I, I sort of understand that. But then in the same breath, what, what I tend to do is take lots of anti-inflammatory ingredients in my diet, things like broths and onion and star anise. And these are all anti-inflammatory. So I guess if your body is trying to produce an inflammatory response for a good reason, why would we try and add anti-inflammatory ingredients to our diet?

Dr Jenna: Yeah, that's a really good point. And I love that you, you mentioned your approach. Um, and I think to me, this, you know, fever is part of a suite of what we call sickness behaviors. So the last time you got sick, you would always have also have some behavioral changes. You might feel lethargic, socially withdrawn, a lack of motivation to do things.

Dr Rupy: I wear my sunnies inside.

Dr Jenna: Exactly. You just want to lie on the sofa. Your sleep is kind of like messed up. You've got this, you know, intermittent fever. And when we look at that through the lens of the immune system, that is again, your immune system instructing your brain to change your behavior so that you have the best chance of A, getting better quickly, because you're not going to go like, I'm going to go commute to work and spend the whole day in the office, and then I'm going to go to the gym, then I'm going to meet a friend, then I'm going to stay out late and come back late. Like your body is saying like, no, you need to triage the energy into recovery because your immune system is really energetically demanding. So your basal metabolic rate will increase over 10% when you're running a fever. So you need to, your body's basically shunting energy away from, you know, your muscles and all the other systems towards just fighting the infection, which is why you feel tired. And it's also a sign, don't go and do all those energetic things because you need to allow that to happen. And the other thing it does is you feel lousy, so you don't go on the train to work. So you're not coughing over everyone. You're not spreading the germ. So you kind of contain the infection as well, because nobody really wants that, you know, when they meet you in the office at work. So there's kind of like, we don't listen to the sickness behaviors these days. I know I'm the same as a parent, as a working mom, like the temptation to be like, I just go to the pharmacy, take something that suppresses all the symptoms and I power through the day is there. And I think ideally, in an ideal world, we would say to people, you're sick, you go home, you rest and you listen to your body, like really listen and that's going to be the fastest way to get well again. Yeah. But I think whenever I say that to people, they're like, oh, but the job, like, and I'm really not understanding boss or something. So there's always this conflict between like the modern world and like what our biology is telling us to do. But then the other part of your question around the anti-inflammatories, you know, your body's going to be doing that thing anyway where it's, it's releasing inflammation, fighting the infection, which is an oxidative stress. So it's the opposite of an antioxidant. A lot of those things that you're producing to fight off the infection are, um, like free radicals. They're, they're creating an oxidative stress to make that germ uncomfortable. And you could, I think, you know, in the way like you, you need to start nourishing yourself. By the time you get those symptoms, the, the infection's already been in your body doing some damage. And so by taking those in through food, through nourishment, it's a really gentle way of, of prepping for that resolution phase. You know, you're not giving yourself like a, a sort of superhuman dose of an antioxidant that might shut off that inflammation and stop that, you know, proper clearing of the infection. And I think that's where food is a really beautiful way to, to deal with those situations because it's supporting, you know, the natural course of what's happening anyway, rather than being, you know, pharmaceutical, you know, cutting it off.

Dr Rupy: Yeah, it's, it's really interesting because what you were describing there, that sort of struggle between what your body is saying to you and the demands of the modern world is something that I had to grapple with, uh, pretty much every day as a, as a medical doctor, because there is this, um, uh, pervasiveness in having to write a prescription or to deliver some sort of intervention because it's not socially, uh, acceptable to just say, well, you just need to like just let your body do its course. Yeah. And so this is where we have this sort of itch to write a script for, you know, paracetamol for children, for example, or, you know, write the antibiotic or like give some sort of intervention because you're not doing your job if you're not doing something.

Dr Jenna: There's an expectation that you're going to get a prescription or get some kind of intervention that isn't just go and lie on the sofa. Because it sounds very, yeah, we're definitely conditioned to that. And it's something that I've always tried to bring awareness to and just get people to sit with that thought of like, what is our biology telling us? And, you know, there's also, you know, a lot of people find themselves in what I call the viral spiral. So you get cold after cold after cold. And you know, if you imagine like your respiratory tract, it's this really delicate, lacy structure and it's one cell thick. So it's a really delicate barrier because it's designed to optimise oxygen intake. So it needs to be, you know, this huge surface area. If you get a viral infection in there and, you know, that inflammation's like screwing everything up and, and you're, you're the airway barrier itself, the structure is damaged. The recovery is happening beyond when your symptoms stop. You know, your cold is, is finished, you feel fine again, but that recovery is still ongoing. And this is sort of the what, what we used to call convalescence, which is a term that's kind of all but gone from our vernacular. You need to convalesce to, you know, for a couple of weeks maybe after the incident, depending on how severe the infection is, where that barrier is really vulnerable. So you hop on the tube and someone coughs on you and then you haven't quite recovered, you know, you're immediately got another infection. And people are like, oh, what's wrong with my immune system? I, I seem to be getting cold after cold. And there could be lots going on under the hood, but it might just be like, you haven't properly recovered. And so you've got that vulnerability there. Um, and because of the, you know, we always forget about the exposure piece. If you live in a cabin in the woods and you don't see anyone, you're probably never going to get a cold. But if you're living somewhere like London and think of the volume of people you interact with, it's not always just how good your immune system is. It's like how much you're exposed to those germs and something might slip through the net.

Dr Rupy: Yeah. Quick sidebar to kids, asking for a friend with a six month old. Um, so I think there, there is sort of like a bit of a even more of a struggle there, uh, with like whether you treat a child with an antipyretic because you want to stave off the possibility of something like a febrile convulsion, particularly when they're very young, whilst all this at the same time, not prolonging a viral illness and again, like allowing the body to clear an infection as a, as they do. And I, I actually don't know what the current advice is around antipyretics for kids and whether that's changed recently, but

Dr Jenna: I think, and I'd have to check if there's anything updated, but in the nice guidelines, it's similar to adults, it's to treat the distress, not the fever. Um, and that's something I think has definitely been missed, um, in, you know, I know from being a parent myself that there's, you know, it's very easy to reach for the syrup with the paracetamol inside.

Dr Rupy: We can say Calpol.

Dr Jenna: There are others without additives as well.

Dr Jenna: And I think that that's, um, again, we've sort of become habituated to that. And as a parent, you just want your child to feel okay. I've certainly tried to avoid using it. I've never experienced a febrile convulsion as a parent. And so I think anyone who has experienced that would probably, um, it's a difficult call to make. From what I know, and it's not completely clear in the research, the link between the fever and the febrile convulsions isn't straightforward. So it doesn't necessarily increase the risk. Either your child is likely to have them or not, irrespective of a fever. So it's kind of, um, but as a parent, you know, in that moment when they're, they're screaming and you can see how uncomfortable they are. So I think I would use it judiciously, um, and sometimes with my, I make like a elderberry syrup.

Dr Rupy: Oh, do you?

Dr Jenna: And sometimes my kids will, will just want a, like, I call it the placebo. Like they just want something. It's like, oh, can I have the medicine? And I give them the elderberry syrup. It's purple.

Dr Rupy: That's such a good hack.

Dr Jenna: It's a terrible parent.

Dr Rupy: That's amazing.

Dr Jenna: But like, then they're like, you know, they're like, oh, I feel better now. Like instantly. And that's when you know that sometimes it's a little bit of like the TLC. And I guess as a doctor, you must have experienced that. Sometimes your personal care with that patient, how you deliver that information, that's the therapy. They feel seen, they feel heard. You know, and, and the, the medication is literally a sugar pill, you know, that, that they're

Dr Rupy: Not literally, because you're not prescribing pills, but like, I hope not.

Dr Jenna: But that, you know, that, that care is really important, I think, to the, the healing process.

Dr Rupy: Absolutely. Absolutely. And, you know, it, it's, my experience in both general practice and acute medicine as well, A&E, you know, it's, it's, it's so, uh, necessary in both environments. And they sound very different extremes, but actually the way you talk to them, the way you explain things to them, the way you, uh, treat them with medications if needed. And like you, you explain everything about it, the whole process. Like this is the medicine, that's the medicine as well. Yeah.

Dr Jenna: Yeah. I think a lot of people will, um, express how they felt gaslit or unheard or that it's all in their head. And I think that again can be part of their own suffering because they don't feel seen and heard, especially with more nebulous chronic conditions that don't have a clear root cause or a clear treatment path. I think that can be, um, quite important. And it just kind of boils down to that human connection. Like we're all very wired for connection. That was something that I was really inspired when I was writing this book was, um, the, uh, Harvard study of adult development, which, um, was one of the longest running studies, uh, of, of adult development, of, of human relationships essentially, um, what, you know, made people healthy and happy, what gave them long lives. And they followed these people for, for decades, still ongoing now. Um, and one thing that came out top was that social connection is kind of key for health and longevity. And another aspect of that that they found was that, you know, it helps regulate that immune system, it regulates that inflammatory response. And when we feel lonely, we have this kind of heightened inflammation, and this has been shown in studies because we're kind of, we don't have the protection of the tribe. So we're kind of ready and primed for danger or an accident or an infection. And I think that, you know, we're constantly putting out little bids for human connection. And when that's not met, it feels like rejection. And things like ostracism used to be like one of the worst, you know, punishments ever. Um, and then we see that on, you know, things like social media and kids and, and that's kind of, um, all wrapped up. It we feel psychological, but it's all in our physiology, which I just find really fascinating. Like this interpersonal relationships are both good and bad because if you connections can, you can have really toxic relationships with people, but equally, we all need them. We're just always trying to, we're trying to suss them out constantly and feel out people and it's, yeah, it's messy.

Dr Rupy: I, I, I love that. And it, you know, I did want to ask about whether isolation itself is inflammation producing and whether that can have a negative impact on ageing in, in general. Um, but there was, there was something else in what you said there about, um, putting bids out and feeling rejected, which is, I think something that we definitely see in the virtual world as well, as well as in the sort of physical world. I wonder if we could talk a bit more about that and how that relates to ageing. Um, and also how we measure inflammation as well, because I think this is one of the things that people struggle with because they can, okay, maybe understand what inflammation is now that you've explained it to them. Um, but if we don't have like, uh, a, a an actual measure in the same way we can measure glucose levels or our cholesterol or weight on scales, it, it feels intangible in a way.

