Improve Energy & Longevity by Optimizing Mitochondria | Dr. Martin Picard

What's the deal? Can people reverse the graying of their hair by reducing their stress? Can people accelerate the graying of their hair by stressing more? Likely both are true. Yes. Okay. And I think what we discovered is that hair graying, at least temporarily, is reversible. This was surprising because it goes against this notion that aging is a linear, you know, uh, process that just happens over time no matter what you do. And here we should know actually a a hallmark of aging which is you know depigmentation losing color and your beard and your hair um is something that happens to almost everyone but at different you know stages of life and and so on and then on the same person and the reason we got into this was that this felt like the perfect experiment. Every hair has the same genome. They're all genetically identical twins, right? And they're all exposed to the same exercise regime, the same food, the same stress levels. Uh but yet some hairs go gray when you're like late 30s and then some hairs go gray when you're like in your 80s. What the hell's happening? If we could figure this out, maybe we can understand why different people age at different rates. Mhm. Uh because it's very clear that there's no more than 10% of how long you live that genetically driven. Like the best studies put this at around 7%. 7% of of longevity is genetically inherited maybe and then about 90% is not. Welcome to the Huberman Lab podcast where we discuss science and science-based tools [music] for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at Stanford School of Medicine. My guest today is Dr. Martin Peard. Dr. Martin Peard is a professor of behavioral medicine at Columbia University. He is also a leading expert on how your daily behaviors and your mode of thinking, meaning your psychology, change energy production in your cells and can accelerate or reverse biological aging. Most people have heard of mitochondria as the energy producing organels within their cells. And of course, that's linked to what we call metabolism and metabolic health. And of course, most people understand that eating properly, exercising, and sleep are critical for metabolic health. But it turns out that's only part of the story. As Dr. Bicard explains, "Mychondria don't just make energy. They act as sort of antennas to link your psychological experiences to your organ health, your rate of aging, and your sense of vigor, meaning your mental and physical readiness." He explains that how well your mitochondria work in different organs and brain areas reflects what specific forms of exercise you do, as well as how you think and how you manage stress. Today he explains the things that you can do to enhance mitochondrial function that go beyond the typical get sleep, eat right, and exercise advice. His lab has shown that aging is not linear. It's not just a progression from youth to death where your mitochondria decline over that time. At different ages and stages, mitochondrial health drops off like a cliff. But there are critical things that you can do in terms of how you eat, your mindset, and exercise that can offset those changes. His lab also famously showed that graying of hair is indeed related to stress and is also fortunately reversible. By the end of today's episode, you will not only have had a master class in mitochondria, he explains mitochondria with immense clarity so that you really will understand how these incredible organels work to produce energy and as these sort of antennas to direct that energy from outside you and by the things you do. And by the end of today's episode, you'll also have a lot of actionable items that you can apply toward your health and to offset aging. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Martin Peard. Dr. Martin Peard, welcome. Thank you. Your work is so relevant nowadays. I suppose it was relevant always, but these days we hear so much about mitochondria. Most people have perhaps heard of mitochondria, they think the powerhouse of the cell, but you're going to tell us that it's a lot more than that. And I should say right off the bat that if people think that perhaps a discussion about these little organels we call mitochondria is not for them, keep in mind Martin's laboratory was the one that discovered that you can indeed reverse the graying of your hair. Uh that graying of hair is not a prerequisite uh of aging. There's some other ways that hair grays. So we'll get to that later. Super interesting work. I have a million questions for you. Let's start off with the most important and most basic question which is what is this thing that we call energy? There's electrical energy. We know the sun gives us energy etc. But when we're talking about the energy of life physical and mental vigor, the feeling that we want to do something as opposed to have to force ourselves to do it. What is this at the organism and cellular level? I mean even physicists don't agree on what energy is and there's been debates you know Richard Fineman who was like this amazing science communicator physicist said like we don't even know what energy is and what's the best way to define it because there are all of these forms thermal energy heat right energy electromagnetic uh kinetic energy movement speed right uh potential energy so uh energy kind of manifests in all of these different ways so in in a nutshell I think the best definition I've I've heard heard uh from my wife Nosha is uh who's a biohysicist energy is the potential for change right so and that applies to any kind of form any form of energy you can think about it's the potential for change for changing something in the system and that's uh I think an accurate description of you know thermal energy if something is frozen solid there's no you know potential for for moving something we need to be at 37 7 Celsius, right? The human body it gives us the potential to move and muscles to contract and you know our biology to to to function. So this is just one example where there's like a sweet spot of energy or there needs to be some thermal energy. You need to be a little warm to be alive. Um uh so the potential for change and then it manifests in all these beautiful ways. Uh and it's something that flows. You know when a key property of of energy is something that has the ability to flow and to transform. So you can never create nor destroy energy, right? That's like a fundamental law of thermodynamics. But energy always transforms. So you can transform heat, right, into motion, right? And like the the steam engine, for example, through pressure, another form of energy. Uh or you can transform electricity into, you know, a picture on your screen. That's, you know, what your computer does. uh transforms your raw energy electricity into you know a picture a sound or um so that's what happens all around us. It's all you know energy moving transforming energy from the sun this outer you know reactor in you know nuclear reactor in outer space beams energy at us and then what plants do is they take that energy transform you know light into biochemistry and then you get energy which used to be immaterial that gets crystallized into biochemistry and then we human beings animals eat that biochem cold energy and then the inner mitochondria that energy gets transformed Right? Again, the potential for change and then the that biochemical energy gets transformed into an electrochemical gradient. Like you charge your little batteries, your mitochondria and then that's another form of energy which again is a potential for change. And then you can make ATP with this. You can make reactive oxygen species, you can make hormones, you can you know all of the beautiful things that mitochondria do. So energy is that potential for change that has all of these different forms that continuously transforms. Amazing. Or you can use your brain to create technologies that create other forms of energy or excuse me transform other forms of energy. Exactly. uh and your question it was about you know the the human energy vitality like you know the the the energy to do something and that's I think another manifestation of energy as energy flows through this thing that we call biology or you know the the human body uh it kind of moves us into into action right and uh we know from first principles that the the the basis for human experiences you know the mind and our ability to be inspired to to feel you positive things or to feel negative things depends on the flow of energy, right? That the difference between a thinking, feeling, conscious person having experiences and uh being able to go to the gym and lift and like or and a cadaavver is really it's not the size of the muscles, the number of cells, the nucleus, the genes, the mitochondria. It's none of this. The difference between a living person and a cadaavver is the flow of energy. When you die, all of the structure, you know, the physical stuff remains as is, but energy stops flowing. If you stop breathing, if your heart stops beating, energy flow stops and then energy transformation, therefore it can't happen. And then that's what we call death and then