Episode 196: Fasting, Cellular Health, and Aging Well w/ Dr. Christopher Rhodes

In this episode of the Aging Well Podcast, Dr. Jeff Armstrong explores the science of fasting, cellular health, and longevity with Dr. Christopher Rhodes, co-founder and CEO of Mimeo Health. Dr. Rhodes discusses how fasting and fasting mimicking diets can enhance metabolic health, influence cellular processes, and potentially extend lifespan. Learn about the various types of fasting, their benefits, and the innovative approaches Mimeo Health is taking to support healthy aging. Dr. Rhodes also shares his journey into the field and discusses the promising future of fasting as a tool for disease prevention and longevity.

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Transcript

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This episode of the AGMR podcast we delve into the science of fasting, cellular health, and longevity with Dr. Christopher Rhodes, co founder and CEO of Mammalian Health. Dr. Rhodes shares insights into how fasting and fasting mimicking diets can improve health. Transcripts can profoundly influence cellular processes, boost metabolic health, and potentially extend lifespan. We explore the unique approaches Mimeo Health is taking to support healthy aging, discuss the differences between intermittent and prolonged fasting, and consider the future of fasting as a tool for disease prevention and longevity. Whether you're curious about optimizing your health or looking for innovative ways to age well, this episode offers valuable perspectives from a leader in the field.

jeff_1_09-18-2024_110403: 0:44

Dr. Rhodes, welcome to the Aging Well podcast. Let's begin by having you tell us a little bit about yourself and how you came to be interested in the cellular health benefits of fasting.

dr--chris-rhodes_1_09-18-2024_110403: 0:55

Thanks you so much for having me. I'm happy to be here. So a little bit about me, I got my B. S. in biochemistry from Loyola Marymount University down in L. A. then when I got out, like a lot of college kids didn't really know what I wanted to do, knew that it wanted to be something in research, but, Wasn't entirely sure what my passion was. So I took a immunology fellowship at Stanford where I just kind of started pouring through all the papers. I could get my hands on going to all the seminars. I could try and figure out, you know, what would light me up from a research perspective and eventually came across the healthy aging and longevity space, which I thought was really fascinating because it used to be a myth and legend and Ponce de Leon and the fountain of youth and all that, but is now this very. active, very rigorous area of scientific research that, you know, even since then has become bigger and bigger and bigger. Um, and when you're in that space, eventually you come across caloric restriction because they're the only ways that we know of to really reliably extend lifespan in animal models. And when you look even beyond the lifespan extension data, you also see that. Fasting can help to treat prevent or delay most major diseases as well. And that extends to the clinical human side of things. what I found most fascinating about that was that it does. all of that stuff, all of the lifespan extension, all the health span extension, all the disease, you know, prevention actually adding anything into the system, right? So it's not this wonder drug or this superfood that we're taking and then it's doing all the work, but somehow fasting is activating this. dormant longevity bio program that we already have inside of us, but just isn't ordinarily turned on. And when that clicked for me, it made me mad because I was like, all right, great. So my body knows how to be 120 years old, in perfect health, but it's just not doing it. that was the catalyst for me to, direct my research focus towards fasting and figuring out, what is happening in the human body during a fast that's activating these great regenerative and pro longevity pathways. is there a way we can, turn those on, on demand so that we can get those same benefits of fasting, those same cellular health, longevity effects, but without actually having to fast.

jeff_1_09-18-2024_110403: 3:23

Okay. before we start our conversation about fasting How do you define aging?

dr--chris-rhodes_1_09-18-2024_110403: 3:28

Yeah, I define aging well as probably how a lot of other folks would define it, you know, a health span, right? So, my mom used to say this thing that I always love, she was getting up into her later 60s and she told me, one day, when we were talking about it, you know, I don't really feel any different than when I was 25, mentally, I feel the same. I don't really have any cognitive slowdown. I don't really have any health problems. All my joints still function. I'm still moving around just like I was. So that 40 year gap between then and now, I just haven't really noticed a difference in my functionality or my health. And that, to me, is, aging. Well, Where you can just, have a 40 year blip where it's like, what happened? I don't feel any different. Right? So that's really what I would say keeping that functionality, keeping the speed of cognition and extending it out as long as we possibly can. the best analogy that I have for it is that, the way I think everybody really wants to go out. Is kind of like, you know, we want to be 98 years old, a hundred years old, whatever it is. And, you know, still running a marathon. And then, at the peak of our functionality, just immediately fall off and drop dead. And we have no conception that it even happened. So that would be aging well for me.

jeff_1_09-18-2024_110403: 4:37

that's kind of what I want to do I want to do something like run a marathon or whatever and come home sit in a recliner Go to sleep and not get up but be like 120 when I do it

dr--chris-rhodes_1_09-18-2024_110403: 4:47

yeah, exactly. And I think that's a much more approachable goal than it has been in the past because not only, are we finally getting on the train of healthy aging and longevity being a legitimate scientific field, but the level of advancements that are going to be made in the next 10 20 and 30 years are going to be Exponentially, accelerated because of the advent of A. And all the other technologies that are now getting stacked on top of all of this research. So I think that we now actually have the robust capabilities to track this multitude of data that goes into how we age and the entire complex bio systems of the human body that we can make better interventions than we've ever been able to do before.

jeff_1_09-18-2024_110403: 5:33

And I think the term longevity is just starting to really catch on. But in reality, the research and the activities that we're doing to live longer are actually getting ahead of that. And we're really talking much more about health span now than simply just longevity, because we've been able to keep people alive with medications for decades, but now we want to get them living well into those eighties, nineties and hundreds.

