How to Eat for Gut Health & Longevity | Lifespan with Dr. David Sinclair - S2, Ep. 8

0:00Dr. David Sinclair:If you eat a lot of sugar, you will have a faster aging process than if you don't. The body's turning on itself. When there's a lack of inflammation, other aspects of your body come back to life. Our bodies start to have a harder time as we age in recognizing what nutrients are and how to use them. Your microbiome, which is the bacteria and the fungi in your gut, actually control your health and your longevity. You've bought yourself a little more good life. Welcome to Lifespan, a show where we discuss the cutting-edge science of aging and how to live healthier at any stage of life. I'm David Sinclair, a scientist and professor working on understanding why we age and discovering new ways to slow and even reverse the aging process.

0:52Dr. David Sinclair:On this show, I share an insider's look at the latest from my lab, the field, and what's just around the corner.

1:06Dr. David Sinclair:Hey everyone, welcome back to The Lifespan Show. I'm here again with Dr. Matthew LaPlante, my buddy and co-author. If you caught the first episode of this series on the hallmarks of aging, we talked a lot about mitochondria, what goes wrong with them, and why that can leave us with less energy as we get older. And also how things like exercise and cold exposure can reinvigorate them. This is part two of three, and today we're going to talk about food, because what you eat dramatically affects both the signals your cells receive and the microbial community living in your gut. But don't worry if you didn't catch the first episode, you can always go back.

1:40Dr. David Sinclair:You don't need to watch these in order. What I'll also talk about today is what you eat can also affect the proteins in your body. Too much sugar or carbs that turn into glucose in the bloodstream can attach to proteins in a process called glycation. We can actually measure that attachment using a surrogate for the other proteins in the body called HbA1c. This is sugar attached or glucose attached to hemoglobin. It's a test many of you have probably already had. And today you'll hear about inflammation, sugar, your gut, and something called nutrient sensing, which is how your cells know whether nutrients are abundant or scarce, and why that matters if you are to live a very long time.

2:18Dr. David Sinclair:I'm so excited to share that Lifespan magazine is now available, along with everything we're building around it to help you live a longer, healthier life. You'll get the gorgeous 100-page magazine, early access to Lifespan episodes, my longevity newsletter, clinical trial updates, AMAs, exclusive interviews, and a lot more to come. Go to Lifespan.com to read the magazine, see what we're building, and support medical research too. There's a free version, an$8 a month membership, and a founder membership with lifetime access to the magazine, bonus material, and some personal gifts from me. Life's too short.

2:58Dr. David Sinclair:Let's change that together. Okay, let's go. So let's start with chronic inflammation, something that a lot of people experience and that there's actually quite a bit that we can do about, but let's start with what is chronic inflammation? Well, inflammation is a state that is very helpful when you need to fight infections. We need to be able to detect things that invade us, want to eat us, want to feed off us. And we've got an immune system to address that. The problem is that as we get older, our immune system becomes weaker at addressing and attacking invaders, and it turns on ourselves. And that's called chronic inflammation or inflammaging.

3:40Dr. David Sinclair:And this is a process that is a problem because it erodes joints. It causes cells to accelerate in their aging. And also we get diseases like diabetes, heart disease, even Alzheimer's have a large component that is accelerated, made worse by this inflammatory process that we all get as we get older. There are ways, of course, we now know that you can slow that process down and even reverse it. How do we know that we have chronic inflammation? I mean, there are tests for inflammation, but there are other just symptoms of inflammation that people experience as they're getting older. So there are lots of ways to know if you're getting inflammation.

4:18Dr. David Sinclair:Of course, the most accurate way is to do a blood test and look for markers like C-reactive protein, which is a marker for cardiovascular inflammation, IL-6, IL-1 beta, TNF alpha. Your doctor can test for those, or you can order a kit online typically. But if you just want to know daily how you're doing as a human being, the kind of symptoms that you might see would be your skin might feel inflamed. So you're getting itchy, redness. Your eyes might look inflamed. Your joints might start to feel a little bit stiff or even painful. Arthritis being the major downstream effect of that. That's what's really going on is that your body's turning on itself and you're not feeling great.