the mind dies, right? Like you you don't have an experience anymore. And um so the flow of energy I think has to be the the the basis not only of life which we know you know to be to be correct but also the basis of human experiences and what we experience as energy. We think about energy. We we crave energy and we know and the way we talk about you know this person is really good energy or this thing you know really energize me or you know had this great idea your friend was telling you I had this great idea I'm buzzing man like what's that buzzing thing it is a real experience and uh most people have you know had the the experience of feeling really excited about something right a new idea a new person and then you know you have butterflies and you know their emotions going on in your body. I suspect emotions the best kind of first principles definition of an emotion is energy and motion and uh we can talk more about like uh what we experience in terms of energy but I think it's pretty clear we don't experience energy per se like you don't have a direct experience um an empirical uh you know access to how much fat you have in your body like there are hormones that communicate and you know how much energy is in your liver and or how much you heat uh is is in you know something what you feel what you experience is a change in energy when energy moves you feel that right and I suspect that's what emotions are there's like a movement of energy something shifts and then you experience that a bit like uh uh like if you're in a car and your eyes are closed and you're going constant speed right kinetic energy you have no way of knowing from first experience if you're going at 100 miles an hour 10 miles an hour or if you're standing still. These are very different energy, energetic quantities, right? The kinetic energy. Uh what you do feel is acceleration and deceleration. You feel the delta in energy, right? The change in energy, acceleration, deceleration. Same with temperature. Like if you touch something and it's body temperature, right? The same temperature as your hand, you don't feel it. You don't feel, you know, room temperature, you know, or body temperature. What you feel if some you touch something that's cooler than your body, what you're feeling is not the temperature of what you're touching. You're feeling your temperature leaving your body, right? It's the heat of your body leaving through conduction towards this. And then that's what you experience. And if you touch something that's hot, you're not feeling in the energy of the thing, you're feeling the heat that's coming into your body. So you feel that delta and that change. And that's how human perception also uh works. like you we're able to see colors to see light. You've studied the the visual system a lot. You know, fundamentally the ability of the eye of the retina to perceive, right? To to sense light uh requires that you bring photons, right, that are beaming from whatever source, short, long wavelength. Uh you need to bring them into stillness, right? You need to resist the flow of of of photons. And then so you change the speed of the photon and it's that change in energy. you get kinetic energy, speed of light [laughter] and then boom that when that that the the delta v the the change in in in speed uh happens this is when you can you can trigger you a calcium release and then molecular series of events and action potential and so in order to see you need to resist the flow of photons right you need to uh resist you know energy movement and then that triggers a transformation same for hearing right we here and I hear your voice uh because my eardrum resists the pressure waves that you know you're producing. So your energy is being channeled and projected through through the air as sound waves, another form of energy. And then I'm feeling you right through your energy that's carried through the air. And then because my eardrum resists the the pressure wave that you're producing and then it's that resistance right and that change that delta again in in speed by resisting your the sound waves coming from you by resisting your energy now I can perceive them and then the little osticles in the ear that transmit what used to be pressure waves into now mechanical motion and then into like fluid into the inner ear and then the cilia that move and then ions that come in then eventually they get transformed into electricity right so again it's one form of energy pressure waves turn into electricity and then the brain uses electricity as a form of energy. There can there are many right but that electricity is just so amendable to computation processing and integration. So once you have this common energetic language for sight for hearing for you know uh touch and smell and and taste then you can integrate that we perceive energy uh transformation and change in energy. We don't perceive energy, you know, per se. I'd like to take a quick break and acknowledge our sponsor, Helix Sleep. Helix Sleep makes mattresses and pillows that are customized to your unique sleep needs. Now, I've spoken many times before on the Hubberman Lab podcast and elsewhere about the fact that getting a great night's sleep is the foundation of mental health, physical health, and performance. Now, the mattress you sleep on makes a huge difference in terms of the quality of sleep that you get each night. how soft it is, how firm it is, how breathable it is, the temperature, all play into your comfort and needs to be tailored to your unique sleep needs. If you go to the Helix website, you'll take a brief two-minute quiz and it will ask you questions such as, do you tend to sleep on your back, your side, or your stomach? Maybe you don't know, but it will also ask you, do you tend to run hot or cold during the night or the early part of the night, etc. Things of that sort. 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Your description uh brings to mind a number of things but uh years ago a colleague of mine who unfortunately now has passed um stopped me in the hallway at Stanford this was Ben Barers my postto adviser later my colleague as a faculty member he said why do we have so much less energy as we get older and [laughter] I said well it's probably not a concern with you Ben I mean he was known for having tremendous amounts of energy he probably only slept four or five hours a night but in any case I said I don't know and he goes well how come no 's working on that? Like, why are we working on all this other stupid stuff? And I won't tell you what he listed off cuz some of it was stuff in his laboratory. Um, and I said, "Well, that stuff's interesting, too." He goes, "But nothing is more interesting than why we have less energy as we get older, except perhaps why it is that the brain can't change as readily and when we're young as opposed to older." you said something very important to uh underscore and that I'd like to get into a bit more which is you said you know or your partner said um uh energy is the potential for change and you mentioned emotions they stir us right and that that feeling especially of positive anticipation is so much of what we live for in fact the the signature feature of major depression is lack of of kind of any idea that there is a future worth living into apathy. So apathy etc. Whereas vitality and excitement and everything good about life is about wanting to know what comes next. So if we take a um a biohysical to cellular to psychological set of steps here we would say that somehow energy is converted into uh this internal vibration which we call emotions that let us sense physically sense into a future could be even a negative emotion but that but it still senses into a future and then you give this example very dramatic example but believe appropriate of a cadaavver where all the material is is still there right after death before it degrades right but it can't move and therefore there is no future sense it's a very a very different way of of thinking about death so let's talk about um psychological energy and physical energy that we call vitality um and if you would is a bit of a challenge but could you perhaps use that as an opportunity to teach us about these incredible organels that we call mitochondria. I use a slide uh often as an opening slide when I give presentations to academics or non-academics uh which is kind of a mitoric view of the world, right? Like at some point we realized that the the earth was not the the center of the world and then we switched over to a different form of a different you know model of the universe. So my sense is we need to do something similar for uh in biio medicine. We still have I think in most people's mind especially the older generations a very gene centric you know nucleioentric view of biology that the genes are there and then central dogma right the genes drive RNA drive protein and then drive phenotype uh and we know that that's not the full picture and there's a lot of end phenotypes for example and genetically identical mice right there are mice that all have the same genome and some are like very anxious and some are super chill it it can't be encoded in the gene somehow. We found