329: How to Slow Aging, Fight Inflammation, & Improve Cellular Signaling With Brian Dixon

329: How to Slow Aging, Fight Inflammation, & Improve Cellular Signaling With Brian Dixon

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This podcast is brought to you by Four Sigmatic… a company I've loved for years for their superfood mushroom based products. They use mushrooms like lions mane, chaga, cordyceps and reishi in delicious products. Did you know that mushrooms are more genetically similar to humans than plants are? And that they breathe oxygen and exhale CO2 just like we do but mushrooms spores can survive the vacuum and radiation of space. These amazing fungi are always a part of my daily routine in some way, usually with Lion's Mane Coffee or Matcha in the morning, Plant protein and mushroom elixirs like chaga and cordyceps during the day and reishi at night to wind down. As a listener of this podcast, you can save on all Four Sigmatic products. Go to foursigmatic.com/wellnessmama and the code wellnessmama gives 15% off

This podcast is brought to you by Wellnesse, a new company I co-founded to bring the best personal care products from my family to yours. Our whitening toothpaste is based on my DIY formula that I have been making and perfecting for over a decade. Now, after almost 100 rounds of tweaking the formula and thousands of positive reviews, I could not be more proud to share this with your family. Have you ever read a tube of normal toothpaste? I did when my older kids were little, and I found a warning that said, "Warning, keep away from children. Do not swallow. If ingested contact Poison Control or seek medical attention immediately." That seemed a little extreme for something that I was putting in my mouth and my children's mouth multiple times a day. And I didn't want my kids using something that often that I would need to call a poison control center if they accidentally swallowed. I set out to create a truly safe and effective alternative. And the Wellnesse Whitening toothpaste is just that. It's designed to support the oral microbiome and the natural process of saliva and teeth so that teeth can stay white and strong. This dentist approved formula is safe for the whole family and will leave your teeth shiny and your breath fresh. You can check out our toothpaste and our completely natural hair food hair care products at wellnesse.com. An insider tip, if you grab an essentials bundle or try autoship, you will lock in a discount so that you can try everything at a great price.

Katie: Hello, and welcome to the Wellness Mama Podcast. I'm Katie from wellnessmama.com, and this episode is all about how we can slow the aging process, fight inflammation and improve cellular signaling. I'm here with Brian Dixon who is a Ph.D. in molecular and cellular biology from Oregon State University and is affiliated with the Linus Pauling Institute where his research focused on the underlying biochemical and cellular mechanisms of aging. And this is an area I've been fascinated with since I had to do a final project on some of these things and work with the Linus Pauling Institute when I was younger as well. He and his work have been featured on, among others, "The Dr. Oz Show". And he's authored a number of scientific peer-reviewed manuscripts on topics such as cancer, antioxidants, cellular signaling, gene regulation, stress coping mechanisms, Nrf2, weight management, sports nutrition and recovery.

Dr. Dixon has also published research in the role of nutrition in recovery from surgery, how we can facilitate a healthy inflammation response, ways to support the immune system, the aging process and how various nutrients come into play with all of those. He has worked in the nutritional industry for over 10 years, and he has seven patents related to different supplements and things within the industry. And in this episode, we go deep on the science of aging, ways we can mitigate it and things like sulforaphane, Nrf2 sirtuins, and many others. If those are new to you, stay tuned and buckle up. This is a fascinating episode.

Brian, welcome. Thank you for being here.

Dr. Dixon: Thank you so much for having me.

Katie: Well, I know you've done a lot of research in a lot of different areas, including one that is of increasing importance to me every year that goes by, which is aging. And, unfortunately, it's something I don't think we can fully escape, but I know it is something that we can mitigate and do very gracefully in a lot of cases. And there are things that we can do on a cellular level as we age to help protect our bodies. So I'd love to start with aging as a broad topic and then go deeper on some tangents from there. So let's talk about aging, in general. What factors come into play when we think about aging, both on a cellular level and then also, aesthetically?

Dr. Dixon: Yeah, well, you're absolutely right. You know, we can't stop time. That's that thing that's just constantly ticking along. It'd be nice if we could stop time or even turn it back, but yeah, it's kind of our destiny. You know, maybe to take a step back and maybe we'll start with the bad news first, and then we'll get into the good news of what people can do. There are currently over 300 different theories of aging. I mean, if you can believe that. So, people, you know, literally, since the beginning of time, have been interested in what we could do to stop the aging process.

I mean, that's that whole sort of folklore around the fountain of youth. And Ponce de León coming to North America, heading to Florida, and looking for a physical fountain of youth with the notion that you could drink this water and basically, live forever. When we come into scientific circles, scientists have been studying this, you know, for hundreds of years. But it really caught a lot of attention in 1954 when an individual named Denham Harman first proposed the oxidative stress theory of aging. That's really where a lot of aging research is focused. But I like to kind of lump those 300 theories of aging into just about five general categories.