dr--chris-rhodes_1_09-18-2024_110403: 5:58

Exactly. Quality of life is very important. And that's usually something I hear a lot of pushback for in the longevity field, right? Is that misalignment between lifespan and healthspan, that lifespan, healthspan gap. And that's a very scary prospect, right? Ideally, like we were talking about before you want it to be healthspan and lifespan are exactly aligned, right? So you go out at the peak of your functionality, you never really experienced disease. It's just kind of like. you drift off and you never wake up. the concept of, your lifespan being, one year, two years, three years longer than your health span, that's the thing that really scares people, is that they will be unwell and that they'll be infirm and just kind of hate life until they die.

jeff_1_09-18-2024_110403: 6:37

We talk a lot about, you know, the four ages, First age is kind of that age of dependency is your kind of child, you know, birth through about high school, college, where you're dependent on your parents and somebody else to kind of provide for you. And then you have your second age when you're kind of out in independence, you've graduated from school, you got a job, you're starting a family, you're starting to do the things that are going to begin to build the finances and the wealth and the future for yourself. And then you get into third age, which is that age, of retirement and where you're able to enjoy your life because you've built up the finances And then fourth age is that age of decline and decrepitude. And that's where we really want to eliminate the fourth age altogether if we could.

dr--chris-rhodes_1_09-18-2024_110403: 7:21

Yeah, exactly. it's the age that nobody wants, so let's, just minimize it as much as we can.

jeff_1_09-18-2024_110403: 7:26

how does fasting or fasting mimicking diets affect cellular processes like autophagy? And how does this contribute to overall health and aging?

dr--chris-rhodes_1_09-18-2024_110403: 7:37

Yeah, great question. So it basically comes back down to these conserved evolutionary survival mechanisms that, you know, we've had coded within ourselves, probably, you know, since we were bacteria evolving out of the, out of the celestial mercury. So, fasting is interesting because it turns on that survival network. it's a signal, to your cells that the environment is not great for Bringing in the next generation, There's no nutrients around. So a kid in this environment, it would probably die because there's not enough resources to be able to sustain it. focusing on the next wave of progeny, right? running dirty, running lazy, as we often do in a fed state, because there's plentiful nutrients around, and we don't have to turn on things like metabolic efficiency or, care that much about if we're making too much protein or if we have dysfunctional organelles, if something goes wrong with these cells, we have plenty of resources to make a new and more functional one. So, in that fed state, we're usually running more dirty in a fasted state. It's really the opposite. not focusing on the next generation. We want to focus on keeping this generation alive as long as possible. So that we can go and find a new area where there are abundant resources and it would be beneficial to actually, you know, get the next generation out there. from a cellular perspective, what that's going to do is turn on a lot of metabolic efficiency programs. We're going to use less energy, and we're going to be more efficient in the energy that we do use. We're going to turn on those cellular processes like autophagy, right? That's our cellular recycling process. So we can break down, over abundant proteins, dysfunctional proteins, dysfunctional organelles into their constitutive parts, and then use those resources to create new functional ones. we're also going to decrease the amount of protein that we're making. decrease the amount of DNA that we're weaving and unweaving which helps to prevent damage over time, right? Because every time we replicate DNA, there's always some damage that happens in repair that we have to do. We're also going to turn on cellular stress resistance genes help keep the cell protected and more resilient than it would be otherwise. Because again, if it dies, we can't Make a new one because we don't have the energy available Then we're also going to be activating more pathways that help to promote that cellular stress response. We're going to be producing less metabolic waste over time. So we're not damaging ourselves. and that's kind of really how fasting and nutrient deficiency. Well, let's say not say nutrient deficient. Let's say energy restriction. Energy restriction is how all of this comes together and turns on that, survival and longevity mode. Because instead of focusing on, oh, we'll just, you know, create new cells or something goes wrong. We focus on maintaining the cells that we currently have, and that's ultimately what longevity is. It's not constant turnover of cells because that wears them out more quickly. Instead, it's let's take the cells that we currently have and make them survive as long as possible.

jeff_1_09-18-2024_110403: 10:52

how critical is metabolic flexibility on the aging process?

dr--chris-rhodes_1_09-18-2024_110403: 10:57

Oh, it's definitely critical, right? especially in the context of fasting, because you need to switch between glucose metabolism and, fat metabolism, ketone metabolism, protein metabolism, you can see this. on a cellular level too. a lot of our cells some are not super metabolically flexible. the best example of that is the brain. The brain always has to run on some level of glucose. it can, adapt to around 50 percent of its energy from glucose and 50 percent from, ketone bodies, it still has to rely on glucose, whereas other cells in our body, like immune cells, can survive on anything. They can do glucose metabolism. fat metabolism, ketone metabolism, protein metabolism. And so that's that's something where. need that kind of flexibility because the immune system is so important, right? It needs to be able to do its job in any environment and the micro environments that it's going to go into within your body are going to change around and, you know, the, The metabolites available to them are going to shift, whereas the brain, it's also very important, right, but its environment is more or less always going to be the same. So it can have that glucose dependency without it going too far in a singular direction.

jeff_1_09-18-2024_110403: 12:07

Okay, our listeners and viewers might be wondering, what is the difference between caloric restriction, fasting, and fasting mimicking?