recently that's actually there differences in mitochondria and part of the reason why these animals behaviorally are different maybe half of what half of the varants half of like the the interindividual differences what makes one mouse super chill and the other the brother the sister that is genetically identical uh very anxious has to do about with energetics in in some way. Um so I use this slide to convey this mitoric uh perspective if you want to have a copy and you know show people um I'm happy to share this and one way to understand this is energy comes into the organism as food we eat and we breathe to fuel our mitochondria right so the the reason you breathe is to bring oxygen into the body most people know this and then once oxygen is in your lungs it goes into your blood and then it goes to the heart and then the heart kind of boom distributes this you know across a whole organism. Uh and then when oxygen gets you know to your big toe or to your muscle or to your neuron and you know the your hippocampus or some brain region um what happens is the oxygen enters the cell and then once it's inside the cell it looks for mitochondria looks I mean it's attracted by a concentration gradient. So that's the mitochondria is where oxygen is consumed. uh and then when mitochondria consume oxygen they basically create a downhill slope for oxygen to kind of be attracted to that. So you breathe to bring oxygen to your mitochondria and you eat to bring electrons into your mitochondria. And uh what happens there is you know this beautiful sequence of of of a reactions where you have electrons from that were initially stuck on food by the plant. You know taking solar energy to stick electrons onto carbon and then you make hydrocarbons and then that's you know glucose or starch or and then li oils lipids everything that that's good for good fuel for mitochondria. those things, the food and the oxygen converge inside the mitochondria and then finally the uh the electrons that were you know ripped off as CO2 is broken into oxygen and and uh or reunited in your mitochondria and so your mitochondria actually make water uh and and and then release CO2. So that's the they close the life cycle that you know we have with photosynthesis. photosynthesis makes oxygen and food and then our mitochondria brings those two things together and then they release water and CO2 exactly what plants need. So it's this beautiful cycle. So when mitochondria do this uh is basically uh feeding unpatterned energy into the system and it starts with with the mitochondria the same way that if you feed electricity into a mo morse code right like t um you feed electricity it's unpatterned energy like food and biochemistry is to your body and then you by pressing and releasing a little lever right with a specific pattern what you're doing is you're patterning electricity which means means nothing. It's just, you know, raw current. And then you pattern it in something that means something. Short beeps, long beeps, and then you can spell stuff. You can communicate information, right? So you're creating information out of, you know, by patterning in in time, right? By patterning electricity. So mitochondria, the way I see them is they're kind of an energy patterning system. And we've called them the mitochondrial information processing system for that reason. Should we think of them like a little morse code um lever? I I think it's a decent you know analogy for uh you know part of their behavior, part of what they do fundamentally. They take raw energy and then they pattern that energy into molecules. This perhaps is why I've heard you say that we should not just think about mitochondria as the powerhouse of the cell generating more ATP. That is true, but it's also true that they're controlling the flow of energy in a very detailed way. Correct. And they're controlling the flow of energy, but they're also controlling um the transformation of energy, right? The electricity, you know, can be converted, transformed into all sorts of different messages, signals, right, with your MOS Morris code depending on the needs, depending on, you know, the state, depending on the person pressing, releasing the lever. Um, and sometimes the organism needs a lot of ATP. If you're a mitochondrian and you live in the heart and your job is to make ATP, a lot of ATP and then there's side jobs. If you're a mitochondrian in the liver, your job is very different and you're a very different kind of mitochondrian. Well, let me ask you this. Uh, I think you just answered the question, but are there different types of mitochondria? Yes. How does a mitochondria in the liver versus in the brain versus in the heart know to take the energy that it's transforming and pattern its output so that heart cells can do what heart cells need to do or liver or brain? Uh this seems like a very important issue. Um is it possible even that the mitochondria and these different tissues are fundamentally different organels? And we should probably define what an organel is for people. Yes. Yeah. Organel is the the technical term uh for an organ of the cell. Uh and the cell typically is represented as this you know skin and then inside the skin is the cytoplasm the big soup. And then inside the soup the cytoplasm there's a bunch of little organs that allow the cell to do all sorts of uh things and perform its activities and replicate and so on. Mitochondria is one of those organs. uh and their purpose is to uh process transform energy. Uh and one of the ways in which they they transform energy is taking raw uh energy from biochemistry the the food you eat uh empowered by oxygen to you know flow those electrons and then making building a a charge and then powering this beautiful rotor. Uh some people might have seen this. It's kind of a a rotary, you know, uh engine kind of thing. a turbine uh and then when the mito when mitochondria build their membrane potential to become charged they use that charge to power the rotation of this turbine and then as the turbine turns it converts ADP into ATP so now you have conversion of biochemistry into electricity and electrochemical charge in the mitochondria back into biochemistry ATP what's um in the backdrop of all this of course is that all of this self-organizes during development that yes the genes are the blueprint but This is all built up from scratch and probably a a a tangent for another time. But so how does a a heart cell know to produce a lot of ATP versus a liver cell? And of course it's coordinated in time with sleep and circadian stuff, but how does it know or does it even know I'm a I'm a mitochondria inside a heart cell and the amount of energy I need to transform is X? Yeah. How does a mitochondrian right singular is mitochondrian and multiple is mitochondria. Uh how does a mitochondrian and a hard cell know that it needs to be a cardiac mitochondrian right? Is that your question? Yeah. Is it is it genetically different than a mitochondrian from uh the liver? No, they're genetically exactly the same. And uh and that's another uh kind of punch to the the gene-based, you know, model of biology. How could it be that every cell in your body is genetically identical? Uh and the mitochondria have their own genetic material. You we all have our mom's mitochondria, which is really beautiful. Again, 100% of our mitochondrial genome is from mom. Is that true? Correct. Okay. And there were a few papers a few years ago that said, "Oh, no, look here. There's this like re this one case, [laughter] this one kid or this, you know, these two kids that have paternal, you know, father mitochondria." Turns out it was like a mistake in the sequencing or so mothers are truly always right. Yes. Power to power to mothers. people will be thinking and I'm also thinking does that mean and of course there are lifestyle issues but does that mean that if we were to look at the quoteunquote energy levels of mom versus energy levels of dad that what better predicts the energy levels of a kid is the mother's sort of baseline levels of energy at a given age I don't know the of studies that have asked that question about like subjective energy or like the energy to do stuff and uh which we I think we'll talk more about but uh people have looked at other more uh tractable which what we do in biio medicine we take things that we can measure objectively or like you know run on a gel or sequence or you know objectify with a biioarker in in the clinic uh people have looked at longevity right are are you more likely to live long if your mom lived long or if your dad lived long. Turns out the heritability of longevity is more maternal than paternal. uh or are you more likely to have a mental health disorder or to have Parkinson's or Alzheimer's if your mom or your dad had it? Uh some evidence say it's more maternally inherited than paternally inherited. Uh so it could be that part of uh the your ability to live a long healthy life uh or your risk or your resilience right to those disorders really are conveyed or carried by mitochondria by your ability to to transform energy. And the the reason why through evolution uh unique parental inheritance you get your mitochondria from a