Jay Feldman 00:12
Welcome to episode 23 of the energy balance Podcast. I'm Jay Feldman. I'm a health coach and independent researcher, and joining me again today is my good friend Mike Fave. Mike and I have been studying health and nutrition together for quite a while now, and Mike also draws on his experience from working within the healthcare industry. Today's episode is part one of a two part series talking about how to slow aging, and in today's episode in particular, we're going to be going through the different theories of aging, and we're going to explain kind of how they differ and how to reconcile their differences. And we'll also be talking about the larger picture, as far as why increasing our metabolism is the primary thing we want to do in order to slow down aging and extend lifespan. We'll also be digging into why the polyunsaturated fats oppose health and shorten our lifespans and increase aging. We'll be talking about the role of free radicals and oxidative stress in aging. And then we'll be talking also about the state of aging and lifespan research, where a lot of the issues are and how this leads to recommendations that are not always accurate. Throughout today's episode, we will be digging into the biochemistry a little bit, especially for about 15 minutes in the in the middle, but I will be pulling up some diagrams to help you understand and visualize the concepts that we're talking about. So if you are listening to this episode, you may want to watch this one on YouTube, and the link to that YouTube video will be in the show notes. But even though we do get into the biochemistry a little bit, we do make an effort to summarize it and try to and try to make it easy and simple to understand. So even if you're not as interested in the more in depth scientific side of it. I do think it's worth sticking it out and listening through, because it provides a lot of context for these different theories of aging and and support for why we do want to be increasing our metabolism in order to slow down aging and extend lifespan. So to check out the YouTube video and any of the other articles or studies or anything else that we reference throughout today's episode, you can head over to the show notes at Jay Feldman wellness.com/podcast and if you are looking to reverse aging and all the other symptoms and conditions that come with it, whether that's chronic pain and joint pain, or weight gain or gut issues or constant hunger or hormonal imbalances, a lack of energy and fatigue, if you're not sleeping well, then head over to Jay Feldman wellness.com/energy, and sign up for free energy balance mini course where I'll walk you through the main things that you'll want to do to support energy production and the things that you want to avoid that cause the wasting of energy. And by doing these things, you'll put your body in a position where it has the most energy available, which, as we'll talk about throughout today's episode, is really the key to stopping and reversing aging, extending lifespan, and also preventing and reversing all sorts of different health symptoms and conditions that so many people are experiencing all the time. And with that, let's get started. So there are a lot of competing theories as far as aging and lifespan go. And we obviously talk a lot about increasing energy production, increasing thyroid function and the reproductive hormones, and producing more energy and also using more energy. And many people would say, or do say that this should cause us to age faster and decrease our lifespan. And a lot of that is coming from this very outdated theory of aging called the rate of living theory, where, and again, this is very it's very common in like, colloquial use, where people will talk about, kind of the idea that if you live like, live fast and die young, or burning the candle at both ends, or you'll hear it a lot, also just talking about, you know, that we have a fixed number of heartbeats or fixed number of breaths, and so We want to be breathing less and using, you know, have a lower heartbeat so that, you know, so we don't die as quickly. And there's, there's all sorts of different kind of offshoots of this, and this is a lot of the time why people suggest doing like calorie restricting and intermittent fasting and all things like that that are supposed to lower our metabolism. And it's all coming from this, this rate of living theory, where the idea is that we it basically comes from thinking of the human body in terms of machine. And that's really where this thinking came from. It came from the time of the Industrial Revolution, where, obviously, with the machine, you only get so many. Uses before it starts to break down. And so a lot of people thought of the human body in that same way. And the good news is that's not at all the case. We aren't just machines, and instead, we are complex, adaptable organisms and and one of the biggest, I mean, a few of the differences between us and machines. I mean a we're adaptable, so we can adapt to our environment and create all the sorts of adjustments so that we can best live in that environment. But also, we have the ability to repair ourselves and regenerate, which completely throws a wrench in this whole idea of like, this whole mechanical view of of humans and of physiology, and a lot of the support for this idea of the rate of living theory came from looking at lifespan and metabolism or energy expenditure, I should say, where They basically found that the animals that lived the longest typically had the lowest energy expenditure based on their body weight and so. So just a few examples there that are kind of very common and easy to think about some of the animals, which with much lower metabolisms compared to their body rate that live a long time would be like us and other large animals, or large mammals, like whales or elephants, or like rhinos, or even like a tortoise or something, where the they you know, these are examples of animals that have a low metabolic rate relative to their size and live A long time. And on the other hand, you have like mice or rodents, or also all sorts of like kind of small mammals that have a very high metabolism or high energy expenditure relative to their size, but they don't live a long time. And so when you look at this, somebody might say, Oh, well, the more energy we expend, the quicker we die, because all these small animals with really high energy expenditures die very young, whereas we, you know, we're able to live much longer, and other long lived animals use much less energy relative to their size. But there are a lot of there. There are certain things that kind of confound this that don't, don't fit this, this narrative.

Mike 07:25
Do you want to talk specifically about the things that confound or do you want to give examples of other species that are smaller and have a higher metabolic rate, but comparative to other animals in that group have lived a long time, like bats or making mole rats or things like parrots, which are examples of those confounding variables that we're going to talk about?