4:57Dr. David Sinclair:And eventually, if you don't slow it down or stop it, these effects of being lethargic and your joints hurting will actually become diseases. Inflammation is something that we can do something about pretty easily. Oh, for sure. Now, just keep in mind that even if you address inflammation, you're not going to stop aging. But let's start with the easy stuff. So inflammation, very easy. What you can do is change your diet. There are low inflammatory diets. It's the one that I've been on now for two years. It's a fairly unusual diet. It's a vegan diet. I was turned on to it by looking at the amazing health of my partner, Serena Poon.

5:36Dr. David Sinclair:She looks a lot younger and feels a lot younger than she is. I switched. Actually, she came to my kitchen and threw out half my food, but I was inspired to switch into a low-inflammation diet. What is that? Well, it's stopping alcohol, which I know you've done too for many years now. Yeah, I beat you to that one. You did. So you inspired me too. I thought if Matt can do it, anyone can do it. That's true. If I can do it, anyone can do it. Right. Yeah. And that's true for the both of us. We are pretty hedonistic and lazy, I would say. And if anyone sees or hears us do something, it's like, you can do it too.

6:07Dr. David Sinclair:So that's alcohol off the table for us. My mind is so much better. I can remember things. Actually, I can remember your name now. That's great. I'm glad. We were talking about this over dinner a couple of nights ago about how we feel like we might have wasted a whole bunch of years with all that alcohol. Oh, definitely. The other thing that I changed was I got off dairy and it's surprising how quick the effects are. When I got off dairy and I was eating cheese every night, so stop that. My inflammatory markers, which I mentioned, those things you can measure in blood within two months had dropped dramatically.

6:42Dr. David Sinclair:And remember, I was not an unhealthy person at that point. Oh, I saw your blood work. It was great. I thought I was the healthiest I could possibly be, but this got me to another level. I went back, at least based on some blood tests, a number of years, even younger than I was then. So, I mean, now I'm at least a decade younger, at least based on those tests. So no dairy. And then I rarely eat meat. I'm not really a vegan. I'm a struggling vegan, but I rarely eat meat. And a lot of people say to me, how do you do that? Well, it's helpful if your partner is a chef and a vegan as well, but I no longer crave meat.

7:18Dr. David Sinclair:I used to be one of these people that if I had dinner, there'd be a steak or a piece of fish and then some other green stuff that I didn't really want to eat, but I just ate it for vitamins. I'm off that. And actually, because I feel so good now and other people say, wow, you look better, your skin's better, I'm sticking with it. It's not difficult once you make a lifestyle choice like that. But that doesn't mean everyone should go vegan. I know people love meat, but I would say try to be more focused on plants if you can. Choose dishes that are not just meat and a little bit of veggies on the side most days of the week.

7:53Dr. David Sinclair:And you'll find that you'll feel better. Your inflammation will come down. That's a fact. That's not really speculation. One of the things you haven't mentioned yet is sugar and its relationship to inflammation. Yeah, well, that's so obvious I forget to mention it. Just sugar. Think of it as poison. It's okay to eat a dessert. Occasionally, I eat a dessert. I typically just steal it from people, just taste it. But if you're drinking sodas with sugar, pure sugar in them, or just daily life, you know, you've got sauces and stuff that's in coffees, these fancy coffees. It's amazing how much sugar is just in stuff that you don't even think, with ketchup.

8:30It's tens of grams in these products. There's one bottle of sugar-free ketchup at the store and 47 bottles of stuff that's got high fructose corn syrup in it. Yeah.

8:39Dr. David Sinclair:So think of it this way. This is what helps me is that So sugar tastes good, of course, and it's good for your energy. Your brain needs it. Your muscles, in fact, need it even more. What sugar does to you, in part, is it actually sticks to your proteins. It's called glycation. Glycation is modifying proteins so that they don't work. And this is a process of aging. One of the measures of glycation that doctors use is called HbA1c, which is glycation of hemoglobin. And that's a good measure of how high your blood sugar has been over the last two to three months. and if you eat a lot of sugar then you'll have high levels of sugar attached to these proteins and it's not just hemoglobin that gets attached to sugar all proteins pretty much all proteins in your body get caramelized or caramelized if you're australian or canadian this is a process that is toxic so if you have low carb low sugar diets your proteins will be pristine more pristine they won't become dysfunctional and you won't be so predisposed to the diseases of aging that come much later it's actually known that if you eat a lot of sugar you will have a faster aging process than if you don't the sugar itself will attach to proteins and modify them glycation and the ultimate product of that are called advanced glycation end product these are molecules that are attached to the proteins that cause them to behave badly.