single parent uh has developed most people think is because there needs to be a really close metabolic energetic match between the mom and the baby right like the baby comes out and then if the mom has like a certain type of metabolism and we're all different I hope we talk about like how different we are energetically metabolically uh so we're all very different if the baby that was born was like so metabolically different than the mom, there's a chance that there would be a mismatch, right? And then the mom wouldn't be able to support through breastfeeding. Historically, that's how babies survived. Uh, and that would be a catastrophe. So, you know, it's probably a good uh system to have baby metabolism match pretty closely because they have the same mitochondria as the mom to mom metabolism. Uh, so that's I think a loose hypothesis, but it makes a lot of sense. It does make a lot of sense. Yeah, every mitochondria you have in your body, like the brain mitochondria, neuron mitochondria, astroite mitochondria, whatever your favorite cell type is, your heart mitochondria, liver mitochondria, muscle mitochondria, they're they're very different. And now we have a new method. There's a wonderful scientist in her group, Anna Monzel, who's developed a method to profile different types of mitochondria. We call this mitotyping. The same way that now in neuroscience or in immunology, it makes no sense to talk about a brain cell or like an immune cell, right? If you're a self uh you know respecting immunologists, you know, your cell types and there's, you know, at least 30 different types. Uh so I think we're at this point in mitochondrial science where we need to adopt a similar level of specificity. There are different types of mitochondria. We call those mitoypes. uh and they emerge all of them from the same mitoype in the egg right the the egg that the mother carries and you know releases from the ovary there's about half a million uh mitochondria in that egg uh and then those mitochondria there's a single type of mitochondria in there and then when it's fertilized development happens in this beautiful uh process and through that process as the heart starts to form the brain starts to form the muscles start to form the mitochondria differentiate and then you end up with different types of mitochondria that are adapted and matched to the different demands of of of cell types of organs. uh and one way we think about this is I think it's uh it makes a lot of sense to think about mitochondria as social organisms and there multiple features of mitochondrial biology that obey you know what u behavioral social scientists you know classify as as social you know if you study ants for example there's like a few rules that we know ants are social creatures because uh they form groups right and there are different types they they divide there's division of labor you have worker ants that, you know, work really hard and you have a warrior ants that are like really chubby and like they're they're here to defend the the hive. They like to fight. Yeah. Exactly. So, those two types of ants, you look at them side by side, there's like this little flimsy super like uh uh active worker ant and then this like chubby uh warrior ant. Genetically, they're they're identical. They have the same genome. They came as, you know, little larae from the, you know, the queen. Uh but their their morphology is super different. behavior is is very different. Uh but through development there are cues that you know are are um uh uh applied to the different larve and then they end up becoming a worker or a warrior. Uh so the same kind of thing happens uh in in mitochondria. So mito there are different types of mitochondria like the two types of ants. There's division of labor. There's some mitochondria for example in the muscle that are at the surface of the muscle like just underneath the saroma the the skin of the muscle cells and then there mitochondria that are inside you where the actin measin the contractile proteins happen subscar mitochondria and interophibrillary mitochondria two populations their proteom is different their their molecular composition of those different types of mitochondria are different their functions ATP synthesis reactive oxygen species production their ability to handle calcium and release calcium is different. Their morphology is very different. So even within one cell you get this uh division of labor and um uh differentiation of mitochondria and in every cell mitochondria have a life cycle. New mitochondria are born and old mitochondria die out uh which is what happens in social creatures. Um and there's a few other features like this that I think make mitochondria social organisms. And once you start to think about mitochondria as social uh creatures, then you understand maybe a little better why they need to fuse with one another. And if you if you ask Google what do mitochondria look like or chat GPT or whatever, uh the it shows you always the same kind of images. It's like a little bean. I brought one you brought one as a gift. I at one moment I thought they might be brass knuckles when you hand first handed them to me, but I said mitochondrian with the ce of the mitochondria. usually looks like this. But you're saying in in reality there'd be many of these connected to closely fused to one another. Yeah. So, and when they fuse, you get these like bean or kidney shapes or peanut shape, whatever your your preference is that fuse with one another and then they form these beautiful filaments. Uh so, if you're lucky enough to work in a lab that has one of these cool microscopes called conffocal microscope or light sheet microscopy and then you can make the mitochondria fluorescent. So you put a dye in in the dish and then it's a little fluorescent molecule that it goes inside the mitochondria. It's attracted by the big uh charge that mitochondria have uh and then you turn off the lights, look down the eyepiece and then you see this beautiful like filaments, you know, mitochondria moving. They move pretty slowly and interestingly they're just at the edge of human perception of like uh how quickly we can perceive things to move. So they move like, you know, barely fast enough so you can see them and then they they they kiss uh and and then confuse completely. Either you can invite everyone to your lab to see this, but that's a lot of people. You'd be very busy. We'll put a link to a video of this. Um we're we're building a web page called Mid Life, uh which is to help people, you know, understand themselves energetically uh and through, you know, the beauty of mitochondria. And there are all sorts of different types of mitochondria that move differently. And when the mitochondria are are not healthy and if they can't flow and transform energy properly, they start to look really weird. [snorts] It occurred to me that, you know, for the longest time, I'm 50 now, so I can say for the longest time. For the longest time, we heard that if we want energy, we need to eat, right? Of course, we need to sleep, but we need to eat. So be like and and every kid learns you're consuming energy that so that you fuel your body there all these discussions you should eat meat don't eat meat I believe you should eat some meat you should eat some vegetables some fruit etc I think you should be an omnivore some fats yes that's my my belief but we all understood that but then at some point probably about 10 years ago it became clear to people that just consuming more energy didn't give you more energy it was an obvious thing but it's now abundantly clear and based on what you're saying, it should be clear to everyone that the issue is not lack of energy going into the system. It's that the transformation of energy that occurs in mitochondria somehow is not happening correctly in people that are obese um or in people that are eating and feeling lethargic. And of course, there's blood sugar, you know, aspects to this and we could discuss all of that and we won't because that's not the topic for uh for today. But I think if nothing else, if people can just understand that they have not just these powerhouses, but these power plants within their bodies that are transforming the energy and that the mitochondria are central to how the energy is transformed and distributed on an organ byorgan basis. I think that would be a helpful concept for people to get into their mind because people are talking about mitochondria all the time. People are talking about and hearing about nutrition all the time and so often we just think about calories and you know everyone knows that you know calories is a unit of you know heat offput when you burn a given food and we learn this stuff but it doesn't transform into good health practices but I think nowadays people are starting to get a sense of of how their bodies work and you're adding a lot of important uh detail and aspects to that today. Um so I just want to frame that up. Y um if you have any reflections on that great if not it was just a point that came to mind that I think it might be useful. Yes, it's so important and we are energy fundamentally we are the flow of energy through this biological infrastructure