Jay Feldman 07:46
Yeah, yeah. So we'll so we'll wait real quick on the confounding variables. But yeah, those are, those are exactly the example, perfect examples of animals that don't fit this narrative, where the like, the higher energy expenditure doesn't result in in a shorter lifespan. And there is a reason for that, which we will talk about. But, yeah, naked mole rats, bats and parrots are all pretty good examples. I think there are a few different bird examples that are, that are pretty good evidence here, where they live much, you know, a pretty long time, despite having size and metabolism, yeah, yeah, a very high energy expenditure. And we'll talk about that as we talk about some of these other factors that actually do affect aging and lifespan, which are not simply more energy expenditure equals shorter lifespan. So yeah. So there are these, these several exceptions to this supposed rule, and there's some other major evidence against this, which is the evidence that when they look between different species, this, this idea of high energy expenditure and shorter lifespan does tend to hold true. I mean, there are these exceptions that we mentioned, but when you look within a species, so, so if you were to take, you know, just just to look at all elephants, or just look at all humans, or just looked at all rats, for example, the ones with the higher energy expenditure or higher metabolism, which we'll have to make some clarifications there as far as what those things mean. But the ones with the higher metabolism actually live longer, which is the opposite of what's found between species. So this is these are some of the some things that just point to the fact that there are other factors involved, as opposed to just using more energy, leads to a shorter lifespan, and that's led to some other theories as far as aging goes that are kind of closer to what's accurate. Do you want to add anything to this rate of living theory before you go on?

Mike 09:37
No, we pretty much covered it. Okay, yeah.

Jay Feldman 09:41
And I do think it's important to mention as well, just how pervasive it is to where people talk about the benefits of exercise and how it allows for a lower heart rate over time, and that that's supposed to be beneficial for the same idea, like the same reasons people will talk about, again, fascinating, caloric restriction being beneficial. For the same reasons, and we'll talk about why they're not and what other variables are playing a role here. So yeah, it's even if you're not considering it, you're not thinking about what might extend lifespan or prevent aging. This is really an ingrained idea throughout our society, and especially the health and nutrition fields. But one so out, like, kind of beyond this rate of living theory, a more recent theory as far as aging goes, was the free radical theory, which then became the oxidative stress theory, which is the idea that oxidative stress in the cellular environment causes damage to the protein structure, to the DNA, that then leads to aging and eventually a shorter lifespan. And this is definitely kind of, I would say, closer to accurate, where there's there's definitely something to be said for increased oxidative stress and reactive oxygen species causing problems and that excessive amounts do lead to shorter lifespans and increased aging. But I would still say it's not quite that simple, and it doesn't necessarily it's kind of more more still on the surface, it's not as deep down as what's really leading to the aging and decreased lifespan.

Mike 11:20
This specifically in terms of, are you going to jump to here, to membrane pacemaker, directly from free radical?

Jay Feldman 11:26
Or, yeah, unless you have anything to add to the oxidative stress theory or free radical.

Mike 11:31
I mean, it's essentially just, just a production of, I guess you want to think of it as, if you're at a car, it's like the smoke produced from burning gasoline. The same sort of processes, to some extent, occur within the mitochondria when you're oxidizing different sources, whether it's fat or carbohydrate for fuel. And would that would that process, these these different compounds that are created have the ability to basically damage the surrounding structures, if not properly mitigated. The thing is, is the question which here, which can lead into the next understanding is, number one is, how do you limit the production of those, those species, the reactive oxygen species. And then the second question from there is, how do you have, how do you have structures that are less likely to be damaged by these reactive oxygen species. So you can tackle it from multiple different areas, number one or and then the third area would be being able to clean up those reactive oxygen species before they produce damage. So that theory, there is some there is some validity to the theory. It's just, there's, there's, it extends into other parts, and those other parts are mainly, how do you clean up the damage? How do you prevent the damage? And then how do you how do you prevent the damage in terms of preventing the species from being formed, and how do you prevent the damage in terms of having structures that are are relatively resistant to the oxidation of of of the structures themselves? And so then that will lead us into the next theory, which is essentially the membrane pacemaker theory before we get there.

Jay Feldman 13:02
I just wanted to mention that as far as the oxidative stress theory, one one thing that's important to note is that it is not all encompassing. As far as that sort of damage, where there's oxidative damage is not the only type of damage that occurs that we need to be concerned about, and that's part of the issue too. So you can also have reductive stress, as opposed to oxidative stress, which can cause just as many problems, and is often a problem, and another thing so and just to clarify also, you were kind of saying that you're putting context to where these reactive oxygen species come from, and I think that's helpful. So basically, just in our regular like our regular life, just the regular processes that lead to the production of energy, and usage of energy and all those things. There are these byproducts, these kind of waste products. And that's what you were getting at, like the exhaust from an engine. And there are, there's like, some damage that comes from them, but they should be in kind of a balance. But as you were alluding to, there are certain things that can create excessive amounts of these, these waste products, which, I mean, it's not quite that. It's not like waste products, exactly, but, but there are things that can cause excessive amounts of these products. There are excess things that can create more susceptibility to damage from them. And then also there are factors that help to clean them up and prevent them from causing issues. So, yeah. So with that, let's, yeah, go ahead and touch on.

Mike 14:20
Before you, before you go ahead, you can also have oxidative stress not necessarily related to metabolic like to metabolism in general. You can have certain things that you eat in your diet, or toxins or things like that that can directly induce oxidative stress in different areas, first, specifically heavy metals and things like that, lead or even accumulation of iron can create an excess of oxidative stress or high intakes of polyunsaturated fatty acids, particularly heated polyunsaturated fatty acids can create oxidative stress and damage within the bass BUTCHER So it's not only the theory. From what I understand, the theory. Three is main focus is around metabolism in general, and oxidative stress produced by metabolism. But there's also other areas where you can have oxidative stress, and those are just some basic examples that I was talking about before.