And I think it's interesting that we can get people thinking about these different categories, because I don't doubt for a second that they're all contributing. And so if we can think about these five individually, and what we can do to kind of check the boxes, you're really gonna set yourself up for optimal health, and then possibly even extending more years to your lives. So those five general categories, I like to lump those 300 theories of aging in are, you know, very technically, we can talk about biochemical molecular and cellular theories of aging. So basically our biochemistry, our metabolism is just changing on that cellular level, and no one really knows why.

There's also some really depressing theories of aging out there that's called the programmed theories of aging. And that notion is, is that in our genes, right, in our DNA, we are literally programmed to die. So you think to yourself, "Well, gosh, why would we be programmed to die?" But if we look at other organisms around us out in nature, you know, it's really every organism's job on this planet to reproduce. And so once we've passed on our DNA to that next generation, there really is no true biological reason to keep us around. In fact, an organism gets past its reproductive years, all that individual or organism is doing is just consuming resources.

That doesn't apply so much to humans. You know, we have that knowledge base that comes with age. And in fact, there's a few higher mammals on this planet where it is evolutionarily beneficial to keep the elderly around. So obviously, humans is one great example. So think about all those things that we learned from our grandma and our grandpa. Whales, they keep the elderly around. In fact, it's usually the grandmother orca whale that's raising the young. The elephants are also one long-lived species where the oldest elephants are playing a huge role in their family circles. So programmed theories of aging, that's number two. Then we can get into number three, the cycle social theories of aging. So basically, what that means is we just need to keep our minds sharp as we age.

A lot of individuals as we get older, we tend to isolate ourselves. We tend not to spend as much time with family and friends, and it really leads to that kind of rotting away of our brains. Number four, I put in a loss of cellular communication, and I throw that into the mix. So what does that mean? Well, basically, our cells, organs, and tissues just aren't talking to each other as well as they used to. So think about hormonal changes occurring as we get older. So, you know, in men, testosterone levels can decline. Women when they hit menopause, I mean, their hormones are going all over the place until they can find that new normal … so hormonal signaling isn't working as well as we age. And then just our ability to adapt and respond to our environment.

So if we're exposed to, let's say, environmental toxins or oxidative stress, we have these built-in systems to be able to deal with those stresses. But they're just not sensing the signal and then communicating the potential trouble to the rest of the cell or even the other tissues and organs in our bodies. And then lastly is the damaged theories of aging. So just the different biological structures inside of our bodies and inside of our cells just start to accumulate this damage as we get older. So DNA becomes damaged, the proteins or enzymes inside of our cells get damaged. Even the cellular membrane, the integrity of that membrane gets damaged, and it doesn't work as well to keep the outside world out and the inside world in.

Katie: Got it. So definitely, like, lots of different approaches, and you mentioned that there's probably something to be learned from all of them. What view do you take personally when it comes the aging, and which of these are the most important to understand then and start to mitigate?

Dr. Dixon: Yeah, it comes back to that research that I referenced by Professor Harman back in 1954. He postulated probably the most sound theory of aging, and that being the free radical or oxidative stress theory of aging. And in a lot of ways, many of these other theories of aging really kind of playoff of that oxidative stress theory of aging. So you can think about the damaged theories of aging, the loss of cellular communication and, especially those biochemical molecular and cellular theories of aging and really where that research is centered and what we can best do to protect ourselves and set ourselves up for optimal health in the long term is just really making sure that we're eating a healthy diet. And then luckily, there's been some great scientific advances in about the last 10 years that have shown us that there is even some pretty fun things that we can do around nutritional supplements to support, especially our body's own inherent anti-oxidant detoxification defenses.

Katie: Got you. Okay. So I think that's a perfect place to start diving in and going deeper, because there's … When you start reading the research and, especially just reading sources online, there's a lot of theories about different ways that we can do that. Of course, when you talk about free radicals, antioxidants come to mind. That's a big buzzword with oxidative damage and free radicals. But I also know that there's a lot of discrepancy in, like, the potential measurements and research related to antioxidants. And some people say, "Too much of a good thing can be a bad thing." So what's your take on ways that we can reduce that cellular damage, and are antioxidants the answer?

Dr. Dixon: It's a great question. And, you know, you're absolutely right. The scientific literature is very muddy when it comes to taking, especially high doses of antioxidants. And can we really extend healthspan and even, lifespan. If you go on and read some of the research on the National Institutes of Health, specifically from the centers for complementary and alternative medicine, they talk about … There's a line in one of their statements that just says, "In research studies that have been done in thousands and thousands of people, there is no scientific evidence that … especially high dose antioxidants supplementation is actually going to have a beneficial effect on human health and disease."

My view, as I read the scientific literature and things I've incorporated into my life is that, you know, we absolutely have to get the basics, whether it's from our diet or from our nutritional supplement, and that does include some antioxidants, and it's what we call the vitamin antioxidant. So these antioxidants that are absolutely essential for life, right? They're actually working as a vitamin. And then they have this sort of side effect, if you will, of actually being an antioxidant. So if we take vitamin C, for example, vitamin C is an essential nutrient because it's playing a role, a direct role as a cofactor which means it's absolutely required for the activity of an enzyme to work. And it's required in at least 15 different mammalian enzymes.