right that we call the body but you are not the cells or the genes or right that that thing you are much more uh that energy that is flowing which is why when the energy stops flowing you are no longer when you die all the phys physical stuff remains but you you no longer have an experience you no longer exist as a as a person the way I think about this is rather than thinking in nouns, think in verbs. And I think as biologists when we teach biology, you have to teach some nouns, some names of things. But if you can get people to understand the verbs, as concepts, it's worth a a gazillion nouns. And so I think um people thinking about themselves as a verb state of as energy transformation being, it sounds so mystical, but it's not mystical. It's biochemical. it is uh I think could be useful. Along those lines, I I do want to um talk about this recent paper that you uh published uh which essentially my understanding is that looked at different brain areas and found that different brain areas have different concentrations of mitochondria. And we know that different body areas and different organs have different concentrations of mitochondria. But I heard you say someplace and this is such a beautiful sticky topic as they say that perhaps the things we do in life maybe lift weights, maybe study biology, maybe play the piano, maybe some combination of things will enrich the mitochondria, these energy transformation sites in particular organs and areas of our brain more than others. And so we really become what we pay attention to. We become enhanced for what we do. And that makes sense at the level of endurance runners run and their muscles become and everything becomes optimized for running. Weightlifterss something else. But in the brain, this gets very interesting. This means that if we read poetry for instance or study biology that the areas and circuits of the brain that are responsible for that in some sense become better at doing that. Mhm. And I think this is a very important topic because it really gets to the essence of who we are as individuals based on our choices of what to do and what not to do. So with that as the backdrop, if you could tell us about this paper and tell us about what you think about these findings and what they might mean, I I would love that. We flow as energetic processes, right? To to your point like we we are transformative processes. Like we transform, we flow. We are the energy that flows. And the more you direct energy to one area, right? If you go to the gym and you do bicep curls, like you're resisting the flow of energy while you're contracting and then you do this a few times and then when you let go, you get like blood flow, right? Energy flow through the system. Uh and we know exercise training is a beautiful example. Like if you train to run a marathon, for example, you can double the number of mitochondria in your muscles. Wow. Double, right? And my understanding of this is as energy flows through the existing mitochondria you're basically bringing you know energy into that that system and then this uh that the biochemical energy gets transformed and into molecules into metabolites and then eventually into proteins and then structure gets created as energy flows right so it's the flow of energy first you resist it that's we call this energy resistance and and then when you let go of of the resistance it's that's when we build. That's when we grow. That's when, right, Arnold Schwazer said, um, muscles are torn in the gym. They're fed in the kitchen and are, um, grown in bed, I think, is, um, in an Austrian accent. Yes. So, um, so yeah, if you direct energy towards a muscle, right, then one way to direct energy is to resist the energy flow and then to to let go. And that's what exercise fundamentally is, right? You resist the energy flow and then you let go. When you resist energy too much, it feels uncomfortable which is like the the burning pain of of and then when you let go is when growth and uh you know building can happen. Uh and we know the same thing happens like everywhere. This is this is not like a mysterious thing of the muscle and like of exercise uh you know physiology. This is a fundamental biological principle. If you flow energy in one area then it will grow. It will you know get better. it will get more efficient. And if you block energy flow to one area like you block blood flow for example or you get an accident and the nerve gets you know damaged then the the muscle doesn't contract anymore you're basically blocking the flow of energy there and what happens it atrophies right atrophy is a normal uh movement of life when energy flow decreases and if if there's no energy flow really there's no purpose for that structure if you feed if you stimulate that structure be it a muscle or brain circuit, right? A brain network or brain area. Uh then naturally, you know, that that area should uh should grow and and and build. Uh and there what we know happens in the brain and also happens between different organs of the body is there's kind of a competition for finite energy resources. Right? What you said earlier like you can't just eat more to get more energy. We know now we know very well if you overeat, right? you eat more than your body is actually flowing consuming in terms of energy transforming you get sick like if you can you put on fat which is a good adaptive uh coping mechanism to eating too much uh but then eventually the systems like it gets overwhelmed and then that hurts the mitochondria and it hurts you know cells to become insulin resistant and so there's all sorts of consequences to eating too much you cannot eat more to get more energy and that is I think still scientifically a very big mystery, right? That why can't we just ramp up our energy uh consumption, energy transformation and then like sleep less and you know uh work out 3 hours every day that even like professional athletes who devote all of their energy to you know building muscle mass, building skills or you know building aptitudes, there's a limit to how much you you know you can eat. Uh and they're they're yeah we don't really know why that is why there's a limit to that. And uh so the body operates an economy of energy. You have x amount of energy. You can push that up, you know, over short periods of time. Like if you start to work out and you're you're a cyclist, you do the to France, right? Like three weeks, you're you're going for like five 7,000 calories a day. You do this for three weeks. There's a reason why the to France is not four weeks and five weeks, right? There there's there's a cap. And there's beautiful data showing that the longer the event the athletic event the lower the max output per day and and if you looked at that curve you know the the first point max power output you can develop over 10 seconds is what you see in the 100 meter sprint right and then you get the uh 400 meters and and then it goes down at the very and the to France is you know marathon is here to France three weeks is here then you get like crazy run across America multiple weeks and then at the very end nine months pregnancy and [snorts] it costs energy to grow a human being and uh some of the data suggest that when you grow a human being for 9 months you're basically operating at the max of her capacity if you integrate over you know a 9-month period. Do pregnant women accumulate more mitochondria or the energy demands are entirely for the mitochondria of the developing fetus? That is a good question. We know certain brain areas grow during pregnancy that the brain remodels. Exactly. Uh there are different demands, right? As a mother, if you're pregnant now, you need to start to care about different things. Maybe it's adaptive to start to think about the world slightly different way. And it's not just just about yourself. And um so there there are certainly and even long-lasting brain changes happen in in the woman's brain. So this economy of energy between organs is likely what explains if you're a young woman and you exercise a lot, you lose your menes, right? Aminora, then this is not because the the reproductive system is broken or because the ovaries are or are sick or something like that. The best explanation we have is there's a short shortage of energy. Like you're pushing and driving all of your energy budget towards your working muscles towards making more mitochondria in your muscles and there's no more energy to fuel to to to fuel uh reproduction. I have a practical question related to this. I have always wondered why is it that when we're coming down with a cold or a flu or some sort of other infection that there are a bunch of processes that make us uh more lethargic and tired and these are very adaptive and we know we need to rest. But it's not just about getting sleep. We actually need to slow our circulation down. We need to rest. And there all these theories, you know, about do you feed or starve a cold or flu. And I covered that in a different episode. We'll put a link. It's not straightforward, but um follow your appetite, stay hydrated, keep your electrolytes up and so forth is the short answer. But is it that the immune system needs more energy and the