Jay Feldman 15:15
One of the one of the really common examples too is ionizing radiation, where it's acknowledged that this causes cancer and all these problems, and that's because it directly causes free radical production from this ionizing radiation. So, so that's another example of of the relevance of this.

Mike 15:33
In reference to the radiation that I think we can touch on the oxidative stress, one of the some of the main things that it damages in the cell. And this will go, this is a good bridge for the membrane pacemaker theory is, if you don't have the proper defenses available to basically get rid of the reactive oxygen, reactive oxygen species, or quench them per se, then you the damage tends to damage protein structures and specific fatty acids, and then at the at some of the higher levels DNA, which is what you see with radiation and ionizing radiation and things like that, directly causing damage to DNA.

Jay Feldman 16:12
You had mentioned that, like the connection between the oxidative stress theory and metabolism, and I think that was important connection to make, because this was basically still a sense. Still essentially born out of the rate of living theory. Or, I guess, what it more was, is an explanation for why there is this connection between energy expenditure and lifespan and aging, and why sometimes it doesn't have the effect that we would expect, but why often it does so that what they're kind of saying is that when you have higher energy expenditure, you have more accident distress. So this kind of explains why there is that general correlation there. And so yeah, I think it's just important to kind of contextualize that as is still kind of an offshoot of the rate of living theory, but, but just kind of more as far as, like, the underlying basis and what's leading to it. So yeah.

Mike 17:00
But with, even with that said, you don't just depending on how you're what you're putting through the mitochondria and construction of the mitochondria and things like that, you don't necessarily will have you. You may not necessarily have more reactive oxygen species, for example, if you're burning more carbohydrate, as opposed to burning more fatty acids or things like that, those will adjust the amount of reactive reactive oxygen species. So it's not as simple as just increased metabolism, increased reactive oxygen species. There's really like, there's there's other factors that are involved, and that goes with the membrane pacemaker theory, which essentially discusses membrane unsaturation and peroxida, peroxidizability of the membrane, which is determined by, to some extent, by the amount of polyunsaturated fatty acids, types of polyunsaturated fatty acids, ratios of polyunsaturated fatty acids, and then subsequent ability of the membrane to be peroxidized or damaged by the reactive oxygen species produced during mitochondrial respiration, and this is specifically of the membrane of the mitochondria, if I'm not mistaken. And the focus is around the membrane of the mitochondria, because if you understand cellular respiration, and what the what the electron transport chain does, if you within that theory, if you have damage to that membrane, and you allow the membrane to be porous, per se, or because of the increase of polyunsaturated fatty acids, and then the damage to those polyunsaturated fatty acids, then you essentially inhibit the ability to establish a proton gradient and then drive At ATP production. So it's important to make sure that you don't have the damaged membrane in the mitochondria, and then, essentially, when you have an extensive damage to the mitochondria and the membrane and energy production is destroyed, you get a whole that the amount of reactive oxygen species produced in that cascade and whatnot is a signal to literally destroy the cell in and of itself, and starts a whole cascade down the basically down that line with calcium release and things like that. So the next theory specifically involves looking at polyunsaturated fatty acids, their ratios and types within the mitochondrial membrane and peroxidative damage from respiration and lifespan and things like that. So it basically takes those other theories and adds a layer of nuance to them and a layer of depth to them that basically changes the the argument altogether.

Jay Feldman 19:35
Yeah, yeah. And so to to zoom out a little bit for people who are not familiar with membranes or mitochondria and peroxidation. What we're basically talking about is that the mitochondria are the part of the cells that are basically the engines that's where the energy is produced. And there's a fatty acid. There are fats inside of there, and also, and what they. Called the, what they call a phospholipid bilayer, which is the idea being that there is this layer of fat surrounding it, and that kind of, that's kind of like the this, not skin of it, but the like.

Mike 20:14
You should just pull the picture, the of the mitochondria, if you want to. You could show it's, I think it's easier to show with the diagram, yep.