So if we stop taking vitamin C, those enzymes stop working and that ultimately compromises cellular function. But when we're thinking about antioxidant protection and really, what is the best strategy, you know, a strategy that I love to incorporate personally, things that I've researched in the laboratory for many, many years is really trying to unlock the power that our cells inherently have. So what do I mean by that? It turns out that in our DNA and, specifically in our genes, we have antioxidant enzymes, and we also have detoxification enzymes. If you set the clock back to about 2007, just kind of as the Human Genome Project was kind of wrapping up and people started to really dive into, "Okay. What are all of these genes now that we can map, what are they actually doing?"

Well, they came to discover about that same time, 2006, 2007, that actually there's this massive interaction between the nutrients that we eat and our genetics. So basically nutrients can turn on genes, and then those genes are also affecting how we were metabolizing nutrients. And when you actually put these things in test tubes, whether it's these enzymes that are encoded in our DNA or whether we just put these straight antioxidants into test tubes, it turns out that this enzymatic activity, these enzymes that are found in our DNA are significantly more effective at detoxifying antioxidants, free radicals, and those other toxins that may be entering our bodies.

Katie: That's fascinating. Okay. So you mentioned that basically what we eat has the ability to turn on genes. And I'd love for you to explain this a little bit deeper. Basically I'm assuming that you're talking about the idea of epigenetics essentially, but for anyone who's not familiar with that concept, can you explain how that process works?

Dr. Dixon: Yeah, maybe I'm hung up on my scientific circles. But yeah, epigenetics is definitely influenced by the diets that we eat. But another complicated science word that maybe better describes what we're talking about here is nutrigenomics. So if you break that big word down into its two parts, nutri and genomics, it's really how nutrition and your genes are interacting. Maybe I'll take a step back. I mean, maybe scientists and medical professions in their arrogance, they love to break things down into as simple of pieces or parts as possible. A lot of this research really came out of the research that showed that high levels of fruit and vegetable consumption are actually incredibly beneficial for our health.

So in that scientific arrogance, scientists went into fruit and vegetables, and they tried to tease out and find the compound or compounds that might be responsible for that increase in health that we're seeing in the highest fruits and vegetable consumers. So they pulled out things like vitamin C. They pulled out things like fiber. And definitely, you can supplement with vitamin C, and you see some health benefits. You can supplement with fiber, you see great health benefits. But when you look at the research, it never really equated to the full effect that we were seeing with this fruit and vegetable consumption. So scientists were scratching their heads, thinking to themselves, "Well, there must be something else in these fruits and vegetables that are also providing health benefits."

So then instead of looking at the things that were present in the largest quantities in fruits and vegetables, they started to focus on compounds that were really present in really very small concentrations. If you think about what gives fruits and vegetables their bright vibrant colors, it turns out it's a lot of those same compounds that we're providing these health benefits. So in some studies that were conducted, they teased out these compounds from fruits and vegetables that give them their color. They start to test them in the test tube and yeah, in a test tube, they're working as very potent antioxidants. But what happened when they gave these compounds to people is they found that they were incredibly poorly bioavailable.

That means they weren't absorbed by our bodies or if they were absorbed, they were absorbed at a very low rate. More than that, when these compounds were actually getting into our bodies, our bodies were metabolizing them incredibly quickly and then excreting them incredibly quickly as well. So then how could these compounds that are one, present in incredibly low concentrations that we don't absorb very well and then are metabolized and excreted very quickly, how could they possibly be having any sort of health benefit? Well, it turns out what researchers found is that a lot of these compounds are actually binding to what we call receptors that are either sitting on the outside of the cell membrane or are floating around inside of the cell.

An easy way to think about receptors is just being little sensor molecules. And so when you get the right compound that's gonna bind to the sensor molecule, what ends up happening is we start a chain of events. A lot like knocking over, let's say, like, a line of dominoes. So you push over the first domino, you get this chain of events that happens, and then at the end of that chain, something happens. So when we're talking about what's happening in our body, a lot of times, that's actually a protein, right, going into the nucleus and actually flipping these switches on these genes that have been shown to have great health benefits. In fact, they're known as either anti-stress genes or maybe even more aptly named survival genes.

Katie: Got it. Okay. That makes sense. And it seems like a lot of this also goes back to inflammation which is a big buzzword right now as well. Is that part of this equation and if so, like, what are some things on either side of that equation?

Dr. Dixon: Yep. That inflammatory axis absolutely can be influenced by the foods that we're eating. Absolutely. So we can target them nutrigenomically. So maybe a lot of your audience might have heard of a protein called NF-kappa B. NF-kappa B really is the master regulator of our immune response. And it's determining whether or not we have an up-regulated or even hyperinflammatory response, but then it's also responsible for shutting down that immune response as well. And so when we're talking about inflammation, what we're really talking about is a balance. You know, think of a teeter-totter just kind of balancing there. If your immune system is completely shut off, then, you know, that's gonna compromise us to this outside world that's constantly trying to get in and invade our cells.