dr--chris-rhodes_1_09-18-2024_110403: 12:15

caloric restriction is, just what it sounds like, restricting the amount of calories that an organism or that a person is actually taking in, and that's typically done on a chronic level. in the literature is that when you do something like, you know, lifelong caloric restriction. you can usually get, a pretty one to one ratio of lifespan extension. So what that means is if you reduce an organism's typical calories by 10%, you can usually see a 10 percent increase in lifespan, 20%, 20%, 30%, 30%. And that holds true, usually up until the point of malnutrition, right? Where you just really are not getting enough calories to sustain the organism where you're not getting enough. micronutrients in order to keep proper cell function alive. Fasting is different than that because fasting is just all about controlling meal timing, right? So fasting doesn't necessitate caloric restriction. and there have actually been multiple studies have shown that Fasting can have lifespan and healthspan extension effects, even in the absence of any kind of energy restriction. So while caloric restriction and fasting are, you know, similar in a certain sense in that they're controlling your food intake, they're also independent of each other and have distinct effects. fasting, you know, even in the absence of caloric restriction can still extend lifespan by, you know, 20 or 30 percent and at the extremes when you're combining both fasting and caloric restriction together, then you can get things like, you know, 50 to 80 percent lifespan extension. For fasting mimicking, that's a definitely like more emerging field, right? There are basically two companies out there that are doing fasting mimetic stuff right now. one of them is us, Mimeo, and then the other one is El Nutra and Prolon that makes the fasting mimicking diet. And the purpose of Both of ours in, although we're doing it in different ways is to recreate these beneficial effects of fasting, but without actually having to do true 0 calorie water only fasting in prolon's case, they're doing it through a diet. So, it's a 5 day program where. You're still eating food, but it's very restricted. You're typically not eating more than, 700 calories a day throughout this five day period. it works really well. They've got a lot of clinical studies on there, and it works really well because, you know, at the end of the day, you are fasting to a certain degree, right? You know, those 700 calories that would be like around 1 meal a day. if we're doing it on a, you know, on a fasting basis, right? there's definitely positive effects that you can see they're also using a specialized diet to make sure that we're not going through the typical, fed pathways. So we're restricting glucose, macronutrients and micronutrients in this specific way to kind of recreate fasting without actually needing to fully fast. With Mimeo, what we're doing is taking a little bit of a different approach. So our approach is what's called a biomimetic approach. we're really trying to look at what happens in the body during a fast, and find out how we can recreate that at a molecular cellular level, while still being able to eat. we're taking molecules that the body naturally produces during a 36 hour fast and giving them back to people as a supplement, which then raises their concentration in their body, even when they're eating a meal, but activates those similar fasting pathways and gives you the benefits of fasting, even when you're eating.

jeff_1_09-18-2024_110403: 15:58

what specific cellular mechanisms does MIMEO Health target in order to enhance longevity and support healthy aging?

dr--chris-rhodes_1_09-18-2024_110403: 16:06

there's definitely quite a few. we're targeting increasing autophagy via the spermidine that's in our formulation. We're also targeting the N. A. D. Sirtuin pathways through the nicotinamide that's in the formulation. the O. E. A. And the P. E. A. in there have a very robust, kind of molecular pathways behind them, but they're really good at controlling chronic inflammation, as well as is helping to relieve neuro inflammation at the same time. So they're cox one and two inhibitors. So kind of like your body's natural, your natural ibuprofen or aspirin, right? And then PEA itself is a CB1 CB2 inhibitor. It's involved in the endocannabinoid system. kind of like your body's natural CBD to a certain extent. So it's really helping to, relieve pain, increase joint health, enhance mood and cognition. A lot of interesting studies are coming out with PEA. showing it has broad spectrum effects across multiple indications. we're also targeting, PPAR alpha, which is another one of those broad spectrum molecular signalers, but basically helps to promote fat specific metabolism and lipid peroxidation while also helping to maintain, cell integrity. Helping to activate some of these stress resistance genes. and then we're also a specific molecular pathways that are related to, Oh, sorry. Totally. It's actually totally flew out of my head. but we're, the, like the main, the main point of all of this is that we're really targeting things that are activated by, by fasting, right? Oh, AMPK, this is what I'm thinking of. So like AMPK, ERK these, antioxidant pathways that are really important for stress resistance as well. And then AMP kinases, of course. one of the ways that fasting helps to promote longevity because amp kinase helps to inhibit mTOR and kind of activate more of these beneficial energy conserving, pathways.

jeff_1_09-18-2024_110403: 18:32

So from a scientific standpoint, what studies have been done to provide evidence as to how that specific memetic combination actually enhances longevity and healthy aging in humans.

dr--chris-rhodes_1_09-18-2024_110403: 18:46

Yeah, for sure. So we've done a couple, there was the original, discovery study that we did where we looked at, people in a baseline state, overnight fasted state versus a 36 hour fasted state. That's where we identified that the human body produces a lot of these unique metabolites that are only upregulated during fasting. And those were the ones responsible for activating all of these beneficial cellular effects, right? When we screened through those molecules, we were able to find this synergistic combination of four of them that ultimately went into the mimeo formulation that could recreate those beneficial cellular health effects. So the same anti inflammatory, antioxidant, cellular protective, benefits the same cardio protective benefits. we were also able to show that combination of molecules could increase lifespan in model organisms by 96 percent just through supplementation. No fasting, no caloric restriction of any kind, just they were living their normal lives, but with supplementation with the MIMEO formulation and lived almost twice as long. after that did a pilot clinical study, basically looking at the MIMEO formulation alongside food intake and essentially showed that. When people eat food alongside a placebo control, there's a big loss in plasma functionality, where their plasma becomes pro inflammatory less antioxidant, less cardioprotective, and their metabolic markers are all over the place, You're getting thrown out of homeostasis because that's. what happens during the postprandial response, right? You have nutrients and foreign molecules coming into the body, kicking off immune reactions, and your body has to deal with all those, that flood of glucose and protein and macronutrients and kind of put it where it needs to go. it needs to focus on that. So the rest of the functionalities of, you know, maintenance, rest and repair get shunted off to the side. What we saw with the mimeo formulation when they ate that same meal was that we could prevent all of that loss of function and add gains of function on top of that, that mimics what we saw during an actual fast. So, instead of being pro inflammatory, their plasma became anti inflammatory antioxidant and cardio protective. in the acute sense, we could. use mimeo to help prevent a lot of these negative impacts of eating while mimicking the beneficial effects of fasting. We've also done a, a case study with, Dave Petrino lab out of Mount Sinai, where we had, folks come in and do an eight week supplementation study with Mimeo and tracked cardiovascular markers, metabolic health markers, hormonal markers, as well as looking at before and after on biological age. And what we saw there was that, eight weeks of Mimeo with nothing else going on, no changes to diet or exercise or anything like that, was able to dramatically improve, Cholesterol levels, HDL levels, LDL levels, triglyceride levels. We were able to, reduce glucose levels. We were able to reduce HbA1c levels. We were able to increase, testosterone levels by 50%, but then really interestingly, we were also able to reduce biological age in humans by two and a half years in just that eight week timeframe.