Jay Feldman 20:22
So for people watching on YouTube, you'll be able to see this if you're listening, then maybe go check out the YouTube video. But I'll try to explain it so that it's clear. So I just pulled up a an image of the mitochondria. There's more on here than we need to discuss. But there are these kind of two compartments you have, like the outer and inner compartment. And there are these two, what are called membranes, the outer membrane and the inner membrane, and both of them are made up of fatty acids. It's called a phospholipid bilayer. And this is, again, there's considerable evidence against the presence of these phospholipid bilayers in the way that they're talked about, but the same principles apply where the fatty acid composition of the cellular structure still matters. So we're going to talk about it as if it is a phospholipid bilayer membrane, even if that doesn't actually exist. So along this inner membrane is where, basically the the machinery producing energy is housed. And so because of that, the fatty acid composition of this, of this membrane matters a lot, because there is a there's basically a charge. There's a there's a separation of components between the inside and outside of different ions. And specifically in this case, it's it's protons, and this creates a charge that's held based on the difference here, like an electrical charge, and this is what is supposed to lead to the generation of energy, is the maintenance of that charge. And so depending on the composition, like depending on what type of fats are contained in this layer, that affects all sorts of all sorts of factors going on here. And as Mike was saying, one of the things that affects is the susceptibility to damage. So we've talked, we did an episode talking about the polyunsaturated fats, or PUFA, and these are much more susceptible to damage. And because of that they are like when we're talking about peroxidation or oxidative stress or free radicals, that is all just kind of different forms of this damage, and the polyunsaturated fats are very susceptible to it. So when, so this, this membrane pacemaker theory is basically the theory that the types of fats in these layers is the main determinant of health and lifespan, and of lifespan and aging. And the reason for that is because when these layers are comprised more of polyunsaturated fats or less saturated fats, then they're much more susceptible to damage to that oxidative stress. And so that's what still contributes to the aging and and lifespan. And while we're looking at diagrams and things, I'm going to pull up a chart that shows just the difference in susceptibility to damage, susceptibility to peroxidation, between the different types of fats. So you can see all the way on the left we have the saturated fats, and all the way on the right we have the most polyunsaturated fats. And then the bars are showing how susceptible to damage. These are that damage is called peroxidation. So if you're looking on the left, there's non existent bars for the saturated fats, because they're very, very stable and not at all susceptible. Then you have the monounsaturated fats, which have very, very tiny bars that are almost not visible. And then you have the Omega six pollen. Saturated fats which have which are much, much more susceptible to damage.

Mike 23:46
Linoleic acid is 18 two and 24 is arachidonic, and then 18 three is linolenic, and then 22 six is doxa. It's, I think it's either EJ or DH, DHA. Yeah.

Jay Feldman 23:58
it's DHA. So for arachidonic acid, you can see this bar here. Arachidonic acid is about 160 times more susceptible to peroxidation than oleic acid, which is the 18 one right here. So this is not even looking at saturated fats. This is still compared to a monounsaturated fat, it's about 160 times more susceptible to damage, and then DHA is another is twice that, so it's 320 times more susceptible to damage than oleic acid. So the point of looking at this is just how incredibly, just how much of a difference it is between the saturation index of these fats, of how saturated they are and how susceptible it leaves them to damage, which is part of what the the main reason why the from the membrane pacemaker theory. They're saying that this makes such a huge difference in that it's the main determinant of aging and lifespan. And then I'll show I'm going to pull up a graph here that's looking at the, what's called the peroxidation index, how saturated these membranes are, and the how saturated the membranes are and lifespan. Yeah. So when you look at the at the bottom here the x axis, you have maximum lifespan, and to the right, the is longer lifespan. To the left is shorter lifespan. And on the left you have peroxidation index, where on the bottom it's less proxy, like the peroxidation index is lower, meaning there's less it's more saturated, it's less unsaturated, and then towards the top, it's more unsaturated and less saturated. And so we see this in both skeletal muscle and liver mitochondria. And it's just, I mean, it's a very clear correlation here between showing that lifespan increases as the saturation index as the peroxidation index decreases. So basically, more saturation leads to leads to a longer lifespan. And so that's, that's, again, just it. It's an explanation for why. It's an alternative explanation for why we see these differences in energy expenditure and life span. And it's kind of an alternative explanation that fits better than you know, like you don't have these outliers like the naked mole rat, for example. So we talked earlier about how when you look at just energy expenditure and lifespan, the naked mole rat is an outlier where it doesn't really fit that curve at all, but it fits this very clearly. So, so it's just an example.

Mike 26:18
Before you click off just And just to clarify, peroxidation index is basically saying how likely it is for those fats or those that that phospholipid to be damaged by oxidation. And so the higher scale you have means you have more unsaturated fatty acids, because they are more likely to be damaged by peroxidation than the saturated fatty acids. And so the other thing I wanted to point out, too is this curve I think help, will help when you look in like in group comparisons of different species, whereas before, what I think you touched on it earlier, that in in group species, the the members of those species that have higher metabolisms actually lived longer than the species species, the in the in group species that had lower metabolism that's looking within one particular species, not comparing the species, they'll be looking at just elephants. So the elephants with the higher metabolisms live longer than the ones with the lower metabolisms.

Jay Feldman 27:22
Right? Which is huge. I mean, it directly flies in the face of the whole idea that higher energy expenditure leads to shorter lifespan. I mean, it's direct evidence against it, yeah.