10:03Dr. David Sinclair:But what's often forgotten about is that these glycation products are happening to pretty much every protein in every cell. And what we're looking for is an ability to slow that down or even reverse it. The problem with that is that there really isn't a way that the body has to get rid of these sugar caramelized proteins, except to recycle them completely. But it would be really exciting if we could have a molecule you could ingest it and clean up those proteins. Anytime you say the words, it would be really excited if we had, I think there's somebody in your lab who's working on this or one of your companies is working on this right now.

10:39Dr. David Sinclair:Well, in this case, we have some ideas. We haven't started, but there are other labs. There was a paper that was published that catechins, one of these plant molecules, you can find it in green tea, especially matcha as well as chocolate, that these catechins stimulate the ability of the body to get rid of these modifications on the protein so you can reduce your glycated hemoglobin. And there's another thing that's really interesting. Albumin gets modified by sugar as well, gets glycated. And I was looking it up recently, glycated albumin is toxic to human cells. And it could be, though not proven, but we're going to investigate this, that the sugar that's attached to albumin in your body is toxic.

11:20Dr. David Sinclair:And it might be why when you have blood transfusions or what's called plasmapheresis, where you replace the albumin component of your blood, why that's so healthy. Because it's not glycated. It's fresh. It's fresh. Yeah. Fresh blood. Exactly. One thing that's important to me is that Lifespan only partners with companies that I genuinely believe in. They must be grounded in science and willing to support medical research that will ultimately change how we treat aging and diseases. Their support also helps keep this podcast free for millions of listeners around the world, which brings me to a science-based wearable that I'm particularly fond of, partly because of its scientific foundation at Harvard, where I work, but also the founder's own research and scientific rigor.

12:05Dr. David Sinclair:Of course, I'm talking about the Whoop band, the one that I rarely take off. As a scientist, I like measuring things rather than guessing, and Whoop continuously tracks my sleep, my resting heart rate, my heart rate variability, respiratory rate, daily strain and recovery, and other aspects of my health, giving me objective data about how my body is responding to the changes that I make. On weekends, you'll usually find me on Cape Cod, in my workshop or outside on the property, planting fruit trees, repairing the house, or hauling lumber in my old 1992 Ford F-150 pickup. Sometimes, however, I wake up eager to get outside, but my whoop tells me a different story.

12:44Dr. David Sinclair:My heart rate variability is lower than usual, my resting heart rate is elevated, and my recovery score is really poor. So on those days, I still head out, but I pace myself. I found that listening to those signals helps me recover better and work harder over the long term. I appreciate that WHOOP is backed by great science. For example, in 2022, Miller and colleagues published a study in the journal Sensors comparing six leading wearable devices against clinical grade measurements of sleep, heart rate, and heart rate variability. WHOOP was among the most accurate for measuring overnight heart rate and HRV.

13:19Dr. David Sinclair:These are the two biomarkers that I pay close attention to because they provide valuable insights into recovery and physiological resilience. So if you don't already use WHOOP, I really encourage you to give them a try. So visit join.whoop.com slash lifespan, and you can use the code LIFESPAN to receive your free whoop and your first month of membership. Okay, so diet is one of the easiest ways to impact inflammation. I don't want that to come across as thinking like changing your diet is really easy. I know for a lot of people it's hard for us. It's been hard as we've gone on that journey, but that's sort of the most straightforward way, the most accessible way to impact inflammation, but there are other ways.