Dr Jenna: I think when I was writing the book, one of the things that my editor came to me with early on was like, what does inflammation feel like? Just like from a very like layman human perspective. And it made me think that, you know, it's, it's really nebulous. It's really tricky. And I think that's why understanding how the immune system contributes to our broader health and longevity has been really lagged behind because we don't have good ways to measure it. There's no single measurement. Um, and those things that we can feel like, you know, as I mentioned, inflammation has a huge energetic cost on your metabolic rate. So if you're burning that under the hood, like a low smoldering fire, you might feel more tired than normal. But then you might feel more tired than normal because of something else, because you've got a new baby at home, because you're deficient in iron or, you know, there's like a myriad of reasons. So it's very difficult to say that's because of your immune system. Um, but I think those, you know, creaky aches and pains, feeling like sub par, energy, like as long as you're making sure you're doing all the other things and something's still not right, like you haven't got any overt medical conditions or deficiencies that can be corrected.

Dr Rupy: So when, when someone is perhaps experiencing this mild, persistent raised inflammation, what I'm hearing is that these symptoms can be super vague in that it could be a little bit more fatigue, some pain, brain fog, um, maybe even, uh, coming up as a like a mild skin irritation, gut disturbance, like bloating or these could all be inflammation as well as they could be a whole bunch of other things as well.

Dr Jenna: Yeah, or they could be other things and inflammation to be all sort of entangled. And in terms of like measurements, you know, you would really probably have to go and get something quite comprehensive that looks at all your white blood cells. These are your immune cells. But also bearing in mind that taking blood is only showing what's happening in the blood and the majority of your immune cells are in the tissues. So you can't really get in and access there, like what's happening in the lining of your gut. That's quite invasive to go and, you know, have an endoscopy or something. So there's quite broad limitations on how we can measure our immune system. There is something called the immune age test. This is only in research at the moment. It's not a commercial test. Um, and it basically does a kind of comprehensive look at all different types of immune cells, ratios, things like, um, high sensitivity C-reactive protein, which is, um, a marker of inflammation. So if you have an infection, you'll see a dramatic spike in this, but if you have a low-grade inflammation, you'll see it at much sort of lower levels. And, um, you can, you can put all this together. The other thing, I think, is we, we carry these chronic viruses, cytomegalovirus, Epstein-Barr virus, certain herpes viruses. And what we find with ageing is that they basically stimulate one type of, um, T cell called a CD8 T cell, and they cause it to sort of proliferate in a way that's basically a detering from attacking the virus. It's sort of giving it like a stimulus and saying, go off and do that while the virus is then hiding out in our, in our body. And what we see is this ratio of CD8 T cells to CD4 T cells sort of changes over time and it gets skewed. And if you imagine your body as a container, you only have so much immunological space for immune cells. So you have to get rid of some before new ones are allowed in. It's sort of, I guess like a, like the, the, you know, when the way the bank produces money, you can't just keep printing money. So if you have this like cytomegalovirus is this kind of stealthy virus that about, you know, most of us will encounter in our lifetime, it will cause these CD8 T cells to sort of proliferate in a non-specific way. So you end up with a big container of these, and then you have little space left for the immune cells that can actually do their job. So by the time you're sort of in your later decades, you're much worse at fighting off infections just because the space has been taken up by these kind of useless CD8 T cells that were triggered by this virus. So, you know, infectious diseases are always evolving ways to be sneaky and try and like evade your immune response. And this is just one of them.

Dr Rupy: That's incredible. So are there like certain patterns that we can look at in research terms that will give us an indication of whether someone is going to age well or they've got a higher risk of, you know, uh, certain chronic diseases later on down the line?

Dr Jenna: Yeah, definitely inflammation in that high sensitivity CRP. So if that is consistently high or you have, like, you know, going back to Otzi the Iceman, if he experienced lots of, uh, infections, if you have a high infectious burden in your early life, it can actually, um, lead to premature ageing. And that's unlikely in somewhere like the UK. I'm talking about really severe infections, not just having a few colds and stuff, anyone. Um, and then also these stealthy viruses that sort of hang out in our body. And if we get really run down, that's when they kind of peek up and start being problematic and causing these, um, issues where they skew this ratio of T cells. So you can look at something like the T cell ratio and have an idea of what might be going on. Yeah. And the way to sort of keep on top of those viruses, like I say, they're stealthy, they, they hang out in your body forever once you've got it. You don't even know you've got it. I might be sitting here now carrying it. But if you're looking after your body and particularly things like vitamin D is really important, um, for your body to be able to keep it in check. And also high levels of stress or cortisol will sort of allow these viruses to pop up and go, I'm no longer hiding out. I'm going to come out and start, you know, playing mischief again. Um, so stress, vitamin D deficiency, that's where you're going to have this problem and accelerate that sort of, you know, course that would happen anyway.

Dr Rupy: Yeah. And how many of us are stressed and spend too much time indoors and don't take care of our vitamin D?

Dr Jenna: I think a real big, um, revelation for me is when you said that the basal metabolic rate increases, is it increased by 10%?

Dr Rupy: Yeah.

Dr Jenna: Wow, during an illness. And like that alone, given like, you know, basal metabolic rate is responsible for most of the energy that we burn every single day by just normal processes of living and cells respiring, etc, etc. Um, that's a massive increase. So it's no wonder I feel absolutely wiped out when I'm having a cold because, you know, that's the equivalent of doing like a heavy workout, 10% of your, your energy expenditure.

Dr Jenna: Yeah, yeah, it's wild.

Dr Rupy: Wow. Okay. Um, and do you think there will be anything coming in the future that will enable consumers to have a, uh, a more sort of, uh, rigid understanding, uh, or specific understanding of their inflammation levels in the same way we, we do with like, I know, I'm wearing a ring at the moment that is like, you know, measuring my sleep and all that kind of stuff. I'd love it if I could actually measure my inflammation levels. Yes. And determine, okay, well, I'm not going to exercise today, or I'm going to ensure that I've got more anti-inflammatory ingredients in my diet, or I'm going to, you know, make sure I go to sleep earlier, those kind of things.

Dr Jenna: I think so. And I think now that, you know, people are getting quite used to wearables, there's a lot of commercialization in that space. Um, you could have something like a blood sugar monitor, but a version of that is looking at, you know, the blood, uh, inflammation levels. I think with AI as well and like big data, there's going to be a real acceleration in that space. Um, and now that we have this way of measuring immune age, um, which is basically looking at all these different parameters and, and showing that your body can cope with the inflammation that comes with wear and tear, with ageing, this inflammaging concept, but it doesn't lose its ability to fight off infections. So it sort of manages that. So it's kind of able to do its job whilst, you know, you have that kind of age-related increase in inflammation.

Dr Rupy: Do you think, uh, more people in this longevity space are understanding the link between our immune system, inflammation and longevity, or are we looking in the wrong sort of areas currently?

Dr Jenna: I think it's been really missed. Even when you look at things like the hallmarks of ageing that, you know, we now have and they're adding to it all the time. The immune system kind of touches on all of them. Yeah. Uh, but it's, um, I think it's just not been recognized because it's so difficult to, to understand, to measure, to, you know, we don't really have enough data yet. There's sort of easier things to go after. Um, and so I think it's something that we're missing that's sort of dangling right in front of us.

Dr Rupy: Yeah, because so I, I can't recite all, I think it's like 10 or 11 hallmarks of ageing, but it's like, uh, breaks in DNA replication and telomeres and yeah, proteostasis.

Dr Jenna: And I guess if you think about all that, if you basically pile on an increased inflammation, it's going to have an impact on all of those different processes that are hallmarks of ageing.

Dr Rupy: Yeah, yeah. I don't think I've ever thought about it in that perspective before.

Dr Jenna: And I think, you know, with ageing, we do kind of, um, it's, it's, it's a hard thing to study really, because you have a cell that ages. Like right now we're sitting here, we have lots of our cells are dying. Yeah. But on the day that we die, lots of our cells will still be alive, which I just blows my mind.

Dr Rupy: Not to be morbid.

Dr Jenna: Yeah, yeah. But then you have ageing cells, but then you have ageing organs, like each of our organs age slightly differently. But then we're a whole system together. So how do you, how do you measure? It's like a really tricky thing. It's a tricky problem to, to deal with. And I think to study it as a disease has been quite strongly debated because if it's a disease, then it means it's an abnormal process in the sort of true definition. But because it's a natural process, it's, yeah. And then you have the, the time, when do you start studying people to, to understand ageing? Do you start when they're babies and like follow them for 80 years? It's very expensive. Yeah, yeah. Um, and so it's this kind of tricky thing to, to figure out.

Dr Rupy: Do you think ageing is a disease?

Dr Jenna: Oh, I don't know. I kind of went round about a whole chapter where I talk about this in the book. I don't think I really ever formed my consensus at the end of it. I don't think so because it's a, it's a natural process. Okay. But I don't know that dividing it into tiny molecular hallmarks is the way that we need to look at it. And also we, we have historically looked at these sort of diseases of ageing, which is like heart disease, certain cancers. We look at them individually. And so we study like, you know, heart disease as a disease of ageing. But shouldn't we just study the whole organism sort of declining rather than the specific disease? But then what are you going to use in a clinical trial to measure? So there's a lot of challenges there.

Dr Rupy: Yeah, the way we study, uh, disease, I think is, is flawed in many ways because we're limited by, you know, the sort of, um, uh, the rules and guidelines around evidence-based medicine, which obviously they're for a reason. Um, but going back to the hallmarks of ageing, you know, if we've got these individual boats and they all, we all try and repair them individually. Yeah. It seems to me like the immune system or preventing inflammation is just a way to raise all the boats together.

Dr Jenna: Yes, exactly. And then by, by virtue of that, you, you delay some of the sort of declines we see with ageing.