body as a protective mechanism, as an adaptive mechanism is saying slow down everything else and devote yourself to uh healing, to fighting this infection as opposed to spending energy even walking up the stairs as much as you typically do during a day. Is that the is that the idea? Yep. I think that's the best model we have. Uh and I had a personal experience of this uh over a New Year's a couple years ago where I I could feel I was, you know, coming down with something uh before the, you know, New Year's dinner. And so it ended up being a pretty short night. I went to bed early and that night was terrible. The next day I was so uh so off and I was, you know, starting to work on on the book Energy and then I thought, "Oo, this is such a a cool opportunity." Like now I'm experiencing I'm feeling drained, right? Like I'm in bed, everything hurts. And then I thought I should be writing about this, right? Like and then I I thought like just the the thought of like grabbing my computer then I shouldn't cost more doesn't cost a lot of energy just like wiggle my fingers on the keyboard. But you know there was no drive. I stopped caring about stuff that I usually care about, right? Everyone has experienced this when you're really sick. Uh motivation, right? zero. Um, my capacity to be the best human being that that that I am and to be kind a little diminished. Just like [snorts] I was just trying to survive, you know, like and and what we know in terms of biology and mitochondria and energy that happens when you're fighting something like this, the immune system cost a lot of energy. Mhm. Uh so I think the best model interpretation we have of sickness behavior is what you were describing the technical term is you feel sick right and you don't want to move the body you feel cold right which then uh forces you to put covers or you know to to dress to avoid cold environments uh you it it hurts to move your body like to contract muscles and like the the there's alodmia right the sensitiz you become more sensitive to pain all of these things uh likely exist in service of conserving your precious energy budget and even not eating right like follow your appetite. Yes. And and if you you know eating costs energy nothing in biology is free. Everything costs something. And if you eat food now you need to masticate. You need to like have peristelsis. You need to have gastric acidification movement you know secretreting digestive enzymes and maybe some bile. Like there the the orchestration of digestion is pretty expensive. It's like 10 15% of your daily energy budget. So that's a 10 15% of your daily energy budget if you're running like a limit is a lot. By now I'm sure that many of you have heard me say that I've been taking AG1 for more than a decade. And indeed that's true. The reason I started taking AG1 way back in 2012 and the reason why I still continue to take it every single day is because AG1 is to my knowledge the highest quality and most comprehensive of the foundational nutritional supplements on the market. What that means is that it contains not just vitamins and minerals, but also probiotics, prebiotics, and adaptogens to cover any gaps that you might have in your diet while also providing support for a demanding life. Given the probiotics and prebiotics in AG1, it also helps support a healthy gut microbiome. The gut microbiome consists of trillions of little microorganisms that line your digestive tract and impact things such as your immune status, your metabolic health, your hormone health, and much more. Taking AG1 consistently helps my digestion, keeps my immune system strong, and it ensures that my mood and mental focus are always at their best. AG1 is now available in three new flavors: berry, citrus, and tropical. And while I've always loved the AG1 original flavor, especially with a bit of lemon juice added, I'm really enjoying the new berry flavor in particular. It tastes great. But then again, I do love all the flavors. If you'd like to try AG1 and try these new flavors, you can go to drinkag1.com/huberman to claim a special offer. Just go to drinka1.com/huberman to get started. You mentioned that if women exercise beyond a certain threshold, uh they stop menrating and that it's because there's not enough energy essentially to menrate. One idea would be well if you just eat enough then you have enough energy. But we have to think in verb states not absolutes. And so what I'm realizing is that while one needs sufficient energy input in the form of food and this could also be true for the example of being sick, it's necessary but not sufficient because the mitochondria are doing two things. They're transforming that food energy into bodily energy to menrate or to move or exercise or think or care about a book etc. But part of their job is not just to transform the energy, it's to distribute the energy. And so you really need two conditions and you know I'm not a computer scientist but I know enough about programming you know and engineering that you know this concept of an andgate you need sufficient energy so coming into the system and you need to be able to distribute that energy properly in order for something to occur it's an endgate you need both things basically so I now and forever going forward will think about mitochondria as not just energy production but energy distribution organal Yes, thanks to the way you described it. And now it makes perfect sense as to why when I'm sick, if I'm not hungry, I'm not going to force myself to eat, provided I have enough body fat stores, you know, I need to eat eventually, but whatever weakness or fatigue I feel is probably in that situation where I don't have an appetite is probably not a lack of caloric energy driving that fatigue. It's that my body is saying, you know what, you're better off just not having me shuttle that food energy through you so I can shuttle your immune cells to the proper place. Exactly. And this is when people say the body is smart. There's an intelligence to the system. I think that's true because with our brains, we think, oh no, I'll just cram more energy into you need to eat. You need to No, maybe not. Whereas if I do have an appetite, I don't care what people say about feed a cold, starve a flu or feed, you know, starve a flu, feed a cold. I'm just going to do what my body tells me to. Yes. Yes. And I I agree the body is wise. Animals who don't have a very other non-human animals like your dogs uh like they they don't have a mind to distract them from, you know, living in alignment with their energetic states. So when they're sick, the immune system just the the amount of the the part of your budget that gets consumed by the immune system, you know, expands, right? So this energy this extra energy needs to be stolen from somewhere because you can't eat more to have you know infinite energy. Uh so what where's that energy coming from? So not contracting your muscles because you feel in pain is a good way. Not having to thermmorreulate because you you know cover up another way to conserve energy. and then stopping to care about stuff like becoming asocial and apathic and all of those features of sickness behavior or energyconserving uh strategies and not eating like if you can have like free 10 15% of your energy now you can allocate it to your immune system that is a very good strategy most people walk around with multiple weeks if not months worth of energy right like under the skin and their love handles uh the record actually for not eating is from this uh Scottish man. 382 days. Was he fat when he started? He was very fat. Was he fat when it ended? Uh he lost uh how much he lost like 250 lbs I think. That's all stored sandwiches. Yeah. So most people can eat can go a full month without eating. So So and this maybe goes back to what we talked about earlier like we don't feel energy quantity, right? Like uh if you close your eyes and you feel your energy like you don't feel how much fat you have on your body, how much glycogen you have in your liver or you know in your muscles. What you feel is the transformation of the neural energy. Do you want to do a little experiment? We can do a little experiment to to feel our energy. Definitely. Yeah. Okay. By the way, a a a tenure full professor at Columbia School of Medicine just said, "Uh, do you want to do a little experiment to feel your energy?" and we both closed our eyes, which tells you that it's definitely 2025. [laughter] You know, the reason good things have happened in the world. The reason we both closed our eyes and kind of stopped moving our our bodies, which is kind of what you do if you want to meditate or something like this, is because it turns off the noise. Right. And the if you want to survive in a dangerous physical world, you need to be aware of like stuff that might hurt you, right? Or kill you. Um and feeling your body like propriception and all of this needs to be very high level. Yeah. It needs to be prioritized over whatever intraceptive you know signal there are. There's some intraceptive signal that's what we'll feel into that you know can overcome that but just not moving the body closing your eyes it kind of helps you to tune into your energy