14:04Dr. David Sinclair:Oh, for sure. What you're doing with your diet is you're ingesting anti-inflammatory molecules from plants. Typically, they're made by plants, not by animals. And that's why this diet works. You can also take molecules that are purified from plants as supplements, such as curcumin and catechins, which you can find in a whole variety of foods as well as supplements. Risveratrol is one that we've worked on in my lab, which is a polyphenol, a chemical that's found in grapes, and you can take that as a supplement. These are all molecules that are highly anti-inflammatory that I aim to get both from my diet, but also I take them as supplements every day.

14:40Dr. David Sinclair:But for now, let's go on to some of the other tertiary causes of aging, see what we can uncover here. Okay. Dysbiosis, that's imbalance in the gut microbial community that is very associated with disease. Did I get that right? Is that? It is. I love that it's a community. We always want to foster the community. What was realized just about 20 years ago from a friend of mine, Jeff Gordon, and his team was that your microbiome, which is the bacteria and the fungi in your gut, actually control your health and your longevity, we now know. And as we get older, that community changes. We see shifts in the types of bacteria that are in our gut, and they become less conducive to health.

15:21And they become less diverse.

15:23Dr. David Sinclair:They do. Which is, I think a lot of people think, oh, like more bacteria is bad. Lots of different kinds of bacteria is bad. No, actually in our gut, lots of different kinds of bacteria is best. And we start to get types of bacteria that cause inflammation, which as we mentioned is terrible, but that we also start to lose bacteria that make molecules that make us healthy. So there are short chain fatty acids, short chain fatty acids. We can either take as a supplement, butyrate is one among others, but also these bacteria make them naturally. And we start to lose those species as we get older.

15:53Dr. David Sinclair:So what do we want to do? We want to maintain those communities by having a healthy diet, but we can also take these bugs with a pill. And so probiotics, which are enhanced by prebiotics, prebiotics are the food for those bacteria, to get back the more youthful communities that we might have lost over time or by being given antibiotics by our physicians. And let's give some examples of the probiotics and prebiotics that people can take to help these communities grow. Well, the main one are lactobacilli. Those are in most probiotics, but there are other species as well that are really found in people that are super healthy athletes, people who eat vegetarian diets.

16:34Dr. David Sinclair:These are bacteria that you find in yogurt. These are lactobacilli, and that's pretty common. And good. All good. And in fact, you can eat yogurt and fermented foods that can help with your gut. But the more advanced developments in what science is saying is that there are certain bacteria that make these short-chain fatty acids specifically if you're healthy. And you lose these as you get older or if you have a bad diet. And when you eat certain probiotic strains in food or as a supplement, they will populate your gut. And instead of you having to eat these short-chain fatty acids or SCFAs, like acetate and butyrate, which often can taste terrible, your bacteria in your gut will actually make them for you.

17:17So let's go back just for a moment here because you said something and I want to make sure it's clarified here. You talked about yogurt as a good source for probiotics, but also getting off of dairy is good. I peeked in your refrigerator. There is yogurt in there, but it's a certain kind of yogurt.

17:32Dr. David Sinclair:Correct. This yogurt in my fridge is coconut based. So that also has the bacteria in it, the same as these other dairy based yogurts such as Greek yogurt. but I also get the benefit without having the inflammation. I snuck one of those the other day, by the way. What did you think? It was really good. Yeah, I mean, they're just as good as dairy, which is what I love about this diet that I'm on, which is this new lifestyle, which is I don't feel like I'm missing out at all. Let's talk now about another driver, deregulated nutrient sensing. This means our bodies start to have a harder time as we age in recognizing what nutrients are and how to use them, right?

18:15Right.

18:16Dr. David Sinclair:And that's key because we know that when the body senses that there's a lack of nutrients or a lack of energy, it responds in a positive way to enhance longevity. And as we get older, we lose that ability. And if we don't have that ability, that's messed up. In reality, when we are fasting and even exercising, our bodies don't recognize that. the way it should, and we don't get the benefits. So our job really, as individuals here, is to reignite, reinstall the ability of the body to recognize when we're eating and living well, and we'll reap the benefit that way. The kind of nutrients we're talking about are amino acid levels, phytochemicals, so from plants, and sugar is a big one.