Dr Rupy: Yeah. I think the, definitely what's lacking in that field is really good longitudinal studies because it's really expensive to follow people for long periods of time. And I think when you see a lot of marketing for anti-ageing things, like, I don't know, practices, devices, supplements, it's like, what, who did they study? Like some bunch of young 20 to 30 year olds for a year and they saw certain changes. How do you know that's going to work for your granny who's already got a lot of established, you know, things going on in her body? Um, and so we don't have, we only have these snapshots. And now that we live so much longer, we need to join all the dots because what we need in our 20s is going to be different to what we need in our 80s. And I think that's something that we haven't quite caught up with. Going back to what I said in the beginning, we've got this extra bit of time, but we've kind of not really got our heads around it like, oh yeah, we do actually live a lot longer. We need to sort of adjust how we live. We can't live like our ancestors who were literally like, I might die, um, you know, before my next meal because I'll, you know, how they were living.

Dr Rupy: So, I want to talk about the immune system through life because I think this is a really important concept for people to get their head around. Um, just because we were talking about it, what, what is like an immune trend or, um, a sort of, uh, something that is getting hyped that you think we're overhyped about and we should probably leave on the shelves or to one side rather than getting too excited as it pertains to ageing and longevity?

Dr Jenna: I think the supplement space is really hyped.

Dr Rupy: Okay, in general.

Dr Jenna: In general. I think, speaking of someone who takes supplements as well myself.

Dr Rupy: Yeah, it takes supplements and you know, as a disclosure, I, I formulate supplements. I work in industry. I understand, um, how it works and that products have to be marketed. Um, but there's, there's some things that are sort of overhyped and I don't, you know, I think if you want to take supplements for longevity, then the one, the sort of ones that I would go after is things like vitamin D, omega-3, maybe creatine, you know, the really kind of basic non-fancy things. Whereas the ones that I think get a lot of hype are like, um, you know, NAD, things like that where I'm just like, I don't know how I feel about what the claims that are being made around some of these and it gives off, I don't know, there's a kind of baseline, go after the, the diet and lifestyle, add in the sort of necessary important supplements, magnesium is another one that's come out quite a lot with a link to like a long, healthy life course. But then the real kind of fancy ones with the real great promise, I would just cast a critical eye over.

Dr Rupy: Yeah, yeah. I'm not a fan of NAD+ or NMN personally. I don't think we have enough evidence to suggest that they are useful. Um, particularly looking at the studies that they've done, there's no human trial evidence. Um, we're going to talk about toolkits a little bit later. So, um, okay. So we talked about hallmarks of ageing, we talked about inflammaging, the concept around inflammation. Um, I want to turn our attention to how our immune system changes and develops over time because even the way I think I was taught it at med school, for me, it was very binary. You have different parts of your immune system, different areas where they operate, although, you know, holistically around the body. Um, and that's about it. I don't think I've fully appreciated how the immune system evolves over time from when we are children to our 20s, 30s, 40s, 50s and how that might be different for men and women as well. So perhaps, you know, you could talk us through this wonderful, um, parallel that you have with like seasons and and and how this sort of speaks to how the immune system changes over over time.

Dr Jenna: Yeah, I wanted to make the book have a kind of positive feel to it. And this was again, going back to my my musings about meditating on my own death and how many years I might have left. I was like, oh gosh, you know, this can be quite a morbid space. It can feel quite like, I must not die. I have to sort of have this rigorous, um, you know, protocol for, you know, postponing ageing, death until I'm like 120. And at the same time, I was going through some massive personal life changes, which, um, was kind of influencing, I guess, what I was writing about. And it made me think like, if I'm halfway through my life now, then I get to write the next chapter. Like that agency, I think we've lost in our lives. Like we're kind of outsourcing that to everyone else. And so I started to think of it as, as in seasons. And I obviously big fan of nature and I love, um, that, you know, the way nature just regenerates, that every season has a reason, it feeds into the next one. And I started to think about the life course like that. So, you know, spring is this time of like growth and renewal. It's like the strong roots. You don't see much, you know, above the surface, but the roots are really being formed. And the stronger the root system, then the stronger that that growth will be. Uh, and so this is kind of like going back to, um, when we're born, it's a massive, massively important time for the immune system. And not to scare parents, I'm a parent myself, and it already feels like a lot of pressure. But there's really important inputs in those first few years that will shape the trajectory of the immune system, how it matures. Um, and we already know that we have lots of challenges, um, in kids today that we never used to have, which, you know, particularly around allergies, eczema, food allergies, um, asthma, um, also things like obesity, even things like bone density is much, uh, is not being built in the same way as it was previously. We know that muscle, like bones are where we keep all our immune cells. That's where they're made. They're the factories. Um, and so healthy bones are going to make healthy immune cells that are then going to go out into the world. Muscle is an immunologically active organ. So we need to build up, you know, that that muscular skeletal structure in early life. And I think if you miss that window, you know, if you have a child who's not had the opportunity to be active, who's maybe had a more of a sedentary life and a poor diet, then think of the trajectory they're on. And this is where I think about different generations, like my grandparents' generation didn't have the, um, they just had to be active. That was life. There was no processed food, there was no screens. And so, you know, now we're dealing with this whole new set of challenges that we're just not prepared for. Um, and we're putting kids on a trajectory that's going to be really hard to turn as an adult. If you want to make changes to your diet and lifestyle, you know how hard that is. But if you're habituated as a child through circumstances beyond your control, then how hard is that going to be to change? And I think we've got this kind of huge tidal wave of, of issues that are going to affect all the future seasons of life. And we have to start to connect the dots and not just see that, you know, a child as a one-off, you're like, no, that's his life course now or her life course that's been, you know, set up now, that root system, everything, all those inputs that we're giving it, they have to, we have to do something and it's really important. And health is really about passing the mantle, like we, we sow the seeds that someone else will benefit from. And I think that's what we have to really think about that. What are we passing on to future generations in terms of their wellbeing and their health?

Dr Rupy: Yeah, and I mean, as a new parent, um, I think there's two ways in which you can look at this responsibility. You can get anxious about it and you can really think, oh my god, like I don't want to mess this up. I want to make sure I've got the roots that Dr. Jenna is talking about. I need to make sure that they're out all the time. And then there's the other side, which is like, you have this opportunity to set them up for the, the, the, the best start in, in life. Um, and I think there's two things that you picked up on there that perhaps I'm definitely going to take away because I'm constantly thinking about the gut, right? I'm just like, you know, we're weaning him at the moment. We're like, let's get diversity in. Yeah. He's lucky that his mother has been able to breastfeed, uh, alongside, um, uh, formula as well. So we're giving, you know, some of those microbiota accessible carbohydrates and the, the wonderful additions, um, that breast milk gives. But I don't think I've really thought about, I mean, perhaps it's because he's not walking yet. But I don't think I've ever appreciated the, the bone health and the muscle health as they pertain to immune health.

Dr Jenna: Yeah, exactly.

Dr Rupy: You know, and I think this reframing of muscle from just being something that moves our limbs to actually being, uh, an immunological organ, but an organ itself is, is something that we, we need to appreciate, particularly in younger life.

Dr Jenna: Yeah, completely. And I think you're right to say about the gut being the hub. Um, it really is a hub of like immune development. And it starts with, you know, within the womb. And then obviously, you know, we, there's lots of information now about the root of birth being important as a kind of seeding event for the baby to be seeded with the right microbes. And then the breast milk contains, as you said, these, these carbohydrate structures, which are not necessarily to feed, give the baby nourishment, but they're fertilizer to bring out the right microbes in the gut. And actually the baby's gut is, is, you know, we talk about diversity, but a baby's gut is not diverse in the very early stages. It's meant to be quite, uh, uniform. It's got this bifido flora. And these bifido flora, uh, are really important for giving a signal to the immune system to create this balance between what we call the TH1 and the TH2. So the TH2 is the one that can be a bit problematic and cause allergies. And the TH1 is more the one that's fighting off, you know, infections, bacteria, etc. And so if we don't get this kind of input right, then we can end up with a skewed TH1, TH2, and then that may lead to allergies. It's not a definite, and I would never want parents to take away from this, like I must do these things perfectly. Um, but I just think if we gave parents more information about why these things are important, then perhaps it would help, um, get support for, for things like breastfeeding. Yeah. I know having premature twins that breastfeeding was really challenging. Uh, I was quite on a mission to do that despite the challenges, but, um, I think because I knew how important that was for their immune system. But I don't think people are informed. And I think if we give them that knowledge, they might be like, okay, I'm going to give this a try and we put support in place to help parents to do that. That would be really important. And it's not the be all and end all. It's part of a whole suite of things that are, are going on for the child. But we just with allergies being really important, uh, and a huge challenge. And then I think we got, we made a massive mistake. You know, we told people to avoid giving your child the allergen.

Dr Rupy: A professor Gideon Lack, who's, who's done some of this seminal work in this area. I don't know if you've spoken to him.

Dr Jenna: I haven't spoken to him, but we, we are trying to get someone to talk about, um, this very topic because obviously it's very close to me, but yeah.

Dr Rupy: Yeah, he's amazing. Uh, amazing guest. And, and he was, as a young, uh, doctor and doing research was really like the person who was coming to, you know, doing some animal experiments, I think in the very beginning and saying, this is what I've noticed. Um, when we expose them to these things early on, the immune system creates tolerance. And yeah, because we got so worried about, um, peanut allergies, you know, in the 90s, it was like, don't expose your child to peanuts, which actually backfired and it was like, oops, we've kind of done another.

Dr Jenna: And it's still ingrained. This is the thing. It's still ingrained in a lot of people's heads that, oh, I need to be fearful of these allergens. And you can understand why because of, you know, the, the, the drastic things that have happened when certain kids are exposed to these allergens. But, um, yeah, retelling the story and actually introducing allergens whilst it sounds counterintuitive from the perspective of the immune system and actually training your immune system to tolerate these different ingredients. It's, it makes total sense.

Dr Rupy: Yeah, exactly. And there's the, the connection with the skin as well. So your immune system in those early years has to see the allergen through the gut because the gut is this what we call a tolerogenic environment. It's learning to tolerate things that go in that route because generally the things you put in that route are stuff that's safe, like food. But then if your immune system sees that allergen through the skin when it hasn't yet been given through the gut. So for example, if you never give the child peanuts when they're very, very young and they start weaning, but yet they're given some topical cream that contains like a essence of peanuts, peanut oil, the immune system seeing it through a different route, which can actually lead to a really strong food allergy later on. So this is called the dual allergen hypothesis. So it's only something that's been recognized fairly recently. So it's another complex layer to it. You're thinking, what am I putting on the baby's skin as well? Yeah. Um, and just making sure that that tolerance route is through the gut. And so that diversity really early on in weaning is really, really important.