But then again, on the flip side, if you have too much inflammation going on, the scientific literature is incredibly solid on what hyperinflammation can do in its roles as it directly relates to health and then, especially, disease. You know, a few years back, there was a cover of "Time" magazine that just simply said, "The Silent Killer." And it was really just this kind of furnace that is inflammation getting carried away in our bodies and so left unchecked, inflammation can go on and have just massive consequences to literally every system that's inside of our bodies. So again, reaching for these compounds that can help regulate that protein NF-kappa B. And then there are some other things that we can do. We wanna make sure that we're getting plenty of omega-3 fatty acids.

When you look at the biochemical pathway, the different fats that we consume in our diet are going down inside of the cell. They tend to either be pro-inflammatory or anti-inflammatory. And so with our modern diets and most of us tending to eat pretty unhealthy, we tend to reach for foods in a box. We've really skewed the balance of our fatty acids to saturated fats and then omega-6s and omega-9s. So when we look at, again, all that scientific literature about the health benefits of omega-3 fatty acids, what's most likely happening is that we're bringing the balance of those pro and anti-inflammatory fats back into the balance that our bodies prefer to keep them at.

Katie: That's a great point. What are your preferred sources of omega-3s? Because I know this is also a controversial topic in… People saying, "A lot of them can go rancid if they're not carefully controlled, and some are not as potent as they claim to be." Is this better to get from food, or what do you look at for omega-3?

Dr. Dixon: Well, the best and maybe most convenient source of omega-3s would be those traditional fish oil supplements, I think, that we've all heard so much about. But exactly, the points that you raised are very valid. And unfortunately, and the nutritional industry, I hate to say it, but it really is buyer beware. And you're absolutely right that omega-3s are particularly prone to oxidation. So if they're not handled correctly, you've basically changed the structure of those fatty acids, and you're no longer getting what you think you're getting. So, you know, I encourage people that you have to spend a little bit of money. Just buying the cheapest thing that might be on a supermarket shelf isn't the best option.

Spend a little bit of money, make sure you're buying your products from a reputable high-quality manufacturer to ensure that you're getting those fatty acids. That's the simplest way. And maybe a simple check if people want to, maybe go into their pantries and see if their fish oil might be appropriate or not. But simply break open the capsule and smell it because they go rancid so quickly. And I think we're probably all familiar with what rotten fish smells like. So if you break open your fish oil capsule and it smells like rotten fish, then you've got a bad product on your hands. You know, there's great sources of omega-3s. I know, you know, a lot of people are choosing to be plant-based these days. If not, straight vegetarian or even vegan.

And there are some great vegetarian and vegan sources of omega-3 fatty acids. Things like flaxseeds, walnuts, they're fantastic sources of omega-3s. So we can get these from our diets as well if we wanna eat a lot of fatty fish. So it's not just eating fish two to three times per week, but it specifically has to be fatty fish like salmon, tuna, mackerel, sardines are a couple of examples. And then just making sure you're getting as well a lot of … mostly, nuts tend to be very rich in, you know, omega-3 fatty acids.

Katie: I think those are all such great suggestions, and I love the fatty fish idea. That's something I've adopted that I think is really inexpensive, easy way to get omega-3s is a few times a week, I will eat sardines, and I'll just make lunch out of a bowl of sardines and veggies and nuts and hemp parts and all kinds of stuff and then just kind of put olive oil on it. And you mentioned fat sources and how the American diet definitely skews towards, not just saturated fats, but even just, like, really unhealthy forms of saturated fats and also, omega-6 oils. A lot of guests on this podcast and a lot of resources I'm seeing are recommending the monounsaturated fats in much higher amounts. Things like olive oil and avocado oil. Is that your take on it as well? Are those the kind of fats we should be prioritizing?

Dr. Dixon: Yeah, it comes back to really what we were talking about initially with antioxidants. I think everything has to be in balance. So what I'm not a fan of is going to an extreme one-way or another. I mean, you can even make the argument that we need saturated fat as well. I mean, most of the fat that makes up our cell membrane is actually saturated fatty acids. But it's very clear that we've just become over-consumers of, especially unhealthy saturated fatty acids. So my best recommendation is just to eat a variety of foods. You know, don't really be afraid of anything but just eat things in moderation.

And then whenever possible, whenever time and convenience allows, reach for whole foods, so the actual original sources. You know, with our busy lives, that's not always possible. And I think that's a good time to start to consider nutritional supplements as the word suggests, right? The word supplement is supposed to be supplementing our diets, and if our diets aren't healthy and well-balanced, then any nutritional supplement in the world is not going to fix those core problems.