18:59Dr. David Sinclair:Sugar is a main source of energy. The way we sense nutrients determines our longevity. It's one of the reasons why, if you eat well and you don't overeat, you actually reap these health benefits because there are some main senses in the body that measure how much protein and sugar and fats are coming in. And depending on how well we recognize those things determines how long we live. You said sugar, the most common form of this, the one everybody knows is type 2 diabetes, where the body loses its ability to recognize sugar for what it actually is. Yeah. And what we end up having is that the body doesn't recognize insulin, which is one of these hormones that tells the whole body, now you've just had a meal.

19:40Dr. David Sinclair:And without insulin, or at least the ability to sense insulin, our muscles and our brain don't suck glucose out of the bloodstream. And instead, you get a buildup of sugar, which is toxic. Diabetes is caused in part by dysfunction in a couple of the three main nutrient sensing groups. We've written a lot about this, but just to get people sort of back up to speed on that. So there are three main nutrient sensors in the body that are relevant to longevity. There's mTOR, which recognizes the amount of amino acids in your body that you're mostly bringing in from protein. Then there's AMPK, which measures energy and controls mitochondrial function.

20:19Dr. David Sinclair:And then there's the sirtuins, which respond to a lot of different things, temperature, exercise, and nutrients that are coming in. and these three main nutrient sensing groups, they attenuate over time while we age. They're not as effective. Right. So we lose the ability to sense. So for example, glucose and sugar that we're eating, our bodies don't sense that. As a result, blood sugar levels rise in the body and you get what we call type 2 diabetes. Is there anything we can do to reestablish the presence of these nutrient sensing groups in our bodies in a healthy way? Yeah, sure. In the case of inability to sense sugar, for example, we know that if you live well, so if you exercise, if you eat well and you don't eat too much, or you take certain drugs and molecules, you can reestablish the ability to sense sugar.

21:11Dr. David Sinclair:Case in point, you can take the drug metformin, you can go running, do exercise, or you can just eat less often. These are all helpful to reestablish your body's ability to sense sugar. But once our nutrient sensing mechanisms have become deregulated, it does get harder to get it back. It's true. You want to make sure that you're doing the right things from an early age in your 20s and 30s. And certainly by the time you're my age in your 50s, you want to be doing the right thing. So that's doing a lot of exercise, eating the right things, eating less often, don't become obese. Otherwise, it becomes just too hard to reverse.

21:45And those are the things that can set off nutrient sensing and put them off course. It becomes harder to recover.

21:51Dr. David Sinclair:Yeah, exactly. It's never really too late, but I think that if you're 80 and you're obese and you've got type 2 diabetes, it's a lot harder than if you start working on it in your 30s, 40s, and 50s. This is a theme here, right? I mean, once our stem cells become exhausted, once our intercellular communication becomes interrupted, once our mitochondria become dysfunctional, once that happens, it is harder. So this is this whole, let's stay as healthy as possible. Let's stay as biologically young as possible for as long as possible so that we don't have to worry about these things that are further upstream.

22:28Dr. David Sinclair:Right. Well, until we've figured out the information theory of aging and can reset the body, we've got to delay the process. And the best way to do that is to live well. But there are also molecules that we can take to reestablish the ability of the body to sense what's coming in. For example, metformin enhances mitochondrial activity. It enhances insulin sensitivity, so your body can sense the sugar in the bloodstream, and that can reverse some aspects of aging, including type 2 diabetes. And metformin has been shown in various studies to act on all three of these pathways, mTOR, AMPK, and CERT.

23:02Dr. David Sinclair:Well, that's the nice thing about this aspect is that if you address one of these pathways, so let's take mTOR, if you make sure mTOR is healthy, your other two will be healthy. Same for AMPK, it affects the other two. Sirtuins, which I work on, very similar. If you can boost the sirtuin activity, either through exercise, fasting, or small molecules, which we're developing, resveratrol was the first example, there are some better ones now, NAD boosters, which we've talked about, is another class. That will also improve mTOR signaling and also boost AMPK as well. So it's not that hard once you know what you're doing to be able to keep the nutrient sensing part of your body youthful.