Dr Jenna: That's so, that's so interesting because I was literally having this conversation with my wife as we're introducing allergens into his diet. We've ticked off three. We've done egg, uh, we've got peanuts and I believe we've done fish. Um, and so we're going to add some soy and he's a little bit intolerant to dairy as we found out, but, um, hopefully that will, that will pass in future years. But I remember having this conversation with her about peanuts because she was like, oh, I ate peanut like on peanut butter on toast around him all the time. There's probably some peanuts that have gone on his skin and he's probably fine. But now I'm thinking I've done the wrong thing.

Dr Rupy: Yeah. It's like a dual, what's it? Dual allergen hypothesis.

Dr Jenna: Dual allergen hypothesis. Now I'm like, oh, that was probably the wrong thing to do.

Dr Rupy: Yeah, and it just, it shows that we've got this sort of lag in understanding of our immune system. Like it would have been great if we'd figured this out like 50 years ago and we could have, you know, prevented this explosion in peanut allergies. But it's, it's a challenging system to understand. And so it's, yeah, we need to continually like piece together the information. And I think it's, it's a new discipline as well. Like it branched off of microbiology, the study of microbes. So it's relatively young amongst all the sort of, um, disciplines. So, yeah.

Dr Jenna: I love it. Okay. So spring, modern childhood, setting us up for, you know, adult disease. And there is an opportunity to retell the story. And I guess, you know, within that toolkit framework, it's getting them, you know, exposed to allergens early, getting them outside, getting them active, limiting screens, I'm assuming.

Dr Rupy: I think I'd frame it more as like the habits that you want them to take forward. You know, we can, and I know as a parent, we can easily have those moments where you're like, I just need a like a bit of respite. I just need a break. Like stick them in front of the TV or, you know, give them the iPad or whatever it is. But just think about how frequently you do that and then does it become habituated? Because when they're 15, 16, 17 and an adult going off as a young person on their own, if that's been normalized, that's really difficult to undo. Whereas, for example, even if your kid is not eating the tomatoes, I put them on the plate, like continual exposure. It's normal to have like a variety of vegetables on your plate.

Dr Jenna: Even if they eat around it.

Dr Rupy: Yeah. In fact, yesterday is Easter holidays and my my daughter said, can I make lunch by myself? And I was like, okay.

Dr Jenna: How old is she?

Dr Rupy: She's 10. She gets the biggest plate like this out the drawer, covers it in spinach. I was like, okay. She then like chops some parmesan, puts that all around it, olives, and then a yogurt in the middle. And then she's like, Mommy, can I have some chocolate?

Dr Jenna: What?

Dr Rupy: And I gave her a little bit of chocolate. She put it on top of the yogurt and she just took it off into the garden.

Dr Jenna: That's brilliant.

Dr Rupy: Very strange.

Dr Jenna: Wow.

Dr Rupy: But she's got her greens in.

Dr Jenna: But like, yeah, she's sort of used to seeing spinach on her plate. And so I kind of just, I, that's how I approached it. It was like, I'm going to habituate them. They see what I eat, like role modeling, like I've never done like separate meals for kids than adults. Um, I've never done like, you know, I won't cater to one of them saying, oh, I only want to eat plain pasta tonight. I'm like, no, this is just how we eat. This is it. And also create your own food environment at home. Like there's 10. So when I take them out to parties or they're exposed to adverts, the supermarket, you know, they want all the stuff that's got all the advertising that I might not necessarily want them to eat. I don't always stop them if we're out and about with friends in a restaurant, etc. But there's a food environment that I've created at home that, um, is very deliberate. So if I don't want something to be in the house, I just won't buy it. And they're very used to that now. And I think that's, you know, where we have to realize that when we go to the supermarket, these food companies don't care about your health. Like you have to kind of cast a critical eye on the marketing. It's really hard. Um, and obviously there's like socioeconomic factors in there too. But, um, yeah, I think think about the habits you want ingrained and just keep pushing that until it's part of normal for them. And then hopefully they take that beyond.

Dr Rupy: Beyond. Yeah, yeah. I'll have to update you in like five, 10 years.

Dr Jenna: I'll give you an update on mine as well.

Dr Rupy: How do you think about sugar and the immune system in, in kids in, in particular? Because that's obviously quite a hard one with, you know, food companies and what they see on online and, and on TV.

Dr Jenna: Yeah, again, I always try and come back to the diet pattern as a whole. So if they're at a birthday party and they're going big on the sugar, I'm like, I'm not worried because I know that across the course of that week, the pattern has been a certain way. So it's sort of thinking about the pattern rather than hyperfocusing on one thing. And I think whilst having loads of added sugar is not going to be great for things like the teeth, for oral health, things like the microbiome, particular sweeteners might not be very good for the microbiome. It's thinking about the how much they're having that and then that will sort of give an indication of the implications. And also, you know, just, um, the, you know, being sedentary as well and it's, it's contributing to the overall calorie intake, um, which, you know, kids are just not meant to be sedentary. They're meant to be moving around.

Dr Rupy: Yeah. It's a really good point actually, because I, I think we forget about the pattern over the course of a week or a month. And even if I examine my own diet, I barely have any added sugar day-to-day, but there will be days where I'm getting dessert because we're out or, you know, it's someone's, someone's brought around some cake or whatever it might be, uh, or we're testing something in the studio, although like most of the recipes in the Doctor's Kitchen are very low in sugar at all. But, um, you know, I, I like, I make allowances for myself and I've normalized that. And I think if you can model that and get your kids to model that, that's a much healthier way of approaching sugar rather than a blanket restriction.

Dr Jenna: Yeah.

Dr Rupy: So, yeah, no, that's, that's a really good. Because in my mind, I was like, Raphael's not getting any sugar for the first five years of his life.

Dr Jenna: I think definitely like that when they're kids and when they're really little, you have much more control over them. Whereas now, like they'll go to parties, I'll drop them off, or they'll go to friends' houses and sleepovers and I'll drop them off and I've got no control. Sure. And to say like, you're not allowed to do XYZ and all your friends are doing it. I think that could have more of a negative implication than just letting them experience it. And sometimes, you know, my daughter will be like, oh, they ordered Domino's and I just don't like that because it give me a tummy ache. And I'm just like, okay. So she's, I'm trying to get them to tune into how they feel. Like if you're going to have that type of food and then a few hours later, you're coming to me saying, oh, I feel a bit, getting them to join the dots and then they're getting that intelligence from their own body, which again, I think is something that we can miss quite often.

Dr Rupy: Yeah, absolutely. Okay, um, let's move into autumn. Which is where I am. Which doesn't sound great, but, um, yeah, like 40s, I'm turning 40 this year. Um, this is where I think like there's, there's a real crux period here, right? Where you see the potential downstream effects of the, the spring and summer time.

Dr Jenna: Yeah, I think this is, this is when you have the wake up call and you're like, oh, yeah, I wish I had started that earlier, done that earlier. And I think that if you're at all thinking that, then you just have to start whatever it is that you wish you'd done earlier. That is your calling just to start. And I think it's, if we go back to the seasonal analogy, it's like harvesting. You harvest all that wisdom. Don't berate yourself. Take the learnings and be like, oh, well that was all meant to happen to get me to here to suddenly have the light bulb moment to go, aha. You know, um, you mentioned that people in the summer years don't tend to drink as much as maybe when I was there. Whereas I think I see the opposite, um, in the 40s is that people have a lot of cognitive dissonance around alcohol. And they're not even open to experimenting with drinking less because it's, it's a real crux that they, they really enjoy that. And I think, uh, in the book I call it the midlife gut.

Dr Rupy: Oh, okay.

Dr Jenna: I've spoken to a lot of people, like parents at the school gate and they're like telling me about all their gut problems and they're like, but I eat so healthy. And I'm like, that's great. That's great that you eat healthy. I can't tolerate anything. And I'm like, that's the decades that happened before that got you to where you are now. And it's like, the people are very confused. I eat healthy now, but you maybe didn't for, you know, several decades before. And so that's why we have to start to link together all the seasons and realize that each one is a preparation for the next one.

Dr Rupy: Yeah, yeah. I love that. Um, and I guess if we're talking about the shifts in our immune system, what's going on in this, uh, period of time? Like how, how is our immune system different at this point?

Dr Jenna: Well, there was a recent study that showed that we, we don't age linearly, but in two kind of steep upticks. And one is in the, in the 40s. And I think that is when, you know, we're kind of at that tipping point in evolutionary terms between the first half of life where all your genes are optimizing for reproduction and the second half of life where some of those genes now have the inverse effect, um, and actually can be quite pro-inflammatory. So you see a lot of shifts, you see the consequences of this. This is where things like monitoring inflammation might be more important, dialing in the real kind of anti-inflammatory diet and lifestyle might be more important. So the things that you got away with in the earlier seasons don't apply now. And now it's like, now you're really preparing for those later decades because those are the ones, you know, age 60 and beyond where most people, I think it's something like only 10% of people will get to the, to that stage without a chronic condition. And then you have the whole, only 10%?