Mike 27:32
And so now we'll just, just to clarify some of the because it ties in nicely with the things that we're going to talk about going forward, just to clarify some of the like, well, I guess we could start with peroxidation index. So if you want to pull up the different fatty acids, there we go. So with the different fatty acids, you can see, on each group of fatty acid, there's a there's a, what's it a phosphate group. And then following that, you have the the carbon tail, or the carbon chain. And so each, each sort of, I guess, vertice vertex in the lines there represents a bond of a carbon. And then where you see, in the saturated side, all of the tails of the fatty acid are straight, right? So for lauric acid, myristic acid, palmitic acid and stearic acid, the the tails, the little zigzags following the the O, H and the O groups, are all straight so and they don't have any of the extra line that you can see on the unsaturated side. And you can see at each double line portion on the unsaturated side there's a kink in the tail or a bend. So basically, what's that showing is, in the saturated side, there's no double bond, and the double bond is indicated by that kink in the tail with the double line. And so what happens there is, at each vertex there's a carbon, and when you have the double bond there, the other lines there, it means a carbon is bonded. Is double bonded to a carbon. So it has a different interaction between the carbons. They're they're connected to each other in a different way than you would see in the saturated fats. And so what this does is it causes the tail of the fat to bend. And so as you get more of these double bonds, you get a more bent tail. And so this increase in bends means that the fatty acids can't stack up closer to each other, which creates a more fluid structure. And so the So besides the increase in fluid structure. And this is why, this is the explanation for why things like olive oil, which you can see on the top of the unsaturated list, there's oleic acid, which is C 18, and it's monounsaturated, which means it has one double bond. It only has one unsaturated portion in the tail. Why? It this, this fat here because it has, uh, the kink in the tail. It can't stack up nicely like a lower like a stearic acid or palmitic acid. And that shows why olive oil at room temperature, which is mostly a lake acid, is liquid, whereas stearic acid at room temperature, which is what you find in beef tallow or promitic acid, which is what you find in butter is actually solid, more solid at room temperature. So these same things happen in the body as well. And so the other, the other issue besides the fluidity. So in regards to the fluidity, a lot of a lot of research basically stems from the fact that an increased fluidity in the cell membrane and the mitochondrial membrane allows for more movement and increased transport and things like that at the in the cell. So, but the problem is, is every time you have an increase in those double bonds, and so here's here's an I, here's an example of the fluidity of the cell membranes. So in the left you have basically at the the little balls on top of the two legs there, that's a phosphate group. And then down below are fatty acids. And so basically the fatty acids interact with each other, because like is with like. And then the phosphate group, which is more attracted to water, because it holds charges and things like that, it's facing outward. And so this is the cell membrane, which they call a lipid bilayer, because there's two layers of lipids. And so on the left side, you see the fluid membrane, and the fluid membrane, the kinks in the tail, mean that the fatty acids can't stack so nicely as in the viscous membrane. And so part of the theories behind behind different cellular functioning is saying that with this increase in fluidity here, you basically the membrane allows more things to pass through, or like sugar and things like that. And then the cells aren't so stiff. There's like, there's ideas around around that. But the problem is, is that each one of those kinks where you have a double bond, those fatty acids are more likely to be affected by oxidating compounds. And so what happens is those oxidating compounds can interact at the sites of the double bonds and damage the fatty acids and produce these little breaks in little pieces of the fatty acids, and also allow this membrane here on the fluid side to become more permeable. And so when the membrane becomes more permeable, it has a direct negative effect. So if we go back to the to the mitochondrial picture, in the mitochondria, when you have damage to that membrane, so you have the lip, double lipid bilayer membrane there you can see with the little ball and the two tails coming down when you make this membrane more permeable, right from damage, from peroxidation and things like that, the little h plus balls can then go back through the back through the membrane. When that happens, you can't wet. So these little proteins on the left hand side here, that just look like long blobs are actively pumping out or pushing out the H plus ions. And what happens is they're creating a gradient. They're creating a ton of H plus ions on the other side of the membrane. And when that they build up this big sort of, I guess, flask looking membrane protein here is letting these H plus ions come back into the cell. And as the H plus ions come back into the cell, it drives the production of ADP and a phosphate group to turn into ATP, which you can see all the way on the right hand side there. And so when this, yeah, exactly, there you go. So when you ruin this membrane here, these H plus ions can then move across the membrane without going through this big enzyme here that's turning ATP and a phosphate group to ATP. This enzyme here is called ATPase, or ATP synthase, and so when this, when you don't allow ATP synthase to work, you can't produce ATP, which, in current theory or current understanding, is the main energy source of the cell. And so when you have a destruction of this and a destruction of the production of ATP, you have a complete breakdown of cellular energy production. And once you once you start to lose cellular energy production along this same model, or along the same theory that we're currently seeing you lose the ability to maintain the different gradients in the cell of like things like the sodium potassium pump, or different structural proteins that require energy within the cell and function along the cytoskeleton, or the ability to undergo DNA translation and transcription, and things like that, which all require ATP and energy to function properly. So basically all without this energy, the which and ATP is essentially the cellular currency. Without that cellular currency, all transactions, all functions of the cell, begin to break down. And so the membrane pacemaker theory basically. Says, when you have an increase in unsaturation in this membrane, and you you basically have the mitochondria, because right here, this is all the mitochondria. You can see inner mitochondrial membrane here, when you have a breakdown of this, then you have a breakdown of energy production. And when you have a breakdown of energy production, you have a breakdown of other things in the cell, because everything's dependent upon energy production, and then essentially, from there you lose, you basically start to degrade, or you start to die, per se. And that's why you have the idea of the pacemaker. Whereas the more unsaturated you have, or the less saturation you have, you start to the pacemaker starts to slow down, or the lifespan starts to decrease. And so the theory functions there. I know we went through a lot of biochemistry there, but I think it's helpful to see, to see how everything works. I mean, if the easy way that I remember it is the the mitochondrial membrane is sort of like, I don't know, like a brick wall, and it needs to be water tight, because you're gonna, you're pumping water out of this brick, struck out of this structure, and then you want it to be water tight, because you're then allowing that water to come back in to drive a water wheel. And the water wheel produces electricity. That's the easy way that I understand it basically like a big water mill or something like that. And so when you have, when you allow water into the into the water mill, you basically can't create. You can't the water is not going to rush in as fast to drive the wheel anymore. And that's essentially what you're seeing here in this picture. Um, as if you have a destruction in that, that inner mitochondrial membrane, or the membranes in general.