Katie: I agree, and I wanna get to specifics on supplements in just a minute. But first, I wanna pick your brain on a couple of other things. So a few years ago, when I had nodules on my thyroid and had Hashimoto's before I was able to get it in remission, one of the things my doctor suggested was to consume broccoli sprouts regularly which are a source of sulforaphane which, from what I've researched, is known to activate something called Nrf2. And I know this comes into play with this inflammation equation. And I'd love to really explain this, because I've never kind of teased this out on the podcast before. And I know this is something that you've done research in. So can you explain to us … first of all, is my understanding of this correct? And explain to us what Nrf2 is, and why it's important?

Dr. Dixon: Absolutely. So Nrf2 is a protein. So it's a protein that lives in our cell, and it's an interesting protein, and how it behaves in that. It's both…One of those center molecules or receptors that we were talking about. It's also really the signaling molecule itself, and then it's also the protein that can go into the nucleus, and it actually flips the switches of somewhere between 200 to 300 different survival genes or anti-stress genes. A lot of these tend to be antioxidant enzymes or detoxification enzymes. I'm impressed with your knowledge of sulforaphane, and, especially impressed with the source that you're going to. So broccoli sprouts have been shown to be the highest sources of sulforaphane.

You know, my recommendation if that's what some of your listeners are doing, you know, make sure you're chewing them up. Sulforaphane itself actually comes with another little molecule stuck to it. So it turns out you actually have to really chew any source of cruciferous vegetable that you're eating to release an enzyme that will remove that other molecule that's stuck to it so that you can actually get the healthy compound. What's so interesting and how this protein Nrf2 is working is normally it's found anchored to the cell membrane. And it's anchored by a very interesting set of chemical bonds. And the way that sulforaphane is working is that it's actually interacting with that chemical bond, and it's releasing Nrf2 from the cell wall, and it floats through the cell, gets into the nucleus, and turns on a bunch of genes like we're talking about.

A compound that I'm even more familiar with dates back to, gosh, many years ago now. But back when I was doing my graduate work, I studied lipoic acid, if you're familiar with that compound. That's just an absolutely … another amazing inducer of Nrf2. We can look at things like Coricidin, green tea, ashwagandha, Bacopa. There are a whole host of compounds that actually are activating Nrf2. And so if activating Nrf2 and turning on these antioxidant and detoxification gene is the strategy you want to employ, then my recommendation would be to look for a mix of healthy compounds that are known to activate Nrf2.

Katie: Got it. Yeah. I love it that you brought that up about having to chew the broccoli sprouts to activate the sulforaphane correctly. You can verify this for me. But to my understanding, you've got glucoraphanin and myrosinase in that equation, and it does have to be broken up in certain … and temperature can come into play, and there are things that can help with that. So I don't recommend it based on taste, but what I do to get enough of this is I will blend up a bunch of broccoli sprouts with some mustard seed powder which has some of those things that you need, and that help break down. And then the blending, I let it sit for a minute, and then drink it. From what I've read, that's supposed to make the sulforaphane more readily available.

Dr. Dixon: Yeah, Katie, I'm incredibly impressed. You are exactly right on all that biochemistry.

Katie: Awesome. Well, I'll put links, I've got posts on how to grow broccoli sprouts. I think that's one of those easy things we can all do in our own kitchen, and it cost literally, like, 50 cents to grow if you do it yourself versus buying them in a store, so that's an easy step.

This podcast is brought to you by Four Sigmatic… a company I've loved for years for their superfood mushroom based products. They use mushrooms like lions mane, chaga, cordyceps and reishi in delicious products. Did you know that mushrooms are more genetically similar to humans than plants are? And that they breathe oxygen and exhale CO2 just like we do but mushrooms spores can survive the vacuum and radiation of space. These amazing fungi are always a part of my daily routine in some way, usually with Lion's Mane Coffee or Matcha in the morning, Plant protein and mushroom elixirs like chaga and cordyceps during the day and reishi at night to wind down. As a listener of this podcast, you can save on all Four Sigmatic products. Go to foursigmatic.com/wellnessmama and the code wellnessmama gives 15% off

This podcast is brought to you by Wellnesse, a new company I co-founded to bring the best personal care products from my family to yours. Our whitening toothpaste is based on my DIY formula that I have been making and perfecting for over a decade. Now, after almost 100 rounds of tweaking the formula and thousands of positive reviews, I could not be more proud to share this with your family. Have you ever read a tube of normal toothpaste? I did when my older kids were little, and I found a warning that said, "Warning, keep away from children. Do not swallow. If ingested contact Poison Control or seek medical attention immediately." That seemed a little extreme for something that I was putting in my mouth and my children's mouth multiple times a day. And I didn't want my kids using something that often that I would need to call a poison control center if they accidentally swallowed. I set out to create a truly safe and effective alternative. And the Wellnesse Whitening toothpaste is just that. It's designed to support the oral microbiome and the natural process of saliva and teeth so that teeth can stay white and strong. This dentist approved formula is safe for the whole family and will leave your teeth shiny and your breath fresh. You can check out our toothpaste and our completely natural hair food hair care products at wellnesse.com. An insider tip, if you grab an essentials bundle or try autoship, you will lock in a discount so that you can try everything at a great price.