Dr Rupy: Yeah, I think there's a study done in the US, um, uh, population, maybe this year or last year. Uh, and you know, then you're talking about having polypharmacy to manage different things and they all have side effects and, you know, so now it's like, okay, the shit's got real. We've got to like, um, really dial in and, and a lot of people reach that period where they might not have an exercise habit. They might have like put on a bit of unnecessary weight, like this is where it's all starting to, to come, come out in the wash. And it's challenging because, and I wrote about this in the book as well from a very personal perspective because you might have ageing parents, like, um, young children, uh, financial obligations, like a mortgage, like it's like a really difficult period in life. And I can really have a lot of compassion for people who are struggling. Um, but it's like, your, your biology doesn't care that you have all this going on because, you know, you have to kind of prioritize the things that are important. And I think this is where I really started thinking about time and how we're all so time poor. And it's like, well, actually, what do I want to use my time for and be more intentional about time? Um, and I've always had a kind of on-off meditation practice, but I was like, now is the time to make time to do, which is essentially sitting and doing nothing, isn't it? Which feels, which is such a luxury. I know, you're really busy. You're like, I'm just going to sit down and like, you know, be and and it, you know, doing a lot of meditation over the last few years to just sort of navigate some difficult times. I was like, my brain is either like ruminating on stuff I did in the past that I wish I hadn't done, or it's like fast forwarding, like a time machine to like what I'm doing next and all the, you know, playing out scenarios that haven't even might never happen. And it just made me realize you only ever have this present moment and just being more present in life gives you a better quality of life. And that was when I brought in this additional dynamic of you've got the lifespan, which is how long you live, the healthspan is how healthy you are until, you know, your health deteriorates. And then you have what I call the soulspan, which is just, you know, living in a way that fills your cup. And that might not be, you know, anything spectacular. It might just be like, you know, coming home from work and just observing my kids like, you know, messing around, not doing anything. Like we're not, it's not a big event, it's nothing. It's just like pottering about in the kitchen or playing in the garden or something, just that kind of garbage non-time, but really observing it and being present. And it's really quite hard to do. At least I find it hard to do.

Dr Rupy: It is, it is hard to do. And it's, like there's so many things that come up there. Like for, for me, when I was taught how to meditate, um, by a wonderful person, um, in Sydney, who's unfortunately no longer with us. Um, Tim, he, uh, I remember asking him a question about good and bad meditations. I was like, look, sometimes I sit down and I'm just like in flow and it's great and I, you know, empty my mind and other times I'm just like what you're description was thinking about things I've done in the past, things I've done in the future, what I'm going to do later on that day. And I was like, how do I make sure that I have a good meditation? And he was like, it's not about having a good quote unquote meditation or a bad meditation. It's about meditation. It's about the process and carving that time out. And actually the observation that your mind is racing from thought to thought is in itself information that you can then take into your day. And I think another element that's very personal for me is that where most people have this realization about gut issues or their first chronic disease or whatever in their 40s and 50s, mine came in my 20s. So when I had my cardiovascular condition, my atrial fibrillation, I was 24. So I had this realization that I'm now grateful for because it changed my relationship with diet and exercise and, uh, even things like alcohol. I wasn't a big drinker, but like I certainly was drinking way more than I drink now. I barely drink. Um, and it sort of like allowed me to seed, um, the, my gut essentially, but also like a, a lifestyle that's very easy for me to, to maintain aside from the fact that I've got a newborn. Um, and I think this time where people have midlife crises, I describe my currently as a midlife moment. It's not a crisis. But it's, you know, we have all these different factors, like you just saying your mortgage and, you know, you realize that you get to a stage in your career, particularly in medicine, where it's like, oh, I've become a consultant. I've got to the pinnacle of my career. Now what? And a lot of my colleagues are definitely going through that right now. And you can just see where the anxiety and the depression and the, um, you know, might not be a, a clinical state of mental, uh, illness, but it's definitely simmering in the background and at least a lot of, um, lack of clarity or lack of purpose and.

Dr Jenna: Yeah, kind of mental anguish.

Dr Rupy: Yes, yeah, suffering.

Dr Jenna: Yeah.

Dr Rupy: And I think it's setting yourself challenges is really important. I mean, my midlife moment this year is going to, uh, you, I, I'm treating the midlife moment through doing things like, uh, sets of challenges. So I've got like a physical challenge, which is I want to be able to do something called a Murph. I don't know if you've ever done CrossFit?

Dr Jenna: No, no.

Dr Rupy: Okay. So there's a CrossFit workout where you do a mile run, uh, 100 pull-ups, 200 press-ups, 300 air squats, and then another mile run with a weighted vest. And I want to try and do that under 40 minutes. I want to do my first duathlon. And I'm also going to do a silent retreat. Um, and that's probably the one that I'm most scared about.

Dr Jenna: I know, I was going to say. The other one's fine. No problem.

Dr Rupy: The physical stuff's fine. I can deal with that. I can go through the pain of that. But the boredom of not reading anything, listening to anything.

Dr Jenna: Sitting with your own thoughts.

Dr Rupy: Yeah, just sitting with your own thoughts. That is, observing your mind.

Dr Jenna: Yeah.

Dr Rupy: It's like a forced meditation. No phone, nothing. So I really think like these, uh, antidotes to modern life, like, you know, silent retreats or meditation, if you can, you know, fit that into your day-to-day, are necessary. Yeah. You know, from an inflammation and immune perspective.

Dr Jenna: Yeah. I think the midlife moment, I really like that. It's, it's, you know, you get to write your next chapter. And reframing stuff that you might be disappointed about that you did in the past as sort of just learnings. I think that was just such a big, important moment for me. And meditation, like observing your mind, like I, I feel like I've meditated on and off for years, but every so many years, I just have this moment of like, oh, I get it a bit more now. Uh, which is always kind of a weird moment. I'm like, oh, I see this whole thing differently and now I understand the why. But just observing yourself whizzing around like time traveling is just really important because it's information, as you say, it's like a feedback. And then when you go to make a bad decision, not necessarily a bad decision, but you go to do something that you know isn't going to support your mental, physical health, you have a bit of more agency over that decision just because you're able to sort of observe your mind and see where it's going. And I think that is quite valuable, particularly from your 40s and beyond, because you can't just have youth on your side and say, oh, I can bounce back from this. I can, I can wait till tomorrow. You know, that feeling that we're somehow in the prelude, like it's not the real act yet. That, you know, we have to move that aside and just be like, this is it. Like every day we have is just the real thing and we have to just enjoy it and be aware and take all the moments and all the learnings and just feed that forward in a life that we enjoy. Yeah. Um,

Dr Rupy: Uh, obviously for women, this is a time where there is a rude awakening in some cases, in many cases. Um, how do the physical changes and hormonal changes affect immunity at this stage?

Dr Jenna: Yeah, this is really huge because of the relationship between the sex hormones and the immune system. Um, our immune cells have receptors on their surface for the sex hormones. So they are influenced by, many women will feel that across their menstrual cycle. Um, you're more susceptible to infections in the second half of the cycle. People get this kind of what we call the period flu where you might feel a bit more ill and unwell. Um, it's an inflammatory process, the the whole shedding of the lining of the womb. So you have this kind of monthly cyclical process. And then with, um, the perimenopause period, this becomes erratic. So something that's been quite cyclical and rhythmical becomes very erratic, which means the inflammation that's associated with that can be quite erratic. And then the menopause event itself is kind of the drop off a cliff of these hormones that have been with us, that have been guiding the immune cells to do different things. And we see menopause as being a bit of an inflammatory event. Okay. And so it's really important for women in this phase to dial in that sort of anti-inflammatory lifestyle. Okay. Um, it's kind of the most vital thing they can do. And I think where, whereas it might feel like your body's kind of being hijacked and something that's become so rhythmic has become really erratic, then you do reach for the crutches because you're maybe not aware of what's going on under the surface. And so, you know, alcohol, I think tolerance of alcohol really changes. And that can be to do with how your body metabolizes estrogen and and alcohol in your gut health. If you're struggling with gut health, you know, and you're not getting rid of those hormones, um, when you're meant to, which, you know, they're being excreted through the gut. Um, I think that, you know, infections, things like heart disease risk jumps massively for women. Um, and it shows up differently in women and a lot of what we consider the classic signs of heart disease are more commonly observed in men. So people might not be aware, they might not be going to talk to their doctor about it, you know, keeping an eye on, on these things. Um, and so I think that's something that isn't really talked about in the menopause space. And I get texts a lot from friends going, what do you think of this supplement? It'll be like the menopause supplement. And I'm like, you know, we're still kind of seeking the solution. And when you look at menopause, I don't know how many symptoms there officially are. It's 30 something. Like a whole plethora of symptoms. And, you know, to think that there's one solution in one bottle to make you feel better, I think we have to get out of that mindset and we have to look at where do we need support? Is it that our sleep is struggling the most? Is it that our gut is struggling the most? Is it our energy levels? You know, where are our symptoms the worst? And then what can we maybe do to support that in a really personalized way? And I think that comes from really knowing your body and having that sort of intuition and wisdom, which I think as women, we have a heightened intuition, but we drown it out with sort of second guessing ourselves. And having a menstrual cycle across the life course is a good opportunity to learn about that. So tracking your cycle, learning what your body does, how it feels, seeing it as a vital sign can sort of prepare for that period of menopause. And then I think things like community, like having, you know, we see so many advocates online, helping people exercise during menopause, like online, um, um, workouts and stuff. And I think the acknowledgement of muscle mass and bone density and how important the hormones are for those. And as we've mentioned earlier, those are really important for the immune system too. I think that's really, really crucial. You know, most women in that phase of life, they might have young children, they might be at the top of their career. They have like a lot of, um, responsibilities that they hold. Uh, and now is the time where you can't afford not to put your health first, even though it might feel like you come last. I think as women, we always put other people first, like be giving all the time. And it's like, the best thing you can do for you is also to look after you and prioritize you so that you can continue to give to friends, colleagues, children, dependents, whatever it is.

Dr Rupy: Yeah. That's, that's amazing. And it, I, I'm almost embarrassed to admit that I haven't really appreciated the menstrual cycle as, uh, somewhat of an inflammatory event during the shedding of the lining. And I guess if we think about that as an inflammation producing event, you can begin to understand the varied constellation of symptoms that people have, including things like PMS, for example. Because if you are raising the inflammation, we know that inflammation is related to mental health issues, depression, fatigue, etc. So it begins to make a lot of sense. And maybe this even opens up the world of, okay, what practices can we do to dampen down inflammation? And one of them that you were just talking about from the perspective of menopause was exercise is very important. We know the, uh, the hormones that are released by muscles when we exercise them, we have enough lean mass can be anti-inflammatory. Our bone health is obviously very important. The whole process of exercise is anti-inflammatory. So it, it kind of gives us some, uh, indication as to why some of these lifestyle practices actually can be useful in a lot of cases.