Jay Feldman 36:35
Yeah, yeah. So I'm going to summarize real quick, because that was a lot, and some people aren't watching, and also a lot of it's probably over people's heads. But so there are a few main things to consider here with the like membrane pacemaker theory and how the different fatty acids affect all these different components of energy production and oxidative damage. So Mike already explained, he explained how, when we have the more unsaturated fats, it's more susceptible to damage due to those double bonds. And just to mention, again, from the biochemistry side, the reason why they're called saturated or unsaturated has to do with the amount of hydrogens on there. So when it's a saturated fat, it is fully saturated with hydrogens, whereas when it's unsaturated, that means that there are double bonds because it is not fully saturated with hydrogens. You're removing hydrogens when you have those double bonds.

Mike 37:25
So presence of a double bond means that there's less areas for the carbons to bond to hydrogen, so it's unsaturated with hydrogen, and the more CO the more double bonds you have, the less hydrogen the carbons can be saturated with. And that's why they're called monounsaturated or polyunsaturated. And the more double bonds, the more likely they are to be attacked by oxidative speed or reactive oxidative species. And the more double bonds, the more fluid they are. Yeah,

Jay Feldman 37:53
Yeah. So that's kind of part one is those the membranes, when they're more, when there's more in saturation, they're more directly susceptible to damage. Part two is, is what we have with this diagram that's up right now, which is how efficiently we can produce energy. So from this kind of mainstream view of energy production, you have this gradient where you have less of these protons inside, a lot more of them outside, and that allows that kind of movement of the of those protons out allows for the energy required, the charge required to then bring them back in and use that energy to produce ATP. And so the point being that when the membrane is less saturated, then you have more flow of the protons, not through the complexes of the electron transport chain, not in the way that they're supposed to but instead, supposed to, but instead, directly through the membrane. It leaks through. It was more leaky, or called more permeable. So what you basically have is this leaking of energy, this leaking of charge, this leaking of its potential energy. It hasn't been used to create ATP yet, but you have this leaking of potential energy so you aren't as efficient with the energy production. So if you're using the same amount of fuel, you're going to end up with less energy. So that's kind of part two of the membrane pacemaker theory. And then the last one, which is not on this diagram, but in addition to a proton gradient here, there's also different gradients between other ions, like sodium and potassium, and so you also have increased flow of those just directly through these bilayers. And that also leads to a wasting of energy, in a way where it essentially requires energy to keep those in the same place. So when you have a lot of flow or permeability to those ions, in this case, minerals, you you end up losing energy. In that way, it's like a wasting of energy. So those are the three main issues that come about from having more unsaturated fats here, and to clarify, there's there's other views of the cell that don't require these membranes, but the same principles still apply where having more of the saturated fats allows for us to hold on to the cell, to hold on to that energy better, as opposed to basically leaking out that charge that still holds true and it. Same Damage Component still holds true in the same wasting of energy, because you're just looking at it on the on the larger cellular level, where you're holding less energy, it leads to, it disrupts the proton gradients and the ion gradients in the same way it just isn't through a lipid bilayer. There's some differences, but the same principles still apply. So I think that if you want to add anything, go ahead, but that's kind of the general summary of membrane pacemaker theory, where the the basically the more on saturation leads to more damage, less efficient energy production, and the weight, direct wasting of energy, and that all of these things contribute to an increase in aging and a decrease in life.

Mike 40:43
Decrease in lifespan. Yep. No, I don't have anything to add. I think we belabor the point now.

Jay Feldman 40:47
Yeah, yeah, which I think was still helpful for people.

Mike 40:50
No, I think it's very it's important. Yeah. And so do you want to so now we're, I guess we'll get into the Byron bioenergetic view. And then, which does play? The the bioenergetic view does incorporate the idea of oxidative stress theory and membrane pacemaker theory at to sort of basically discount, to some extent, the rate of living theory. And then from there we'll go, and we'll talk about some other areas that of after we go through the bioenergetic theory of getting that basically eliminate the idea of the rate of living theory and things like that. So you want to do the bio energetic theory.