jeff_1_09-18-2024_110403: 21:56

one concern I have with any oral supplement is, whether they survive the gut.

dr--chris-rhodes_1_09-18-2024_110403: 22:00

Oh yeah.

jeff_1_09-18-2024_110403: 22:01

So can you, be certain that the bioactives that you have identified, you know, was it spermidine, nicotinamide, and then I'm just going to say PEA and OEA because those are a mouthful to say, but, do you have evidence that they're actually being absorbed into the gut?

dr--chris-rhodes_1_09-18-2024_110403: 22:15

in that pilot clinical study that we ran, we looked at, both the functionality of the actual plasma, Which we saw a change in response to supplementation, but then we also did what's called pharmacokinetics that's essentially just looking at. if we take these things, can we see them appear in circulation? And how long do they stay in circulation before disappearing? we saw that, the molecules themselves come into the body. appear in circulation after around 40 minutes to one hour, and then stay elevated in circulation for around four to six hours we were able to see that, yes, in the form that we are giving it to people, we can see these metabolites actually show up in circulation. And then, beyond that, they are having this effect on. functionality, right? That anti inflammatory capacity, antioxidant capacity and cholesterol efflux capacity.

jeff_1_09-18-2024_110403: 23:05

And so with four to six hours in the bloodstream, that means probably a couple of times a day is. the dosage rather than just once a day.

dr--chris-rhodes_1_09-18-2024_110403: 23:12

all depends, right? there's a little bit of a nuance to that as well, Yes, you have things that are elevated in circulation that then disappear from circulation, but that doesn't necessarily mean that they're depleted from the body. It just means that, you know, they've been taken up by yourselves and are being processed and doing the work. Right. So, while the, yeah, while the circulating half life is four to six hours, I think they have a bigger impact, on cellular functionality throughout the day as the cells take them up and utilize them.

jeff_1_09-18-2024_110403: 23:41

And so that takes me to the next question, from a cellular health perspective, what are the differences between intermittent fasting and prolonged fasting? Because I know you talk about it like a 36 hour fast. We talk about intermittent fasting is like the, you the catch all now. It's like what paleo was a few years ago and I don't think a lot of people fully understand what it really means to intermittent fast.

dr--chris-rhodes_1_09-18-2024_110403: 24:05

Yeah, I would definitely agree with that. There's a lot of contention within the fasting scientific community about what are we actually studying here? And that's one of the reasons why typically when you see studies that come out of, intermittent fasting, they can be very variable The results that they're getting So we see these kinds of things all the time where it's like, oh, intermittent fasting has no benefit, or it doesn't have any more benefit than just normal caloric restriction But usually those studies are done on the shorter stages of fasting where it's more of a 16, eight style. So you have that 16 hour fasting window and that eight hour eating window. And that's usually, glorified skipping breakfast to a certain degree. Normally what we're all going to experience in our daily lives is somewhere between a, 10 to 12 hour fast on a daily basis from whenever our last meal was, and then we went to sleep and we didn't eat again until our first meal the next day, which is breakfast. Right. usually that's going to be 12 hours anyway, so adding an additional four on top of that isn't really going to do much from a biological perspective. in order to really enter into fasting metabolism, you have to go for at least 24 hours of fasting to deplete your body's stored carbohydrates, its glycogen stores. and before that time, your body's basically just going to be running as normal, right? It's going to be reliant on glucose metabolism. your brain's not going to go through any kind of metabolic flexibility or adaptations Your body's not going to go through any kind of metabolic changes or adaptations. It's just going to keep relying on the glucose that it already has in there. As a simple and easy fuel source that is depleted, though, then your body has to actually switch over to more of the ketone metabolism relying on endogenous energy stores like our fats and our proteins to really run the system now that we're depleted of glucose. And that's really where you start to see the true blue fasting metabolism. typically when people say intermittent fasting, we are talking about, 16 8, or even, one meal a day, those are going to be the shorter ends of the stick that's going to be much more similar to normal fed metabolism, especially that 16 8 style. Prolonged fasting is where, We're going to see anything kind of beyond 24 hours of fasting. So a 36 hour fast, a 48 hour fast, a 72 hour fast. And this is where you see the most robust benefits to, um, everything that we're really looking at, especially in terms of health and longevity in the literature, alternate day fasting, which is essentially. A 36 hour fast followed by a single day of eating, then a 36 hour fast over and over again for the rest of the organism's life is where we have seen the best lifespan extension in animal models. And that's because you do get the activation of autophagy. You do get that full molecular and metabolic switch over to fasting metabolism. You do activate all of those metabolic efficiency and cellular stress resistance and anti inflammatory pathways that we've been talking about. there's a lot of benefits to be had from a 36 hour fast. Then, as you get into the deeper stages of fasting, the 48 hours and the 72 hours, that's where you're really going to enhance autophagy. Autophagy will be, starting out in a 36 hour fast, but it'll really get ramped up around that 48 hour mark is where we've seen autophagy peak. and then a 72 hour fast is where we've seen really good data in terms of, creating benefits like, helping people sorry, We're going to be a 72 hour fast have been really helpful for cancer chemotherapy, so it helps to sensitize cancer cells as well as make the host cells more resilient to the chemotherapy. So you can get better results off the chemotherapy while also helping to decrease the actual side effects. And then this is also where we've seen the immune cell regeneration that can be really helpful for auto immune diseases happen. because you go from, these auto reactive T and B cells that are, attacking your own systems, those kind of get knocked down and we go back to the original stem cells and regrow our immune system a little bit. So it's less auto reactive.