Dr Jenna: And I think just, you know, I'm, I'm sort of obsessed with the seasons, which obviously comes into the book, but I'm also obsessed with the sort of cyclical nature of things. We don't have to do the same thing all the time. We can adapt and flow with the season of life or things like the stage of the menstrual cycle. There's a lot of discussion online about the best time to exercise and across the menstrual cycle. And actually, if we teach women to feel intuitively, like I know that if I want to go to the gym and get a PB, it's got to be like not the luteal phase. Sure, yeah. But if I want to go and work on technique, but I'm maybe not going to lift as heavy, then I'm going to do it in the luteal phase where I don't feel at my strongest. And so it's getting people to have the agency to adapt rather than feeling like they have to do something textbook. It's great to have studies and it's great to learn. And I think we haven't, um, got enough information. We haven't studied this enough. But also that intuitive part, because I've spoken with a group of women and someone would be like, oh, I, I feel fine across my whole menstrual cycle. I exercise the same. And then other people would be like, oh, I just, you know, I go to swim or whatever it is or run and I just can't, you know, get the same, um, uh, power, energy, whatever it is. And things like progesterone affects your breathing rate, which I trained as a breath work practitioner a few years ago. And that was one of the things I found really profound. So you have a kind of basal breathing rate and rising progesterone in the luteal phase will raise your breathing rate. So you're breathing higher, uh, a number of breaths per minute. And breathing has an energetic cost. So there's an energetic cost to breathing. So the lower you can keep your breathing rate, the more energy you have available for other things. But that means like when I go for a run, I always found that I could never run as fast at certain times of the month. And it's because you've got, you know, you're breathing faster, you're just like the whole system wasn't as efficient. And that was my experience. It might not be the same for other women. But yeah, there's all these kind of nuances that you don't, you don't really.

Dr Rupy: That is amazing. That is amazing. Yeah. And it's so, you know, it's, it's so much more vivid for women who have the monthly cycle. But I guess, you know, even from person to person, the circadian rhythm, like when, when you should be pushing your hardest to get that personal best or, you know, the progesterone and breath work is blowing my mind. I have to look into that.

Dr Jenna: It's just that, uh, the science is amazing and I love the science and I love data, but the intuition is also amazing. And you kind of just fuse those two together. What does your own body and body intelligence tell you? And how is the science kind of supporting that and making sure you're not kind of like misinterpreting something or it gives you more information to explore and apply to yourself.

Dr Rupy: Yeah, yeah, absolutely. Um, let's move into winter. Winter is coming for all of us. Um, you, you talk about this like, where we talked about it at the start of the pod where we talk, you know, this poetic paradox of what protected us in the early stages of our life or the earlier parts of the year, now potentially are the reason or the source behind many of the conditions that afflict us later on. Um, and I asked you at the start about like whether the immune system weakens or declines with age. Maybe we can unpack this sort of, this idea and whether that's, that's, uh, truthful or or there's more of a nuance.

Dr Jenna: I guess it was a, yeah, it's hard to give a straightforward answer. But the inflammatory response tends to become greater. So you have this kind of smoldering fire that becomes bigger. So I guess that in some ways that gets stronger with age. And that could be because it's trying to protect us from infection, because the other part of the immune system gets weaker. So this is where we have what we call immunosenescence. So senescence is to senesce, to, to become old. And that happens to all of our cells. They senesce. Um, but the process of senescence is basically the cell loses its ability to be itself. And instead, it's programming kind of gets hijacked and it starts to spit out inflammation and, and kind of be a bit toxic. So it's like a pollutant. So they say, you know, if you have a, if you find a gray hair, you've got like one of these senescent cells and it pollutes the environment. So you get a whole bunch of gray hairs in the same environment. I don't know how true that is.

Dr Rupy: Is that true? I was going to say.

Dr Jenna: It's a sort of analogy to think about like, you know, as a cell senesces, becomes aged, it pollutes the surrounding environment and kind of causes ageing of the cells around it. Your immune system's job is to clear up these senescent cells. So it's like a constant pruning. If you imagine you have a plant or a tree and you're pruning off the brown leaves, you know, as they come and that leaves space for new growth. So you have senescence happening, you know, all through the life course, but obviously it's gradually increasing towards the winter years. And your immune system prunes off these senescent cells with time. But the problem is your immune cells start to senesce themselves. So their ability to do this pruning function declines. And so you have this sort of build up of these senescent cells. And again, it, it affects the space, if you imagine your body as a container for the number of fresh new immune cells that can go out and do an infection fighting. Okay. So that's why we see an uptick in things like cancer, um, susceptibility to infection or struggling to fight off infections. And then also with the rising inflammation, you have the sort of more chronic diseases like heart disease, um, you know, metabolic dysfunction, those sorts of things. So it's, it's a bit of a complex, messy picture. But then it doesn't have to be that way because you can sort of, you know, if you have a good spring, you sow the seeds, the summer everything's blooming, you have a very good harvest in those reflective autumn years, then you can go into winter prepared. And I think that's what we haven't done very well, um, because we still have this kind of evolutionary mindset where we're just kind of living the short term, um, which was what our ancestors had to do to survive. So I think winter, you can enjoy the wisdom that you've gathered. You know, you get a lot of older people who are really happy and really joyful. And, um, I think of my own grandparents who've all passed now, but I would love spending time with them. And they would tell me stories and pass on, you know, amazing pieces of information, which I think is a lovely kind of way to look at how the generations, um, mix. But if you think of like a sliding doors event, like the, the situation that our grandparents would have grown up in is going to be so different to like what our own children are growing up in now. And so if we want to set the trajectory on course, we need to kind of make sure we protect that space for children because what they're being exposed to, the way the diet has changed, like that is sort of not setting them up for success when they're going to be 70, 80, 90.

Dr Rupy: It in this winter phase, uh, is the immune system relatively static at this point? I.e. can, is there a limited amount of change that we can do in our lifestyle and diet to meaningfully, uh, impact our immune system? Or is it still relatively plastic?

Dr Jenna: Yeah, this is, I think the plasticity is definitely less. Um, there's definitely another uptick in ageing around 60 from what we know. But, um, I don't think it's, oh, you know, give up all hope. I think there's still stuff we can do, but definitely it's going to be less dynamic. It's like a car that's had a really, really long life course. It's just not going to be as efficient. You know, producing new immune cells, getting rid of those senescent cells, like all of these things are going to be a little bit more tricky. So I think it's not everything's lost, but we want to go into those years as, you know, best health as we can. And I think we should definitely, you know, you have some amazing examples of older people who are like running marathons, doing like, um, you know, amazing things in the gym. And some ways I, I wonder if things decline because we sort of let it insidiously, not necessarily that it has to be that way. Like it is harder to build and maintain muscle when you're older, but we've got these amazing examples that it can be done. Um, and is it just because it's really hard that we don't end up doing it?

Dr Rupy: Yeah. Um, let's talk about an immune health toolkit to, to sort of frame this, um, immunobiography that, which is a term that you use in your book, right? This immunobiography. Is this, is this the, the seasonality, what we've been describing thus far?

Dr Jenna: Yeah, and just how it changes across the life course and we have to kind of not think of it as one static thing, but how it changes and that we always have an opportunity to write the next chapter.

Dr Rupy: Got you. I love that. Um, so when we think about like an immune health toolkit, I immediately think of, uh, lifestyle, diet, obviously, um, the environment that we choose to live in, um, actually whether that is by choice or not. Um, and then sort of cherry on top, supplements, other practices that are perhaps outside of the norm of what we would consider, uh, lifestyle medicine. Um, where should we start?

Dr Jenna: I think I like the idea of like a pyramid where you have along the bottom is getting a diet in from the outset that's going to really support the microbiome and allow you to maybe drift off course in your 20s and 30s, but it's given you the foundation to come back to. Um, obviously we'd love everyone to be born into the world, you know, in a way that is really supportive of the microbiome. It's not always necessary and we have a lot of innovations coming through in that area of how we can help seed people with the best possible microbiome. Um, I think the, the bone health and the muscle mass, that has to be again from the outset. I think particularly in the autumn years in midlife, it's easy to get really sedentary. I know that my, uh, job, I can sit at my computer for long hours. Um, I can drive if I want to, like it's easy to let those things slide and not realize that this is where you have to really look after the muscle mass and I think that that's exercise needs to be kind of reframed in a way that we don't have to just wait until we get into the gym to do it because probably by the end of the day we've run out of motivation and mental capacity to even think about that if we've had a, you know, a lot going on. Uh, and make exercise more kind of intrinsic into our day. So we don't even have to think about it. More walking, more moving, more lifting things. So, you know, that diet pattern and the movement patterns have to be really consistent, but not perfect. They're going to be times. I think if you build consistency up enough, it's the machine is robust enough to handle, um, you know, perturbations. And I think that's something that we, we often miss. Like you're just looking for that resilience, the resilience in the microbiome that it can handle the odd time where, you know, it gets disrupted by a medication or something necessary. Um, social connection is so important. Uh, I just think that we underestimate that. We human connection can be a source of pain and suffering as much as it can be a real kind of salve and a real kind of tonic. Uh, and it's negotiating that balance all the time and realizing that however self-reliant we are, we need that connection. We need to be within communities where we feel supported. So if you imagine this base of the pyramid where we've got the diet, we've got the, the movement, we've got social connection. And then sleep and circadian alignment. I think, you know, it's really easy to become misaligned with our circadian biology just because of again, lifestyles that we live. We don't necessarily live very seasonally in the UK, you know, the sun goes down at 4:00, uh, and, um, we can only imagine what our ancestors would have done. Um, things like vitamin D, you know, that can go down in winter and that actually encourages fat storage, which would be really important to get through the winter. And then it goes up in the summer, which encourages sort of more muscle building. So there's sort of a seasonality in we would have naturally lived according to that. So that would have been quite important. But now it's a bit of a mismatch whereby we don't need to store fat for winter. Um, so kind of just remembering all of these, um, and putting that at the base of the pyramid. And then moving up, I would actually put in monitoring ourselves. So that comes from, you know, going and talking to your GP or seeing what regular blood work you might need or keeping a track of symptoms. So often the case, I'm sure you've had that particularly in general practice, people come to you, you've got no baseline to know how much they've deviated from normal, what is a genetic thing where they might have really high, you know, in one of their white blood cells, for example. Um, so getting some data and information on yourself. And I think that can, that can be a double-edged sword. There's lots of tracking things now that we can start to build up data. Um, uh, you can go and invest down that route if you want, get blood work done regularly. And having that can be quite, um, useful as a, if you want to really, you know, dial things in, you've got that layer of data. But then marrying that with your own, what we, what I call immunoception. So it's a form of interception. So what we feel from our own body. So, you know, when we feel hungry, that's a sensation that we can tell. But there's lots of different ways that we can sense what's going on in our body and kind of putting that together, that sort of somatic experience of our body and trying to figure out what that might be telling us, seeing it as information, seeing symptoms as information instead of, um, you know, a sign that your immune system's gone wrong. It's like, well, no, it's, it's doing its job, but we've created an environment where it's got confused or it's misfiring.