I'd love to now go a little deeper on the science of actually, like, slowing aging and fixing these processes, both in two ways. So I want to start practical and then move onto optimal. But when it comes to the practical side, I'm a big fan of 80/20 and doing the most effective important things that provide the biggest payoff. And I know that there are definitely some of these when it comes to the aging equation, both in supplements and other factors that come into play. So based on your research, if we were going to look at aging in kind of an 80/20 equation, what are those 20% of variables that we should focus on that have kind of 80% of the effects that we're trying to achieve?

Dr. Dixon: Yeah, the three things that are really at top of mind for me right now are still that free radical theory of aging like we were talking about. For me, it's also the mitochondrial theory of aging. And if your listeners aren't familiar with what the mitochondria are, it's really where the vast majority of our energy production is happening inside of our cells. They're literally these little nuclear powerhouses that are generating about 95% of all the energy that our body needs every second of every day.

And just to put in the context how important that energy production is, we basically make our body weight every single day in the energy currency, ATP that we need every single day. So think about how much energy is flowing through the mitochondria and all the work they're doing. And then something else that's caught a lot of attention for me lately is the molecule, NAD. I'm not sure if you're familiar with that or if your listeners are familiar with that. But some very interesting research around the health benefits of NAD and then, especially what's happening to NAD as we get older.

Katie: Yeah, let's talk about that. So I have some experience with NAD, and I know that there's a lot of research and kind of some controversy about NAD versus NAD precursors. I have done NAD IVs, which for anyone who is not familiar with that, it's an IV that contains NAD. And it's somewhat uncomfortable going in, depending on how quickly you do it. I also, one time and will never again, did a push IV of NAD and wished I was dying for a short amount of time. But then I've also done research into NAD precursors, which from my understanding, are various forms of vitamin B3, if I'm remembering that correctly. But let's talk about that. Explain what NAD is and also, what those precursors are in the body.

Dr. Dixon: Yeah, NAD, it's an incredibly interesting molecule, and it's absolutely essential for life. So you're right. We do make NAD from various precursors and like you said, vitamin B3 or niacin is one of those precursors. NAD's normal role inside of the cell turns out to be inside of the mitochondria, and it is intimately involved in all of that energy production that we need every second of every day. So normally what's happening is as we're eating food, our digestive system chops it up into its small little bits. It gets into circulation. Our cells ultimately end up absorbing these compounds.

And then the food tends to make it into the mitochondrial where most of our energy production is happening. It goes through something that's called the Krebs cycle or the TCA cycle if maybe you're as old as I am. And then basically the role of this Krebs or TCA cycle is to break the bonds of that food, and as you're breaking those bonds, effectively you're releasing the electrons from that chemical bond. One place those electrons end up is attached to NAD, and NAD acts as the shuttle molecule to get the electron into something known as the electron transport chain which is really trying to harness the power or the energy that's in that electron so that we could ultimately make ATP, which is the energy currency for the cell.

So it's vitally important if we were to shut off NAD synthesis, I mean, we would be dead in a matter of seconds. But some interesting research that has centered around what's known as caloric restriction. So we're talking about a diet, but we're talking about maybe the most severe diet that anybody has ever been on. We're talking about a restriction of 40% to 60% of the calories that we would consume every single day. So for me, at about 160 pounds, that would equate to eating right around about 800 calories per day. So I mean, incredibly calorically restricted. The research that has led to this kind of notion of caloric restriction initially started in yeast. Yeast is a fantastic experimental model, especially for geneticists.

So some geneticists embarked on these studies where they were calorically restricting yeast, and then they moved the studies into looking at worms or fruit flies, right, to more experimental models, mice, rats, even some primates. And then some people have even played with caloric restriction themselves. What's so interesting is when they found that we restricted calories by this huge amount, you got about the same lengthening of lifespan, so around the same 40% to 60% actual increase in lifespan. And it's really the only known non-pharmacological or nongenetic way that's been shown to increase lifespan. So, of course, scientists in their inquisitive nature wanted to know, "Well, how is caloric restriction actually eliciting these effects?"

These geneticists went in, and they did a bunch of studies. And then a long scientific story short, they found that there was this family of proteins known as the sirtuins. And when they genetically manipulated or even pharmacologically inhibited this family of proteins or enzymes and then they still calorically restricted these experimental models, they completely lost that extension in lifespan. So scientists then went on to study what's going on with these sirtuins and exactly how are they working. Well, it turns out the way that these sirtuin molecules are activated is by this molecule called NAD, so NAD is absolutely required for their function to occur. So if we kind of lumped together everything that's been shown as we're calorically restricting and you don't have a lot of those electrons around, your relative levels of NAD actually increase.

And NAD is no longer working to generate energy but actually becomes a signaling molecule to activate this family of proteins called the sirtuins. And then downstream, right, or a better way to say it is that these sirtuin proteins are actually controlling a number of different pathways and factors and enzymes that have been shown to have all sorts of different health benefits, and that's really why NAD has caught a lot of people's minds. You throw on top of that that NAD levels declined significantly as we age, probably starting sometime in our late 20s or early 30s and then by the time we're 60 or 70 years old, our levels can decline by as much as 60%.