Jay Feldman 41:28
Yeah. So the basic idea here is that rather than less wanting to have less energy, and that having less energy leads to a longer life, it's actually the direct the idea here is that it's the direct opposite, more energy equals more life, slower aging, longer lifespan. And the idea behind this does, in many ways, rest on what I was talking about in the beginning, where, which shows how different we are from machines, where, for one, we don't have a finite amount of energy reserves or anything like that, because we are constantly interacting with our environment in a way that dictates how much energy we'll have available. The other parts are that we can adapt and then also we can regenerate and repair. And so the essence here is that when we have more energy for adaptability and more energy for regeneration and repair, that this leads to longer lifespan and slower aging. And again, some of the important evidence corroborating This is the evidence looking at the how an increase in metabolism within species leads to a longer lifespan and slower aging. And that's really important. The reason why this between species versus within species is so important is because the assumption here is that the peroxidation index is the same within a species. And that's not always the case, because it's affected by diet. There are certain there are certain confines with just between different species, and then there's also certain confines within diet, but in general, within the same species, you're gonna have around the same proximation index. And so the fact that when that is equal, the higher metabolism leads to a longer life is is important. It means there's other factors going on here and that aren't just explained by the peroxidation index. And so that's kind of what we'll talk about. But again, the general idea is more energy equals more life. More life energy more ability to repair and regenerate and and we talked about this a lot in episode one of the energy balance podcast, so I'll recommend taking a look at that. But one important distinction to make is this difference between energy expenditure and metabolism, or energy expenditure and having more energy. So when we're talking about more energy, we're not saying we're not talking about exercising a ton, where you're using a ton of energy, or like towards these outside stressors or increasing stress to use more energy, and that that's going to increase lifespan and not not that the opposite is true either. But there's important distinction to be made here, as far as like, what energy actually is and where it's being used. Where, to clarify, we take in food, among other things, nutrients and things, we convert that to usable energy in the body, which we normally call ATP. In reality, it's, it's not just held in that molecule. It's, it's, as we talked about with this alternative view of the cell, it's kind of this energy, this energetic charge, is donated to the the protein structure of the cell, and that leads to increased structure, especially of the water. And that leads to basically increased function. But basically we have this conversion from food to energy, and that energy that we have is then used for all of our energy demands. So it's used for breathing and digestion and immune function, all of the things that our body is doing all the time. And then it's also used for external energy demands, our exercise or psychological stress or mental work among you know, or an infection, all sorts of environmental stimuli that also require the usage of energy. And then whatever energy is, is basically left over. Is like an is what I consider an energy surplus, which is extra energy that we then use to repair and regenerate and increase our complete. And increase our structure, which also leads to more resilience to future stress and improved function. And so the goal here is to optimize that energy surplus, or increase that energy surplus, maximize that energy surplus. And in order to do that, we want to make sure that we're producing as much energy as possible and minimizing our energy demands that are excessive that we don't need. So what this does not mean is exercising a ton, like, like over exercising that's not going to increase the amount of energy you have available, that's going to waste excess energy and decrease our energy surplus. It also doesn't mean excess amounts of psychological stress or anything like that, and also doesn't mean caloric restricting or anything like that, because that's also going to reduce our energy supply, which ends up down regulating our ability to regenerate and to function at that higher level, by decreasing thyroid hormones and reproductive hormones and then cognitive function and digestion and immune function. So it's really the opposite of those things, where it's not that anything that that uses energy is bad, it's not that exercise is bad, but we don't. But the benefit of exercise is not that it uses energy. There are outside benefits to Exercise and Movement. So, so yeah, so the idea being that if the more that, the more of an energy surplus we have, the slower we age, the longer our lifespan. And that's why we hammer this point home so much. And it's because all, virtually all symptoms and chronic health conditions that we think of are really a representation of aging. That's why they all increase as people get older, and in the same way that having that surplus energy helps to reduce those symptoms and conditions, it also literally reduces the aging that's going on. And for people who maybe don't agree with this, they might be like yelling at, I guess, themselves, or at us right now. And so what we're going to do is we're going to talk through a lot of the supposed evidence against this. Is the supposed evidence that calorie restriction is really good for extending lifespan, and all of these other kind of hormetic factors that are supposed to cause stress and lead to longer lives in slower aging, which we would say is exactly the opposite of what we want to do. It's not the case. So let's Yeah, let's go through that and talk through the research there, what the flaws are, why it doesn't hold up, and where all what these alternative factors are that do account for these, these effects that are seen in the research. And then we'll end by talking about how we can actually go about increasing the energy surplus to slow age, slow aging and extent lifespans.

Mike 47:28
So do you want to start? We'll start with calorie restriction.