and I suspect there's a lot of value there. Yeah. We'll talk more about some incredible results about meditation and and restoration of energy. Um, can the audience do this along with us provided they're not driving? Yes. Yes. Okay, great. Yeah. Uh, so to do this, uh, best is you're sitting comfortably and, um, you can close your eyes if you want to. I think that helps with the the process. We'll take one breath in and then, uh, we'll we'll hold the breath for a little bit. So, breathing in, [snorts] breathing out, and you can breathe out all the way, all the way down. And then hold that breath. And for the first few seconds, it's generally not too uncomfortable. But then as you hold this, feel into your body, to your belly, into your chest, into your head. What's the effect of not breathing? And then you start to feel maybe this urge to breathe and this desire to bring oxygen into your body, to your And then when you need to, you take a breath in. You can open your eyes. If you can hold it longer, you you do. Yeah. What did you feel? So when I went to the full exhale and held my breath, uh my what we geek speak, what neuroscientists call interosception, my perception of things from the skin inward became more salient and I could feel my heartbeat uh more and more. Um, and then it didn't speed up, but I could just feel my heart beating. I was more aware, excuse me, of my heart beating. And then I, as the impulse to breathe started to kick in, uh, you could feel a bit of ramping up of it's not anxiety, but it's a sense of urgency, you know, hardwired, fortunately, sense of urgency. And then with an with an inhale, there's a a relaxation of of that sense. Y and um there is this sense that uh energy moves out from the center at that point like like you feel more of your body because I think anytime we don't have air um our brain goes to how do I bring air right here right now you're not thinking heartbeat you're thinking get get air something of that sort yes I think if you do that and the the the urgency right the anxiety the stress or um this you know it feels dangerous right and And I think to many people dying by drowning or like suffocation is like the the the one of the worst death. And uh so why is that? Like what is that sense of urgency of anxiety? It's CO2 building up in your blood. Right? CO2 is the product that mitochondria release as they transform energy. And then when CO2 builds up, it means oxygen is getting depleted. Right? If oxygen gets depleted, the electrons from the food you eat can no longer flow. Right? If there's no oxygen at the end in your mitochondria to accept the electrons flowing, you stop flowing. So you as a movement of energy are at risk of of ceasing to exist. Not being able to breathe, right? Uh being out of breath is an existential threat to your energetic self. Without getting into the details, I've talked about it on other podcasts. I had a a scuba diving accident a few years ago, 2017. ran ran out of air in a in a bad situation to begin with. Um and I'll tell you the sense of urgency is very immediate and um fortunately didn't end up with any PTSD from that. It obviously worked out okay. I'm I'm sitting here and talking. But um now I understand why. And I never did this to another kid, nor did anyone ever do it to me, but there's this joke that kids play on one another where their friend is coming up from underwater and you're ready to take a breath. That's why you come up from underwater. And if someone holds your head right at that point, even though it's just a m a moment, the sense of urgency that kicks in is very intense and very very fast. Uh which speaks to just how hardwired these circuits are because at that point presumably there was enough air to stay under for another 5 seconds or whatever it is. But when we anticipate getting oxygen and we don't, there's a big increase in stress. energy goes straight to whatever whatever areas of the brain, amydala and other areas presumably that are like this is a bad situation do anything and everything becomes about resolving this situation. Yes. And and that's because we are energy. We are the flowing energy through the system. And if energy uh starts to stall, it just feels so uncomfortable. We have to have evolved to to feel this. If something is making your energy stall, like there's not enough oxygen around, you need to get out of there. And you need to have this instinct, right, to to survive. So, what's trying to survive is not like the the physical body. It's it's the this flow of energy that's, you know, being threatened, right, from from lacking oxygen. Many times already, you've talked about the flow of energy, and that concept, I think it's going to be threaded through as we go forward. when you hear about um practices like Tai Chi or when you hear like in the martial arts where people are taking other people's energy and you know converting and this is a not just a thing of like of iikido but the notion that like if you box you learn that you you're not just hitting with your arm and your shoulder you have to keep your feet planted you're pulling from the floor in some sense you're transferring the energy but you're actually pushing back against the floor and then it's coming up through your body people talk about the fascial slings you know when people run there There are a bazillion different variations on this, but it's all about this concept of flow of energy. And I find that so much of what we find incredible when people dance, when people uh sing, when people uh do incredible athletic feats or channel everything they've got into something. This channeling of energy is the human animal deliberately channeling all their energy in the form of practice into something. In many ways, we love that. Even though by definition it creates a very uh lopsided person and I I'm not trying to get into the psychology of this so much as I want to go back to this notion of our brain areas having different amounts of mitochondria probably from birth but then if we play soccer and we like math and uh pottery we get a different brain than if we like reading and theater and movies and We'll exercise, but we're not too crazy about it. You know, if we exercise, our brain works better. We've heard, but there's also the notion of the person who just spends all their time exercising and their brain doesn't get better. I'm being gentle there. And I like exercise and I like thinking. So, is there a trade-off? Is there a trade-off? Because I believe in staying fit and staying healthy and living a long life, but most people are not competitive athletes. Most people don't want to be the strongest person in the gym or the best runner. Most people, I believe, and I'm one of these, I want to be strong enough. I want to have endurance. I want to have some speed, but I want to be able to think. I want my mitochondria balanced across all my systems. My girlfriend would say, "Well, you're a Libra. Of course you do." But I'm saying I want it because I want to be able to lean into a lot of different aspects of life. I don't want to become the atrophied in one area and hypertrophied to some great extent in some other area, human. Yep. So, what are your thoughts on these through the lens of the results that you recently published? Is it a trade-off? I don't think we know uh exactly, but we did a study recently that points to the fact that there might be trade-offs between different systems. Sorry, meattheads. No, I'm just kidding. I love I love working out in the gym, but you have to read too, you know. You know, we we tested the hypothesis that if you have more mitochondria in your muscles, you also have more in your brain and then your heart and then your liver and then your skin. And the result is that's not the case. And you know, you Andrew, I think you seem to derive a lot of fulfillment. And um you know, you live up to your full potential when you can do all of these things, right? And you're a great communicator. You're a great integrator. You know, the kind of thinking you do is like this this beautiful integrative thinking uh which is which might be what has led you to do what you do now, right, for with most of your time because this really taps into your strengths. It really moves you, I suspect, energetically. I think I enjoy it. You enjoy it. What does that mean? Right? Enjoyment is kind of an emotional state, an affective state that it's an energetic state. We're all different energy transformers, right? Like you transform energy and you have this ability to do what you do. Other people have very different skills, right, and gifts. I think we we're born with something that uh doesn't seem to be fully just encoded in in people's genomes. [laughter] there are genetically identical twins that have very different aptitudes and you know personalities and we don't know where this comes from. Um and and then we are fed we're you know moved and inspired by different things and uh when people seem to follow that it it appears to bring them energy and what this means biologically the level of mitochondria I think our our research is starting to to point in a direction that says if you're engaged in things that bring you purpose and