jeff_1_09-18-2024_110403: 28:25

it would seem from a standpoint with the more frequent shorter fast, even though it works very well in the animal models, it's not so much suitable for the human model because of the complexity of our lives. you have athletes, you have individuals working and doing so many different things where our energy demands are different than those animal models. it seems like the more prolonged fast on a more periodic basis is going to have better overall health benefits, more comparable to what we see in terms of longevity in animals. Would you agree with that?

dr--chris-rhodes_1_09-18-2024_110403: 28:58

The longer fast you can do in a more condensed period, You're going to be more chronically activating that cellular longevity and survival program, with the shorter term fast, like the 16, 8, you're really not going to be getting to the point where you're activating those programs the more consistent that you can be with any longevity intervention and this earlier that you can start it, the more it's going to work. We see that all the time in the animal longevity models we're looking at.

jeff_1_09-18-2024_110403: 29:26

And I think you've answered this a little bit already, or at least alluded to it, but can fasting or fasting mimicking diets, play a role in preventing age related diseases? And if so, how, and really more specifically, how do the fasting mimics, mimetics, actually have an advantage in preventing age related diseases? And that's probably really the question I'm asking since you've already kind of answered the first question.

dr--chris-rhodes_1_09-18-2024_110403: 29:49

just to recap what we said before the activation of beneficial cellular effects especially on the metabolic side, fasting can really help to prevent. Treat or delay age related diseases like cardiovascular disease cancer autoimmune diseases and neurodegenerative diseases. it's a multifaceted process, Because you're decreasing chronic inflammation, helping to decrease senescent cell formation, activating autophagy, creating better nutrient sensing pathways, you're creating, you have less typical calories overall. Right. So you are also helping to prevent cardiovascular disease You're just putting your body in more of this. cellular survival, metabolic efficiency, and maintenance mode that helps keep it protected from all the damage that it's going to be encountering just on the day to day basis. And as you project that out over years, you get this big separation of someone who is, not fasting versus someone who is fasting, when our body is in this chronic fed state, you have this chronic activation of the immune system and these growth pathways and these growth hormones that can lead to, you know, chronic inflammation, cancer cell formation, just a lot of things going wrong in the body because it's not focused on rest maintenance and repair, We got to get all this stuff broken down. We got to get stored. We got to be focusing on that rather than the maintenance of our own cells. how the fasting mimetic and how mimeo really helps to recreate that. is from a fundamental molecular level, right? So by taking the same molecules that the body would ordinarily produce during a fast and really only produced during a fast and giving them back to people, we're helping to activate these same fasting pathways that would not ordinarily be activated, We're just constantly eating our normal diets. So going back to kind of that, you know, typical Western diet of three meals a day plus snacks, we're always overwhelming our system with food it takes around 4 to 6 hours after a meal to exit the postprandial response and get back to homeostasis if you think about, eating at nine, then noon, then three for your snack, then eating at, you know, six or seven for your dinner, never actually exiting the postprandial state really at any point throughout the day. your body's always, taking in food and having to deal with it on a metabolic basis. So it never has the time to activate the fasting pathways that would be more pro survival and less. Pro, growth and replication. supplementing with those fasting metabolites helps to create a counterbalance your fed pathways are still going to be stimulated, but then you're also going to be stimulating your fasting pathways at the same time, which can help yourselves kind of multitask right? Like they're still going to be dealing with the, They're still going to be dealing with all the metabolic things that it has to deal with, but then it's also going to be activating the same like regenerative pathways at the same time. So helping to balance out that typical western diet that we're most likely going to be experiencing while also helping to activate those similar fasting pathways.

jeff_1_09-18-2024_110403: 33:01

how does one use Mimeo Health? Is it like an indefinite daily supplement or is it something that's more periodic where you go through cycles of it in terms of its application? Yeah, well, we, we typically recommend to take two every day as like an indefinite thing. the more consistent you can be with any longevity intervention, the best that's going to work. And that's what we've seen from our data so far. we got the 96 percent lifespan extension through lifelong supplementation with the MIMEO formula. the, biological age reduction we saw in humans. Was also from eight weeks of consistent use. we haven't seen any downside to consistent use and we haven't seen any benefit to cycling most of the experiments and clinical studies done with the individual metabolites themselves have also been, consistent use for anywhere between eight weeks to six months And that's where you see the significant benefits. are there any concerns for side effects or risk of long term use?

dr--chris-rhodes_1_09-18-2024_110403: 34:00

No, for these ones, it's really interesting, right? These are all natural human metabolites that the body would produce on its own. They would just normally only produce them during a fast. So your body, doesn't really get adapted to them because there's no baseline level that they would normally be experiencing So, there's no huge risk of, adaptation or dependency over time. You can go off them whenever your body's not going to care and they're all safe. they evolved within the human body. So your body knows exactly how to deal with them, how to metabolize them, how to break them down, how to utilize them without any issues. the one thing that might pop up though, and this is from an individual to individual basis. Some folks do have a genetic sensitivity. to niacin metabolism. if they do, they could experience some, GI discomfort when taking mimeo. usually that can be alleviated by taking mimeo alongside food, especially something like a dairy product, because, there's a specific, extracellular matrix that can help to bind the nicotinamide that exists in things like dairy and yogurt. that can smooth that digestive process or another solution that we have, mimeo, a daily dose is two capsules per day and we've seen folks, take one capsule in the morning, one capsule in the afternoon to kind of break up the nicotinamide load.

jeff_1_09-18-2024_110403: 35:23

So what would my daily diet look like as I'm on Mimeo Health? Do I eat normally? And is there an impact of, you know, you have somebody says, well, I'm taking this, I can just eat whatever crap I want to eat and I'm going to eat it.