Jay Feldman 47:31
I just want to first talk about the before. Well, I want to talk about calorie restriction as the main thing. But just as a larger overview of the research on lifespan and aging. There are a lot of problems with the research. One of the general problems overall is just the type of organisms that are studied. So a lot of times this research is done on on C elegans or on Drosophila, which are flies and worms and and they these. They basically don't respond to stressors in the same way that we do. And this account this is a huge component that isn't accounted for when we're looking at lifespan. So they find often that when they do something like calorie restriction or other types of stress, when they implement those sorts of interventions with C elegans, for example, the which is a little worm, it enters a hibernation state called dour and and it's, it's basically a state where the metabolic rate is dropped drastically. And they're basically, it's, it's exactly like a you would think of with a hibernation state. And it doesn't happen just with caloric restriction. It happens with any of those hormetic things, any sort of an sort of environmental stress. And this shows because they're hibernating, it looks like they live longer. So if you're just looking at how long the animal lives, it does live longer when it's under the stress, but the reason for it is because it goes into the hibernation state, which is not actually viable. It a it doesn't signify increased health, that's for sure, and that's shown on the physiological level as well. And then B is that it doesn't even mean that it would increase lifespan in a regular environment, it would. They've suggested that this isn't actually viable outside of a lab, like yes, they can hibernate for a very long time when they're in a lab, because it's very controlled conditions. But if they were to do this in the wild, they likely wouldn't live anywhere near as long anyway. So that's just a huge factor to consider when it comes to just all of this lifespan research is is the type of organisms that are looked at. And we'll talk also just about some other things to consider, as far as mice and rats and and also Drosophila go, that are more specific to calorie restriction. So one other thing to mention, real quick, as far as the lifespan stuff goes, and also just hormesis research in general, is that a lot of it, they a lot of it is used. They're looking at very particular markers or very particular outcomes, very of certain benefit. Maybe it is lifespan, or maybe it is like a lack of cancer. Markers or some sort of oxidative stress or something. But normally, when they look at the organism as a whole, they find that even if there are benefits in certain areas there, there are drawbacks in others and harms in others. And that's something that's also important to consider when evaluating that that sort of research, and I have written a couple of very long articles talking about hermesis, so I'll link to those, and that digs much more into depth in this whole idea that stress and other and like stressful factors improve our health, which I would say is not at all the case. So I'll link to that we'll talk about in future episodes. So before we wrap up this episode, I do want to expand a little bit further on the bioenergetic view of aging and talk about the relationship between our metabolism and aging, and also the other theories of aging that we discussed. So as far as the reactive oxygen species, the oxidative stress, free radical theory of aging, the the bioenergetic view, does encompass this as a component. So when we focus on the things that increase the production of energy and the efficiency of energy production, this does a few things as far as oxidative stress and free radicals are concerned. The first is that it prevents the production of these free radicals by improving the efficiency of energy production and directly preventing their production in the electron transport chain. And then the other important component here is that the products of energy production, both the most noteworthy being ATP and carbon dioxide, are also really helpful for protecting against reactive oxygen species and their effects. So this is again, kind of a larger umbrella view that does incorporate the at least aspects of the oxidative stress theory of aging, but just take it a step further, and then the same would go for the membrane pacemaker theory, where, again, with this membrane pacemaker theory, the idea is that the increased saturation of the membranes and the lower peroxidation index leads to slower aging and extended lifespan by reducing the production of reactive oxygen species and reducing oxidative stress, which is definitely the case, but it also directly impacts us on the metabolic level, as far as producing energy is concerned, where, by whereas we talked about, by increasing the saturation of the membranes. This increases the efficiency of energy production, because we don't have that proton leak that we talked through, you know, with that, with that diagram, and then it also reduces the wasting of energy, which we also talked about as far as the leaking of ions. For example, the leaking of sodium and potassium ions, that basically lead to the wasting of energy as well. So again, the bioenergetic view also really incorporates this membrane pacemaker idea, where the saturation of the membrane phospholipids is incredibly important for aging and lifespan, but really that the main reason for this is because of the effects on the energetic level and our ability to produce energy and prevent damage, as opposed to solely based on the production of reactive oxygen species. And again, some of the larger pieces of evidence for this bioenergetic view of aging also has to do with the comparison of metabolism or metabolic rate between species versus within species. So again, when we look within a species, whether that's dogs or rats or humans, the typically the peroxidation index or the saturation of the the fatty acids and the phospholipids are pretty standardized, and when that's equal, when we're looking within a species, it's found that the higher levels of energy production, and this is specifically increases in the resting metabolic rate, not the not The external energy demand, it's not the extra energy expenditure, but the resting metabolic rate. So higher levels of energy production, which again, is signified through this resting metabolic rate, has been shown to lead to longer lifespans and slower aging within a single species. So again, this, this is why this kind of shows why the membrane pacemaker theory is somewhat incomplete, because there's still variation in lifespan and aging when the saturation of these membranes is standardized or is equal so and when this is the case, the other factors that drive metabolism are the ones that determine lifespan and aging. So in this case, again, the things that will support energy production will lead to a longer lifespan and slower aging. And we'll be talking about all those things in the next episode, in part two, and and then vice versa. So even if, even even if the fatty acid saturation is standardized. Test, these other components still have an effect on aging and lifespan, and then that also brings us to one of the last pieces of evidence, or things to consider, which is just the the tight ties and correlation between mitochondrial function, or more specifically, mitochondrial dysfunction and virtually all diseases, chronic diseases and symptoms and all sorts of issues, as well as aging itself. And so there are pretty strong ties there in associations, which, again, just of course, that does increase oxidative stress. So so this does kind of play into the oxidative stress theory of aging, but in reality, the kind of the larger component here that does determine the production of reactive oxygen species and our ability to be protected against them is the availability, the availability of energy and the efficiency of energy production. And so that does supersede the saturation of the of the fatty acids, and then also just the general reactive oxygen species production. It's basically the the the larger view here that encompasses those other things, as well as all of the other factors that affect our metabolism and affect energy production, which we'll be talking about in part two. So I'll leave it there. And then part two, we're going to dive a little deeper into the research regarding caloric restriction and why this is not a viable option or a good idea for slowing aging and extending lifespan, and kind of what the issues are with the research as far as caloric restriction goes. And then we're going to talk a lot about what we should be doing to slow aging and extend lifespan, and this includes types of foods and supplements and exercise and some of the issues with some of the commonly recommended ones, and what we should be doing instead. So make sure to stay tuned for part two. If you did enjoy today's episode, please leave a review like comment a five star rating on iTunes. I'd really appreciate it. It does a lot to help support the show and let me know in the comments. Also, if you guys did enjoy having the diagrams there to help depict or visualize some of the concepts that we were discussing. To check out the show notes for today's episode, head over to Jay Feldman wellness.com/podcast where I'll be linking to articles and studies and other things that we discussed throughout today's episode. And if you are looking to do things to slow aging, extend your lifespan and optimize your health, or if you're dealing with particular symptoms, whether that's hormonal dysregulation or weight gain or gut issues or extensive amounts of hunger or chronic joint pain or lack of energy, or if you're not sleeping well, head over to Jay Feldman wellness.com/energy, and sign up for a free energy balance mini course where I'll walk you through the main things you want to focus on as far as nutrition and lifestyle are concerned, which will help to reverse these processes and also slow aging and extend lifespan. So to check out that free energy balance mini course, head over to Jay Feldman wellness.com/energy, and I will see you in the next episode.