Katie: Wow, yeah, that's really drastic. So there are things … I'm so glad you brought up sirtuin as well. That was one of my questions that I was gonna ask, because I knew that was a factor in this. But so basically there are things that we can do, supplements that help increase the body's NAD capacity essentially.

Dr. Dixon: Yeah, and you kind of alluded to one, and that's the precursor approach. And there's not just vitamin B3, but there are other related molecules that are out there that people are using as substrates. There are also intermediates. So when your cells are building NAD from scratch, it kind of has to go through this process. So people are also trying to incorporate, trying to kind of cheat the biochemical regulation that's going on by feeding the so-called kind of intermediates which can still be considered precursors. And then some things that's really caught our attention lately is leveraging also, a Nutrigenomix approach to look at the enzymes that are actually making NAD in our body. And are there ways that we can use nutrients to actually turn on those enzymes to ultimately increase the biosynthetic capacity of our NAD generating pathways.

Katie: That's fascinating. And I know one concern I've heard with certain NAD precursors and taking them in too large of a dose is that some people speculate that it can use methyl groups for, like, that conversion to happen. So that if we take them in too large of amounts, we can deplete methylation factors which can, especially be an issue if people who have MTHFR. Are you seeing that, are you concerned about that, or do you think that's only an issue with really big doses?

Dr. Dixon: Yeah. Again, it kind of comes back to the gist of most of the conversation we had. And that's just that everything needs to be in balance, right? Too little of something is bad, right? Let's use a simple analogy with water, right? Dehydration is terrible, but you can actually drink too much water and kill yourself. So we need to be within this sweet spot of the bell curve, and the bell curve lives everywhere in biology. When it comes to the precursor notion specifically, right, I'm just trying to make sure that I'm getting somewhere slightly elevated over kind of either the RDA or the recommended daily allowance or daily recommended intakes, however, you wanna say it. I'm not a fan or supporter of mega-dosing in any way.

But if we come back and look at the biochemistry with how a lot of these pathways are working, a pathway can only work as fast as its slowest enzyme. I hope that makes sense. So any biochemical pathway in our bodies can only work as fast as the slowest enzyme. So you can kind of think almost like you create a traffic jam in this biochemical pathway or maybe another way if you can think about it in your mind's eye is think about a funnel. And if I were to pour water into the top of a funnel, water can only move to that funnel as quickly as its narrowest point.

So at some point, we're gonna overload the system and those compounds that we're thinking or we're taking that we think is gonna have an effect on one end isn't gonna make it into that biochemical pathway, and it's gonna float around on our bodies, and who knows have what type of effect. So, you know, our approach is to look at it both ways, so providing precursors to some extent, not in massive megadoses. But then what are nutrients that we can utilize to leverage that genetic machinery, turn on that genetic machinery to increase really the biosynthetic capacity of the NAD so that the precursor that's around will ultimately get consumed in the way that we want it to be consumed.

Katie: Got it. Okay. That makes sense. So then from there, we talked about the practical. What if you could create an optimal scenario for someone to slow aging and to improve all of the things that we've talked about, both with supplements, with diet, and with lifestyle, what would that look like?

Dr. Dixon: I think if we want to really increase, not just longevity, but the thing that I'm most focused on right now is healthspan. I think if we can keep ourselves healthier for longer, I think, the side effect is gonna be added years to the end of our lives. You know, the scientific literature is just incredibly discouraging. Every American especially, if not every individual living in a modern society tends to lead their last 10 years of life suffering from some sort of disease or disability. And I just think my best advice is not to accept that as our norm. So the things that we can do in our lives to shorten that length of morbidity or disease or disability, just think of the quality of life.

I mean, if we can take that 10 years and shorten it to 5 years or 5 years down to 1 year and not to get too morbid, but I love to take just a big nose dive into my grave, right? I don't wanna scratch and claw my way there. But when we wanna look at what are the things that we know in humans that are having the best effects for our healthspan and our lifespan, there's a lot of different names floating around for the concept. I've heard it referred to as Blue Zones. But really, what these Blue Zones are longevity hotspots. And it turns out that there is just a very small handful of them around the world. There's one in Japan. There's one in Greece. There's one in Italy. I throw one in there in France as well. There's one in Costa Rica, and there's one in Southern California.

So researchers have gone in and they've looked at all of these different populations and ironically, they tend to be very isolated populations. So they don't seem to be as affected by a lot of our kind of new-age cultural norms. But when they kind of look at the aspects of each of these populations, there's definitely unique aspects to each and every one of them. In fact, a lot of the diet fads that we've seen in probably the last 10 or 20 years are because of these longevity hotspots. So if you take the one in Japan, for example, that's where really, sushi got really popular and eating the fatty fish. If you look at the populations around Italy and Greece, that's really where the Mediterranean diet came into play. We can talk about the French paradox also, coming out of France as well.