Dr Rupy: I, I think that intuitive sense of wellbeing is something that we are increasingly passing off to, uh, devices, experts, tests, um, and, you know, as someone who wears, uh, a sleep tracker and I do like investigations and getting my, you know, I do DEXA scans regularly, I do VO2 max, I do all the things that I think are interesting to me, but I don't, I still like lean into myself, which is why I meditate every, every morning, or wherever I can actually at the moment. But these, that for me, I think is probably the best tracker. Yeah. You know, and and everyone has access to it, but it requires that practice, that sort of sense of intuition, like whether you do feel off or not and how that's going to dictate or direct your, your day and what you're going to eat and how you're going to exercise and.

Dr Jenna: Yeah. And having that confidence in yourself. And I think it only comes from stillness, doesn't it? Because again, going back to our complicated relationship with time, we're always so busy. We always feel so time poor. We always feel like we haven't got enough time. But if we do make the time and it just has to be 10 minutes a day, we can like learn so much about ourselves. And then you're like, oh, I do feel really tired today. I didn't sleep well. I might feel compelled to make poorer choices because my blood sugar is all over the place. I might just skip the gym today because I probably just need to come home and decompress and have an early night. Like you can start to be like, oh, I've got agency, you know, because I'm listening to my body and not feel like, oh, but it's Wednesday. I always go to the gym on a Wednesday. I can't ever skip. You know, it's just be a bit more flexible and in tune. Um, and I think that can go two ways. We can be like, oh, I just want to eat the cake and do nothing. But it's knowing that that's not really right for you. Um, and that comes just, you know, with your own experience of your body. And all of the tech is a great way to kind of explore that a bit deeper, um, and a bit more empirically, but it, like you say, that intelligence that you have within is actually way more telling.

Dr Rupy: Yeah. And then above that, that's where I bring in the supplements. And it's really funny because people get very like either or about supplements. And I'm like, well, can't you just bring in what you need at different life stage? Like, you know, when your wife was pregnant, she maybe needed the prenatal supplements, um, that's recommended. But that wouldn't maybe be something that you take all the time. You know, there's different phases of life and it's to supplement what's already there. And I think that's what's sometimes we have that future discounting, like we're paying money for something, therefore it must work. So I don't need to do the other stuff, like the basics, because I'm paying for this. Like there's a weird kind of psychology there. Yeah. Um, but I think go with the stuff that has quite robust evidence that we know. And that's, you know, look after your vitamin D levels, not just from supplements, but, you know, safe time out in the sun. Um, magnesium is really coming through as being important for, um, your, uh, health and longevity. Um, omega-3s again.

Dr Jenna: Which form of magnesium? Because there's so many different forms and it's really confusing for people like, is it citrate, oxide, theonate, like.

Dr Rupy: Yeah, well, this is, um, some are cheaper, which is why they're used in supplements. Some are a little bit harsher on the gut, like citrate can be, um, can give people loose stools. Yeah. Um, I personally like glycinate or bisglycinate, which is attached to the amino acid glycine, which is really calming. It works on the GABA system. So it's, it's not, um, sedative or sleepy, but it's nice to take in the evening. And magnesium as well is that works on the nervous system helping to relax. Um, and glycine itself has actually been identified as a longevity molecule. So, um, it's an amino acid, so it's found in lots of proteins. Um, but high glycine diets are associated with, um, healthy long lifespans.

Dr Jenna: Where, where do we find glycine? Because I know it's one of the components that's, uh, in a quite a large amount in collagen. Is it proline?

Dr Rupy: Yeah, so if you have, um, 10 grams of collagen, you've probably got about seven grams of glycine in it. So we would probably got that from collagenous meats that would have been eaten traditionally or, you know, you can take it as a standalone supplement. You can take it as a magnesium glycinate, although the glycine part would be much lower. Um, or in collagen supplements as well. So things like that is really important. I think the, the prebiotic, probiotic space is kind of interesting around longevity. I think particularly things that are helping support the gut barrier and reduce inflammation. But it's, it's a messy space. Yeah, I think that's.

Dr Jenna: And when would you be thinking about taking some of these supplements? Because in my mind, if I'm 20 years old, I'm not taking any of this. I'm taking, I'm resilient. But if I reverse the clock, should I have thought about some of these things?

Dr Rupy: Yeah, well, that's, I think the million dollar question. And that's where we need these really long expensive studies, which we're not going to get. And, and that's something that's often missed in the marketing that it doesn't say like, oh, if you're 80 and you start taking this, it's going to remove your senescent cells. Like, um, I think, um, that we don't know. But I think you, you can be quite robust in the first half of life. And then maybe in the second half of life is where you want to really take care. But obviously you don't want to be going into the second half of life already with some specific deficiencies. But it's more like the kind of cherry on top longevity supplement. Maybe you want to be considering more. Okay. Um, and also, I think there's an argument for like, if you start taking, you know, something like a senolytic, which is a lot of, um, there's a lot of, uh, supplements that are marketed as, um, senolytics. So quercetin is a senolytic, so it helps, um, kill off senescent cells. Um, and there's actually been some quite decent clinical trials combining senolytics, so quercetin with dasatinib, which is a chemotherapy drug, a specific dose, if you put those two together and you do what's called a hit and run protocol. So you sort of blast people with this, and then you give them a break, and then you go in again. This kind of blast of these compounds, quercetin is a flavonoid, and it, um, helps tear up some of these senescent cells. So you're sort of have an extra pruning of these senescent cells, which is really interesting. But whether you want to be doing that in a 20 year old, because maybe the senescent cells are playing a function, they might be sort of protecting those cells from becoming cancerous. So the stage of life is something that's not quite appreciated and we don't quite understand what to do when. I think that's definitely where we need to be headed in the future. I, I certainly want to know what should I be doing now versus when I'm 60, you know, is there differences? And we don't quite know that. I think protein's a good example, or fasting is a good example actually, because we have data around how fasting might be really good for longevity. But I don't know if I want to put someone who's 70 on a fasting regime where they might lose loads of muscle mass. And actually there's a few studies that suggest that maybe that time of life isn't when you should be fasting. Maybe it should come before that. So there's a lot to be worked out there.

Dr Rupy: It's really interesting because when you were talking about quercetin and, uh, or quercetin, I always pronounce it incorrectly. I'm probably going to get corrected on YouTube, but, uh, plus dasatinib, uh, or let's say another, uh, immunosuppressant. Um, is that mimicking the impact of a 24 or 48 hour fast whereby you are clearing some of those senescent cells or upregulating the process of autophagy? Yeah. Um, and maybe that drug and supplement combination is something that you can give to a 70 year old without the, without the potential detrimental effect on loss of muscle mass.

Dr Jenna: Exactly. Yeah. And even things like, you know, really intense exercise can be a senolytic. But you might not, somebody who's in their 70s and maybe more frail, might not be able to do that without injury. So like you say, there could be applications that are adjusted and personalized depending on age and life stage.

Dr Rupy: Okay. Um, in terms of, uh, epigenetic clocks, I don't know if you, we mentioned earlier about like how your brain ages at a different rate to your pancreas or liver. Like, do you, and this is going into that sort of Brian Johnson longevity space. Do you believe in sort of those kind of investigations as potentially useful, maybe not now, but maybe in the future, or?

Dr Jenna: Yeah, I think I feel like they're all a little bit siloed and we need some really smart person or AI to, to bring it all together. Um, we just have that kind of knack in Western medicine to silo things, don't we? So it's easier to divide it all up and forget about us as a whole. And there's lots of different clocks now that you can get commercial tests for, but I think we need to see how they all work together in terms of painting that picture. Um, and I wonder sometimes if Brian Johnson spent the same amount of money that he does on himself on a clinical trial for some of these things that could help lots of people, that would be more useful.

Dr Rupy: Yeah, yeah. I, I like the end of one experiments to be honest. I think it's fascinating. And I think it's probably raised sort of the interest in the field that might actually generate some of those research dollars to the right place. But, um,

Dr Jenna: Exactly. It's like a case study that might then prompt to do a bigger, a bigger trial.

Dr Rupy: Yeah, yeah. It's really interesting watching what's going on and the interest and the number of questions that we've had about particular supplements that are in his regime. Um, so we'll do a quick fire round of supplements. I know quick fire, I say that in inverted commas. Uh, let's talk about creatine. Um, is creatine in for everyone, not just those who are looking to build muscle?

Dr Jenna: Oh, yes, definitely needs a reform and a reframe in people's minds. Um, it came from the sports and exercise field because they observed the effects on athletes. Yeah. Um, and it was safe and it wasn't considered a performance enhancing drug. So suddenly, you know, all athletes are getting on it. Um, but it helps with, um, the energetic capacity of a cell essentially, to to put it really like mildly. Um, and obviously muscles when you're exercising, they need to be able to regenerate ATP, the energy currency really quickly. But also, um, there's lots of other energetically, you know, um, active cells in the body, the brain, for example, the immune system, you know, these need a lot of energy. And so what's come out in the wash because it's such a well-studied supplement is that, um, creatine has some really amazing benefits for the immune system and also for cognition and brain health. Wow. And so I think that, you know, if, if you're an omnivore, you're probably sitting at around what we call 70% saturated. So you've got about a 30% um, opportunity to improve your creatine stores. Um, if you're a vegetarian or vegan, you're probably sit a bit lower than that. And women tend to have less creatine stored than a man. So women have sort of more to, um, gain from supplementing. Personally, I didn't take creatine for years because I kind of had it in my mind that it was that 1980s gym bro bodybuilding thing. Um, and then when I started looking into it, I was like, oh, I'm going to give this a try. My God, I really recognized an improvement in exercise capacity within a few weeks. Um, and then sort of the broader benefits around cognition and just feeling, I feel very like, um, yeah, aware and alert and like definitely an improvement. And I think it's one to, to trial. It's very safe. It's relatively cheap, um, compared to some of the supplements. It doesn't taste of anything. 3 grams is sort of the minimum to get the effects and you'd start to see benefits after two weeks. But some of the studies on cognitive health are going up to like 20 grams.