dr--chris-rhodes_1_09-18-2024_110403: 35:36

That's definitely, you know, not what we advocate, right? We're definitely not. Okay, cool. You know, you've been on a, plant based vegan diet for the last five years, but you finally find Mimeo and you're like, all right, great. I can eat cheeseburgers and doughnuts and I'll be totally fine. we never say that, we can't guarantee that we'll make anybody. healthy. But we can guarantee that we'll make people healthier. whatever you are doing, I believe that Mimeo will help with it, but that doesn't mean that we're gonna get you over the line if your diet is already crap to begin with. you can take mimeo alongside your regular diet, whatever you're already doing. It will give you benefits. Absolutely. and then you can do this with fasting as well. if you are doing something like intermittent fasting, mimeo can be a really big help because. It was designed to mimic the effects of a 36 hour fast, so it can really help to your fasting benefits of your shorter fast, you know, give you those longer term 36 hour benefits, like the autophagy, like the anti inflammatory effects, like the cellular protective effects that you might not otherwise experience in your shorter fast, but it also can help make those shorter term fasts more effective. Easier because the OEA that's in MIMEO has great effects on appetite suppression and, hunger. And the PEA that's in MIMEO has great effects on energy enhancement, cognition and mood enhancement, and also pain relief So it makes the process of fasting a lot easier. We've had a lot of customers come to us and basically tell us that I've never been able to fast this long before. You know, I don't feel hungry throughout the day and I can just kind of get through it without all that. food noise great for enhancing a fast.

jeff_1_09-18-2024_110403: 37:13

Well, it seems for weight management, it gives a bit of an appetite suppressant that can help you over the course of the day, have an overall caloric restriction to be somewhat hypo caloric if you need to be, or at least maintain that eucaloric diet to have more of that longevity effect. so I think that can be a big benefit, but what about athletes? Do you have any experience with athletes? we talked about Their health benefits, longevity benefits by eating less frequently and delaying that period before we actually break a fast. But athletes can't get away with that. I train at four 30 in the morning. and. busy throughout the day. I tend to have to break up my protein throughout the day. I have to manage my meals. I tend to do better on six meals a day as opposed to three meals a day. what experience do you have with athletes or individuals that might want to go a more high frequency diet or are, consuming a diet that is somewhat contrary to the fasting type of lifestyle, albeit a healthy lifestyle.

dr--chris-rhodes_1_09-18-2024_110403: 38:14

Yeah, great question. we've seen pretty good results with athletes so far, especially because of the effects of PEA and OEA and then spermidine to a certain degree for actually creating a beneficial exercise, like muscle performance, muscle recovery, exercise recovery effects. So PEA specifically has been shown in multiple studies to really help Reduce, like, delayed muscle soreness, help to actually improve athletic and exercise performance. The fun anecdote that we tell is that 1 of our investors who was evaluating Mimeo for our seed round wanted to take it. Before he was going to go on this big cycling Trek with his friends and he's, you know, done the course before. and he was basically in a race with a couple of other, the like VC investor friends. so he took me around a half an hour before he was going to do it and. told us he could actually feel the benefits kind of right away and set a personal record for his, for his course and beat out all of his friends. And that was one of the reasons why he ended up investing in Mimeo. We had a similar experience with another investor who was a marathon runner and basically told us like, yeah, when I was taking it, I could go farther than I really could before. And I didn't feel as, drained the next morning. So we've seen, good anecdotal evidence from our investors and customers. We've seen good clinical evidence that PEA and, the MIMEO formulation as a whole can be really helpful for enhancing exercise performance, muscle performance, and recovery as well. In terms of the frequency of eating, that won't have much of an impact on what Mimeo can give you, if you want to eat six meals a day and take Mimeo, that's fine. If you want to take three meals a day and take Mimeo, totally fine. The appetite suppression effects might actually, you know, work in your favor if you're doing six meals a day. Cause, you know, typically those smaller meals throughout the day are, I refer to them as like food teases, right? They're like smaller meals that might not be actually getting you up to the point of your hunger thresholds. and Mimeo is going to help lower that threshold. So that smaller meal is going to be a lot more satiating and easier throughout the day.

jeff_1_09-18-2024_110403: 40:25

So would you recommend somebody Fasting, you know doing a prolonged fast in addition to their habitual use of Mimeo health

dr--chris-rhodes_1_09-18-2024_110403: 40:35

I would definitely say that for people who want to do multi day fast, I think it's a good experience to have at least once in your life because it really helps empower you, to know that you don't have to always be eating, if it's lunchtime and all that's available is like pizza and cake because, someone decided to bring those things in for a birthday you can just say Oh, that's great. super happy to celebrate with y'all, but I don't need to eat it. I'll just wait until the next opportunity when there's something healthy for me, because I've gone 72 hours without fasting before or 36 hours without fasting before I can wait another three. So I definitely recommend that people do still do more of the multi day fast. If you are doing a multi day fast, Mimeo can still be helpful for you, especially because of the OEA, right? You can kind of help, to suppress appetite, especially in the beginning stages of fasting, so you can get into it a little bit easier. but if you're going to do a 48, 72, like one week, whatever it is fast, Mimeo is probably not going to add too much benefit beyond the 36 hour mark, because that's the thing that we are ultimately trying to mimic. So your body is going to be creating these molecules in those deeper stages of prolonged fasting anyway. if you want a boost to them, and get more of that appetite suppression effect or cognition enhancement or pain relief effect, then by all means, but I wouldn't say that it's necessary unless you want just a little bit of an extra kick.

jeff_1_09-18-2024_110403: 41:56

so the potential benefits for older adults, are worth considering. But what about younger individuals, particularly adolescents?

dr--chris-rhodes_1_09-18-2024_110403: 42:02

adolescence is interesting. We typically don't recommend that, anybody under 18 take mimeo not because there's anything inherently unsafe about the molecules or that we have any data to show that, but it's more that the data doesn't exist. And so we don't feel comfortable making the scientific claims around it. in that same vein, we don't feel comfortable making those, claims or taking any kind of risk with people who are pregnant or breastfeeding just because the science isn't there. in terms of, how it's going to, you know, affect younger folks, it's going to affect younger folks at a probably more subtle level. I think you'll still get the appetite suppression effects. You'll still get the cognition enhancement effects. One of the recent studies with PEA was with Younger college students and showed that, you know, eight weeks of supplementation was able to enhance their memory and their focus and their levels of cognition, without changing anything else, just supplementation with so it can definitely still be helpful there. you're going to get very similar benefits as you would see in an older population, but I think that older population is going to be able to feel it a bit more than a younger population, right? Because there's more things that could be going wrong.