But some of those newer longevity hotspots that have been found in Costa Rica and California, what they've really focused on is really movement and also, decreasing stress. So when we lump all of this research together from these longevity hotspots, the things that they all do share is that they obviously don't smoke. They tend to eat a very plant-heavy diet, if not, exclusively plant-based. They have constant moderate physical activity. So what does that mean? It means, they're just constantly moving. They're not doing extreme workouts but just moving their bodies, and it could be nothing more than just walking around town or walking to their friend's house. This is a little bit different, but they also tend to eat a lot of beans or legumes.

So they're, you know, great sources of protein but also, great sources of fiber. Coming back to one of those psychosocial theories of aging, they also make family and friends a huge priority. I don't know if you or any of your listeners maybe have been to France or Italy. But goodness, it's tough to get out of a restaurant in two hours for lunch, and you're probably sitting down for dinner for three or four hours, right? They make a big ceremony around food, getting everyone around the table, and just having fun, laughing, joking.

Something else these populations have in common is they slow down, and they try to minimize the stress that they have in their lives. So when we really look at those basically, all six, seven, eight things, right, so family, no smoking, plant-heavy diet. They eat a lot of beans. They're socially engaged in their environment. They're constantly moving, and they just try to decrease the amount of stress and slow their lives down. So that's my advice for your listeners.

Katie: I love that. And I love that it always comes back to community in some form. That's something that I've talked about so much in the last couple of years, especially that when we look at the data, it really is astounding. How important having those really solid relationships and spending time with people. That really is a dramatic indicator of health like you mentioned, and so I think you're right. I think it's important to have all those dietary strategies in place. And in today's world where our food system is so depleted, it's also important to take supplements in certain cases. But also, we can't minimize those lifestyle factors like just being outside and moving like we're supposed to move and spending time with people and having great relationships. So I love that you tie those in as well. Where can people keep learning more about these topics and keep learning more about you?

Dr. Dixon: We have a wonderful blog on our website where we're talking about all aspects of health. We talk a bunch about theories of aging and the different things that people can do to help set themselves up. You know, all those lifestyle, things that we're talking about. When supplementation makes sense. What supplements you should be reaching for. So you can find that blog on our main website at LifeVantage, so L-I-F-E and then Vantage, V-A-N-T-A-G-E.com. Look for the blog link there and, you know, we encourage everyone to also, subscribe to really all of our social media channels where we're literally everywhere, so Facebook, Instagram. You can just search LifeVantage, and you'll be able to find us there. We're constantly trickling out all sorts of content around healthy lifestyles and nutritional supplementation.

Katie: I will make sure that is linked in the show notes at wellnessmama.fm for any of you if you're listening while you are driving or running or doing any other activities, you can find those there and also, link to my post on a lot of these topics that we have talked about. Another question I'd love to ask at the end, somewhat unrelated or it might be related is if there's a book or a number of books that have had a really dramatic impact on your life. And if so, what they are and why?

Dr. Dixon: Gosh, mine tends to go back and forth to what I'm currently reading. But if I had to choose one book to recommend, I would have to go with "Influencer." I'm not sure if you're familiar with that book. But it's actually "Influencer: The Power to Change Anything." It's such a fascinating book, and it really kind of breaks down really kind of the psychology of where people are at. If people aren't familiar with that book, it really looks at a couple of just seemingly impossible life circumstances that humans have found themselves in and then really just trying to break down the human behavior that's responsible for those behaviors, and then ultimately how people could intervene to completely reverse those behaviors.

And I think the lessons in that book are just so incredibly powerful for literally every aspect of our lives, so whether it's eating healthy, exercising, if we want to maybe lose a couple of pounds, just thinking about those key decisions that we're making, and how we can really set ourselves up to overcome really our own human psychology, I found that book to be incredibly powerful.

Katie: I love it. And that's a new recommendation. I will make sure that that is linked in the show notes as well. But Brian, this has been a fascinating episode. I loved getting to deep dive with you into some of these topics, especially ones like Nrf2 and sirtuins that I haven't talked about here before. And I'm really grateful for all the work you're doing on spreading the word about how we can stay healthy as we age gracefully.

Dr. Dixon: Well, Katie, I appreciate that very much, and I'd like to applaud you as well for all that you're doing to help get, you know, useful and practical information out to your listeners and really on the simple things that people can do to improve their lives in every sense of the word. So thanks for all you're doing.

Katie: Thank you. And thanks as always to all of you for listening, for sharing one of your most valuable assets, your time, with both of us today. We're so grateful that you did and that you were here, and I hope that you will join me again on the next episode of "The Wellness Mama Podcast."

If you're enjoying these interviews, would you please take two minutes to leave a rating or review on iTunes for me? Doing this helps more people to find the podcast, which means even more moms and families could benefit from the information. I really appreciate your time, and thanks as always for listening.

329: How to Slow Aging, Fight Inflammation, & Improve Cellular Signaling With Brian Dixon, Source:https://wellnessmama.com/podcast/brian-dixon/