Dr Rupy: 20 grams.

Dr Jenna: Um, because I think that the brain seems to respond to these higher doses. Um, but yeah, with very minimal side effects. Some people find it upsets their gut, but take it with food and just increase the dose very slowly.

Dr Rupy: So yeah, very pro creatine.

Dr Jenna: Very pro creatine. I can tell. So, um, with the, with menopause and perimenopause and postmenopause, are there any studies looking at creatine and potentially helping the common symptoms of brain fog and fatigue and like energy?

Dr Rupy: Yes, this is all coming out now. I've read there's a, there's a really nice review about women across the life course and creatine. And a few on things like bone density as well, which is really interesting. So I think, um, it's definitely one that I would encourage people to be a bit exploratory with, try it out. As I said, it's not too expensive as well, relatively to some of the supplements.

Dr Jenna: Interesting. Okay. And I wonder if these have potentially preventative effects on cognitive decline as well, you know, when taken over time. And I guess because these supplements have been out for so long, maybe this is like one that could be used in clinical trials and taken over time.

Dr Rupy: Yeah, exactly.

Dr Jenna: Because it's, it's safe to look.

Dr Rupy: Yeah. That's really interesting. Okay. Taurine, one to watch. Um, let's talk about, let's, actually, no, there's a couple of things. Peptides. So peptides, short chains of proteins, um, getting a lot of attention at the moment, injectables, peptides in skincare. What's your take on those?

Dr Jenna: Yeah, it's funny to call them peptides, isn't it? Because to me, peptides are the, the umbrella term for short chains of amino acids.

Dr Rupy: Yeah, yeah, yeah.

Dr Jenna: Um, but I think that, um, it's a very interesting space. I'm kind of like watching and waiting. I think, um, it just reinforces to me that protein is more than just these amino acid building blocks. So a lot of the time we talk about protein as being one thing and it's made up of these building blocks. But when you create little peptide chains from unique, you know, Lego bricks, as it were, they have this amazing signaling function in the body, which we can then create different peptides for different jobs. And I think it's going to be a real interesting space to see what comes.

Dr Rupy: Yeah, yeah. I, I mean, like, I've talked about it in my book as well. We don't appreciate that a lot of our hormones are basically peptides. They're just strings of amino acids. You think about insulin, for example. I mean, there are steroid hormones, which is different, but, you know, that it's just, they're just hormones, strings of, of proteins that have these signaling functions. So I guess, yeah, I agree. I think it's one of those that's one to watch, but it is quite funny to see people injecting already and, you know.

Dr Jenna: Again, I like observing people doing their own end of one experiment and then sort of like watching the literature evolve, but yeah, I'm not quite ready to dive in on myself.

Dr Rupy: Yeah, yeah. Uh, okay, and collagen. Now, I've thought collagen has been BS for a long time. I want you, I want you to convince me that collagen is something worth investing in potentially.

Dr Jenna: Well, collagen is, as I said, it's, it's one of the, um, most, it's the biggest protein in the body and it's the glue that's sticking things together. So we, the reason, one of the reasons I think it's quite heavily poo-pooed is because it's marketed to women as an anti-ageing thing. Or people in the sort of sports and exercise field will say, well, it's an incomplete protein. So it doesn't have the full composite of amino, of essential amino acids. It's not high in leucine like things like whey. So in their mind, it's kind of like, well, there's no point taking that after a workout because it's not going to help with the muscle protein synthesis. And I think, well, not all proteins are there for the same job. Not all proteins need to be for muscle protein synthesis. Like different proteins, different jobs. Um, and the other thing is that, you know, our collagen levels do decline with age. And women in particular after menopause, they see a really sudden decline. And women will often report like joint issues, stiffness, pain, and, and just the kind of structure of their, their body, their, you know, face is obviously one area that people will notice, um, because the, um, fibroblasts that are producing collagen are stimulated by estrogen. And so when the estrogen is no longer there, that signal is gone. Um, so you get a even bigger decrease in collagen levels in the body after menopause. And so, I guess the thinking followed that if you take collagen supplements, you're replacing what's lost. But people would say, oh, but the collagen's just being broken down into amino acids. Can't I just get that from other proteins in my diet?

Dr Rupy: This is my thinking.

Dr Jenna: Yeah, so yes, you can. Collagen has a quite a unique amino acid structure. So it will have amino acids that are, are rarer in other foods. So again, thinking about all those different levels of amino acids, collagen's providing something that, you know, other proteins might not get. So, but then there's also these peptides within the collagen. So it's, it's hydrolyzed as part of the production process, which makes little short peptide chains. And there are studies showing that these do cross the small intestine during digestion and they go to certain parts of the body and they act as a signaling molecule. So if you have these di and tripeptides, they're signaling that the body needs to produce more collagen. It's almost like, oh, look, the collagen's being broken down because we've got these peptides, we need to produce more. So this has been demonstrated in the literature. Um, and it's thought to be one of the mechanisms by which supplementation works, as well as providing a pool of these really unique amino acids that make up collagen that you might not get from other dietary proteins. So it's, and there's maybe other mechanisms we don't know yet. Um, but I was recently involved in a clinical trial. The studies are not published yet, so I'm still writing the manuscript. Okay, yeah, yeah, yeah. Um, but we looked not only in the skin, but of the whole body. And, um, because I think that's where the message gets lost is when we start marketing things to women, people go, oh, well, you know, it's not as good as retinols for anti-ageing. Well, it doesn't have to be. It's a, it's a dietary intervention. It's a food. It's not even sold as a supplement. It's, it's essentially a food. Um, but the collagen fragmentation within the skin structure, and that's on the face and on the body, um, was reduced. So the collagen breakdown was reducing. That was over 12 weeks. Oh, interesting. Um, and then the hydration of the skin, like the structure of the, the skin, um, was improved, but we also saw improvements in things like gut health because the whole structure of the gut is made of collagen.

Dr Rupy: Oh, really? I didn't think I appreciate that.

Dr Jenna: Yeah, so it's, it's basically the scaffolding that's, you know, holding it together. And going back to our conversation about the gut integrity, like that barrier being really important. Um, so then we looked at, you know, energy levels and exercise and pain and all these different aspects that all showed improvements. So I think we need to stop thinking about it as a beauty supplement and we need to think about it as a food, um, and think about the sort of unique mechanism of action and that we're not taking it for muscle protein synthesis. It's got a different function in the body. And then, uh, people always say, oh, but, you know, um, there's many other things people can be doing, like diet and exercise. And I'm like, yeah, I'm not ever telling people to take collagen supplements. I'm not here suggesting you have to buy it. I'm kind of laying out what I've learned. Sure. And I always go into a space quite skeptical and I want to understand it all before I'm able to sort of make a decision of whether I want to take something or not. And so, you know, if I can lay out information, people can decide because there's a financial cost if that's what you want to do. Um, and it doesn't have to be collagen or other things, you know, like dermatological treatments that do have anti-ageing effects. You can do both. You know, that's, um, it's not a one or the other.

Dr Rupy: Yeah, yeah. No, I agree. I, you, you've convinced me to relook at the literature for sure. I, one of the things that I've always had, uh, is when I look at some of these studies where they give people collagen, they look at subjective measures of skin hydration and wrinkles and all that kind of stuff. And what I want is an objective measure where they do a skin biopsy and they can actually see that as a result of said intervention, there is a significant improvement in the structure or hydration, whatever it might be, is an endpoint. And that for me has been lacking.

Dr Jenna: Yeah. So we did do those objective measures because, yeah, the subjectiveness can be problematic. But also just speaking to people in the sports and exercise field, like there's studies now on, um, female footballers and injury, um, reduction because all the, the, the ligaments and tendons, uh, of the joints, as well as the bones and muscles, you know, those are all made from collagen. That's part of the scaffolding. So looking at seeing, you know, female footballers are more prone to certain injuries. Can we use collagen supplements as a way to offset that? So I think if you go into certain fields like, like sports and exercise, um, physiology, then you're like, oh, this has been taken seriously as an intervention. It's just when you go to like the sort of female space and beauty, I think that that's when people like to not take it seriously.

Dr Rupy: Is there a particular type of collagen if people are interested in collagen that we should be leaning into more? Because from my reading, like there's tens of different types of collagen, right?

Dr Jenna: Yeah, there's 20 odd different types. Um, the predominant one in the body is type one. Um, most of the supplements you'll see on the market will be type one. And they're what we call hydrolyzed to make these little peptide chains. So this process is quite important to make these peptides. And then I think just look at sourcing. So, you know, it's a byproduct of the meat industry. So you want to think about what, you know, the supply chain, where those animals have come from. Um, I know that South American sourced collagen has been linked to deforestation. So think about the provenance. Some people will add in lots of fancy ingredients, but I think if you're getting a good diet, so vitamin C is really important for collagen synthesis. You don't necessarily have to have that as a supplement if you're getting plenty from your diet. So it's, um, uh, and it's very heat stable. You can put it into food. You can put it into your soup or, you know, a stew. It's also a source of protein. So you're adding protein to that meal as well.

Dr Rupy: Yeah, yeah. Jenna, this has been awesome. Uh, I could talk to you for so much longer. I've got so many more questions, but I think we'll call it there. But I, I just think that the one thing I'm going to take away from this conversation is this, this parallel with the seasons and like where we are with the different seasons and this, the importance of the soulspan. Like the soulspan is a really beautiful concept, you know. I think about lifespan and healthspan, obviously with my medical hat on, but I don't think we lean as much as we should be into the, the soulspan. And I think that's something that you articulate so well when we talk, but also in, in your books as well. So, yeah.

Dr Jenna: I really appreciate you.

Dr Rupy: Oh, thanks for having me.

Dr Jenna: And sorry for my sunglasses.

Dr Rupy: I love it.