jeff_1_09-18-2024_110403: 43:15

Okay. And you mentioned earlier before we got on the air, just recently being on the Ben Greenfield podcast. And I think it was that podcast where I heard, talking about, some of the immediate reproductive effects of fasting. And it got me thinking, I don't know if you're familiar with the study that was done in Sweden on the overcallings, population.

dr--chris-rhodes_1_09-18-2024_110403: 43:37

Dutch hunger

jeff_1_09-18-2024_110403: 43:38

yeah, where they looked at, both men and women during their pubescent periods, and the sperm would be developing in the males and the eggs were developing in the females. they saw that there was this kind of epigenetic effect that was lasting into their grandchildren. I think it was if the grandfather was. going through puberty during a period when he was, in a fasted state or kind of, you know,

dr--chris-rhodes_1_09-18-2024_110403: 44:03

Yeah.

jeff_1_09-18-2024_110403: 44:04

that he ended up having male offspring or grandchildren that would have a shorter lifespan. And then for females, it was the opposite.

dr--chris-rhodes_1_09-18-2024_110403: 44:11

yeah, they were more prone to, metabolic disorders, type 2 diabetes and cardiovascular disease. And that's really, really interesting, right? And of course, it would be in the men and not in the women because the women have the two X chromosomes. So there's like one healthy one, right? And then, for the men, it would be like, okay, cool. we're getting the Y chromosome and that's super unhealthy. there's only 1 copy. so that makes total sense, from a reproductive aspect from an epigenetic aspect. really interesting to think about. essentially, it's what we were talking about before, right? you can see. How the metabolic state of the parent ends up, affecting the metabolic state of the child. from an evolutionary perspective, from an epigenetic perspective, what you were seeing was that the father was in a nutrient poor environment, the sperm epigenetics, switched around to try and give the offspring a metabolic advantage, So, their metabolism of the child is gonna be a lot more efficient, than that of the parent because it's this genetic signal like, Oh, this kid is gonna be coming into an environment that Doesn't have a lot of resources. So we're going to make sure that we're trying to maximize as much of these metabolic efficiency pathways as we possibly can, but then taking that child who ultimately will need a lot less calories to survive than a typical person that wasn't raised in famine. And then putting them into an environment that is the one that we experience on a day to day basis, like in not war time, where you can have all this food available to you at any given point, that's going to end up probably creating these metabolic health disorders like obesity cardiovascular disease and type 2 diabetes, because the average that they're going to get on a day to day basis is going to be way more than they need. So they're kind of going to chronically be overfed.

jeff_1_09-18-2024_110403: 46:00

So he really kind of brings in an interesting long term line of study with, any of this research that's being done with the fasting mimicking diets or the, fasting mimetics the impact of having a more stable metabolism now, what impact that's going to have on our future generations and how that's going to impact their ability to manage with whatever kind of diet comes along.

dr--chris-rhodes_1_09-18-2024_110403: 46:25

I

jeff_1_09-18-2024_110403: 46:25

just thinking about how, you know, by stabilizing that diet, where, kind of setting up future generations for maybe being a little bit more protected from the extremes of the diets we might be getting. Is that making any sense from your perspective? I'm a different kind of PhD than you.

dr--chris-rhodes_1_09-18-2024_110403: 46:46

I think the Dutch hunger study is a perfect example of intergenerational trauma, Trauma being passed down from one generation to the next. even, you know, beyond a psychological basis, but into an actual like ever genetic and genetic basis and that's incredibly interesting. I think that's a fair theory to have, that the metabolic state of the parent is going to have some kind of impact on the metabolic state of the child and how they're going to be able to process food. And I wonder if it can go in the same direction, or in the opposite direction, right? If we reduce calories and we fast, while we're also procreating, you're going to have a progeny that's, much more metabolically efficient. I wonder if we can also create progeny that are much more metabolically inefficient, right? So basically, they would have really fast metabolisms because they're getting that signal that. There's plenty of food. You don't have to worry about it. So let's actually rev up the metabolism so that we can eat more and still be fine. we see that across the genetic pool all the time, right? Everybody has that friend where it's like, Oh, they can eat anything and they're super skinny. And then we have the people who was like, if I even look at an Oreo, I gained five pounds.

jeff_1_09-18-2024_110403: 47:54

how does one's daily diet interact with the fasting protocols to optimize short term health benefits and long term aging outcomes?

dr--chris-rhodes_1_09-18-2024_110403: 48:04

Right. the advice for someone who's fasting is going to be the same as the advice for someone who's eating normally, You want to get really good quality nutrition. You want to get, plants, vegetables. you want to get the bioactive from herbs and spices. You want to make sure that you're optimizing your macronutrients. You want to make sure that you're getting enough micronutrients. You want to make sure that you're getting enough, fiber. No matter where that's coming from or how you're actually like, you know, at what time of day, you're consuming those things, it can be a little bit harder for fasters, Because you have a lot of nutrients that you got to get into your body and a lot of bioactive molecules that you want to get into your body in a shorter eating window. And, you know, that's part of the benefit, right? That's why it works for weight loss. It's also harder for the actual, nutrient density. So you really want to focus on foods that do provide a lot of nutrient density. So that's going to be things like, fruits and vegetables and lean sources of proteins while minimizing things that are more calorically dense and less nutrient dense. So things, like white carbohydrates, rice flour, even potatoes, although potatoes are very satiating, but that's also not what you want in an intermittent fasting, lifestyle. that's what I would say I tend to eat, I do one meal a day. Still my mimeo because that's what I found worked for my lifestyle. I really like being able to wake up in the morning, have a cup of green tea, have my two mimeo, and then focus on the busy lifestyle of a biotech. Startup CEO, at the end of the day, I kind of get to, you know, put work aside. And then it's just like, Oh, my one big meal. It's kind of like, you know, a vacation meal almost where I get to, you know, decompress from the day and then kind of wind down. And what I'll do for that is stick more to the paleo principles. And not because I necessarily believe in the evolutionary, like, aspects of the paleo diet, but because it is maximizing micronutrient and, you know, bioactive and macronutrient density while minimizing caloric density. So I get everything I need in, that one meal

jeff_1_09-18-2024_110403: 50:08

Okay, I'm going to jump ahead to this question. this is the question we ask of all of our guests and you've started to answer it by talking about your nutritional habits But what else are you doing personally to age well?

dr--chris-rhodes_1_09-18-2024_110403: 50:21

So I definitely love going out and existing in nature, doing the, long hikes and just kind of, you know, you can call it dopamine fasting to use a trending term. I won't look at my phone. I'll just be out there in nature, taking it all in, experiencing things as, we kind of evolved to experience them, looking at the different shades of green, right? Practicing mindfulness of just being in the present, being in the moment. I also do meditation, because that's a great way to, rest, relax, and center yourself while also activating white matter and gray matter connectivity, weightlifting is a big one for me, because muscle is one of the most important aspects going into older age, and it's very determinant of people's longevity. The more muscle mass that you have after age 65, the better off you are, because one of the biggest things is frailty and sarcopenia and falls, So maintaining, muscle mass and balance as we age, very, very important. And then, I always try to get on the cold exposure train. I can never quite do it. I know that it's really good for me, but it's also the most painful thing that I can do on a daily basis. That's also good for me. And I have to have, some level of personal dignity, along with all of my other, longevity stuff. So I know, some people swear by it and they just love it. And it's like, you know, you got to break through and Love the pain. And I'm like, No, that one's not for me. But I am really interested in it from a scientific level. in the same way that we ran this process for mimeo and fasting where we decoded what was happening in the human body during a fast and find a way to recreate it. I would really love to do that with cold exposure, what are the one of the cool molecules that are being produced that are activating these Beneficial cellular stress resistance, pathways from cold exposure and then be able to activate them on demand. So, you know, in a couple of years you can look out for that product from Mimeo.

jeff_1_09-18-2024_110403: 52:14

I'll be watching for it.

dr--chris-rhodes_1_09-18-2024_110403: 52:16

Yeah.

jeff_1_09-18-2024_110403: 52:16

I can stop taking my cold showers.

dr--chris-rhodes_1_09-18-2024_110403: 52:18

Yes, finally.

jeff_1_09-18-2024_110403: 52:20

Cold plunging, I mean, they're just inconvenient. That's the hard part with it. I would love to be doing it, but I can't convince my wife to buy a cryo chamber or any of that kind of stuff. I would love to have a sauna and a cryo chamber.

dr--chris-rhodes_1_09-18-2024_110403: 52:32

And there's just something unwholesome about drawing a cold bath. I can't get my soul around it.

jeff_1_09-18-2024_110403: 52:37

what are the future innovations and research that you're most excited about, in the realm of fasting and cellular health and aging you just mentioned, being able to find a biomimic of the cryogenics, but

dr--chris-rhodes_1_09-18-2024_110403: 52:51

that's really kind of a bit of a spoiler from the last answer, but that is the thing I am most excited about. So Mimeo, our name is Mimic and Biology smushed together. that goes to our biomimetic approach, which is really biology. Looking at the human body in these interesting regenerative states like fasting exercise sleep meditation and cold exposure and really teasing out what's going on in the body that's activating these beneficial effects from all of those interesting regenerative states and finding a way to recreate them on demand. And so that's really what our back end, science is all about, even within the fasting realm, When we did our initial. clinical study, we found that there were over 300 metabolites that were significantly upregulated during a fasting state. we were able to screen through, about two dozen of those to find our four synergistic metabolites based off of literature results of being bioactive, whether that was a clinical study or what have you. Um, but that leaves us, 250 other targets. on the table that we really just don't know anything about, but are still part of this larger fasting bio program. we're currently looking at how we can screen through and incorporate more of these molecules into, the fasting pneumatic that we already have to make it bigger and better and more accurately recreate that bioprogram. Yeah, that larger bio program of fasting. so we're also doing, and I'm very, very excited about this, um, a randomized, double blind placebo controlled clinical study right now with the Mimio formulation. up with people science to do a big decentralized clinical study there, and we're looking at all the same things that we looked at before with our case study example from Mount Sinai. including the biological age, and that's really significant just in the field of healthy aging and longevity because no other supplement has done this before. No other company has done this before. You know, there are plenty of other companies who have done retrospective analysis, basically looking at. our customers and their self reported biological age data we'll be the first to show in an interventional clinical study that mimeo can actually reduce biological age in humans. And, you know, that'll be, that'll be a really significant leap forward in the field.

jeff_1_09-18-2024_110403: 55:12

it sounds exciting. there's so much exciting material in this conversation today and so much more on the horizon. So, Dr. Rhodes, how can our listeners connect with you and learn more about Mimeo Health Technologies? I know there's a website, so the website is their social media.

dr--chris-rhodes_1_09-18-2024_110403: 55:30

Yeah, social media and website are basically mimeo health. com for the website and Mimeo Health everywhere else. M I M I O health.

jeff_1_09-18-2024_110403: 55:40

So you got to emphasize the second I in there because it's easy to say Mimio. Great. Well, this has been a truly enlightening conversation. I really appreciate your time today. I've learned a lot. thank you for joining us and keep doing what you're doing and keep aging well.

dr--chris-rhodes_1_09-18-2024_110403: 55:54

absolutely. Thanks so much for having me.