fulfillment there's another study we did we asked people our colleagues in Chicago ask people before they died. How do you how much uh sense of purpose do you have in your life? How meaningful social connections, well-being, right? Uh and then the negative stuff, depression, loneliness, you know, anxiety, uh and then every year they answered those questionnaires. So, we knew how deep people felt about themselves, about life, about, you know, some greater power, you know, beyond them. Uh and then they died, gave their brain to science. We got a little piece of brain and now we're measuring the mitochondria. uh and Cavalyn Trump uh a researcher who works in her group who's a a bonafide mitochondrial psychobiologist. So she asked questions between the psyche and and the and the biology of mitochondria. So she asked could it be that how people felt before they died relates to the bitochondria in their brain and the prefrontal cortex the DLPFC the dorsalateral prefrontal cortex. And what she found is that people who felt more purpose in life and who felt more connected to others and who felt you know well-being uh for whatever whatever was bringing them well-being it seemed like that was sufficient to increase the energy transformation capacity of the mitochondria in their brain. So is this because of the experiences that you know they're fortunate to have or that they're actively fostering in their life uh that's actually transforming the mitochondria in their brain maybe. Or it's the other way around for some reason that we don't understand they have more of the energy transformation capacity in their brain mitochondria and that is leading them to experience the world as more positive and as more purposeful and as more meaningful. Right? Animal studies say it probably goes both ways. So if you tweak the mitochondria in a rat brain, you can change the behavior of that animal to from more submissive to more dominant or from more dominant to more submissive. Beautiful work by Carmen Sandy at EPFL in Switzerland that showed this. Uh and then the other way around, if you chronically stress animals, you deprive them of kind of freedom of choosing different, you know, options. So chronically stressful things actually damage the mitochondria in the brain. And there in some brain areas there are fewer mitochondria and they don't transform energy as well. So the mitochondria are responsive it seems to our states of mind. Uh and that the mitochondria in our brain can also influence our states of mind. And and if if we want to talk about the philosophy of this thinking about like what's causing what maybe is and you're really the right question to ask but what's emerging is that's relevant to your question. There's a clear connection between the subjective experiences that we have that we know from first person to be meaningful, right? Because that's what we have access to uh primarily is how we feel, how we experience the world somehow is related to the biology of the energy transforming units, energy processing units in our brain, man. Uh and and maybe also in our immune system. And so we've done work in immune cells and in brain tissue. Um, and we're currently analyzing mitochondria from 5,000 uh human brain samples. That's 10 different uh brain and and muscle uh samples from 500 people. Do you have histories on these people as to how much purpose, what they did, how life how much life fulfillment they had. I'm so glad that biologists like you exist. I just want to say that uh not just because you're agreeing to be a public health educator, but um just it's incredible how much things have changed in the last few years in terms of the public awareness about biology and psychology. But I I have the genuine sense that with you doing the kind of work that you're doing that no longer are we going to be talking about the eastern philosophy of energy versus you know mitochondria in a laboratory at some medical school at an Ivy League medical school. But you're merging these ideas in in real data. And I think it's going to bring together ideas that have been in cooperation for a long time but didn't realize it. And I think it's going to transform human health because if we think about ourselves as energy transformation beings, we're going to think pretty carefully about where we invest our time and energy and also I do think start to listen to our bodies more when we're feeling shut down. Like what does that mean? You know, uh now we can't respond to everything as just a well does it give me energy not give me energy because we also have to build up some circuits to be proficient in life that perhaps are inconvenient for us to build up. But at the same time, I think there's a lot to be gained from this idea of does something give me energy. Does this I think people uh confuse like drama and friction with certain people. It's like that's energy expenditure. That's not that's not good transformation of energy. And you hear about this stuff now more in the psychology relationship space. People will say, you know, they're not good for my nervous system. It's so funny how neuroscientists now, you know, where or I just feel relaxed around them or I can sleep next to them so comfortably. And you know, we kind of write these things off as like, oh, that's cute. That's kind of woo. Uh-uh. This sounds like real biology if pushed through the lens of what you're telling us about mitochondria as energy transformation units. Yep. I think everything you just mentioned doesn't make much sense from this molecular biology lens that's really captured biio medicine, right? like many years ago, 50 years ago or so, like there was this wave of whoa, there there's DNA that exists and there's, you know, proteins, we can sequence stuff. We can measure, you know, uh the components of a cell and we can look at things under the microscope and we can, you know, scan the brain and like all of those um um assets that we were, you know, all of a sudden able to to capture. It was really convincing, compelling. We built a whole research and you know academic science ecosystem around this and I think as a um by by nature this reductionistic framework pushed aside the mind right the the all of the subjective experiences you know it's in your head or you know whatever all of this was pushed aside so the human experience is the most direct way in which you can know whether the content of your life matches your your energy right and matches what matters for you and uh and what you really care about. Uh so like pushing aside which is what biio medicine has done pushing aside the mind and all of those subjective experience I think has been really um damaging to understanding the basis of health and understanding what allows some people to be healthy for like really long time and to live long healthy lives and to live you know fulfilled lives. um we we if we if we think of ourselves as molecular machines like there's no way we can make sense of this and then we have consciousness you know research that's trying to make sense of of these beautiful uh this beautiful spectrum of human experience right from like I can't get up in the morning like taking a shower is like too difficult and I'd rather die like this is one end of the spectrum and then the other end is oh my god the world is so beautiful I'm so grateful I feel inspired to be a good person um and I can do good in this world, right? There's and then everything in between and we're left now we don't have a science of this like we've we've said this is not science, right? This is like psychology. This is woo stuff and and we can't access this with biomolecular science. And I think it's true. I I I'm not uh I don't have a lot of hope that we will make great inroads in fully capturing the nature of consciousness, the nature of the human experience, the nature of well-being, of what it means to be a fulfilled human being that lives up to their full potential. I don't think at the at this point that we'll find answers in molecular biology. But what I do think is that an energetic understanding of life and an energetic understanding of ourselves, right? As an as a flow of energy, not as a molecules and the metabolism that support this flow, but as the flow itself. I think that is kind of a point of consilience. Energy flow is the lynch pin between matter, you know, the stuff of biology [laughter] and experiences. Again, we don't experience energy itself. If we experience a transformation of energy when energy flows through this metabolic circuitry that we have, metabolism is just an energetic circuitry. Electrons flowing not as free electrons in a a copper wire but as electrons from food to oxygen through enzymes. Right? So this thing is a a metabolic carbon-based you know energetic circuit. And when energy flows through this somehow for reasons we don't fully understand it feels like something right and emotions energy in motion subjective experiences of feeling inspired and and doing good or feeling terrible wanting to die like these states all live and all emerge from the transformation of energy. Energy is kind of that consilience point where we have you know behaviors uh everything we do in neuro imaging right the EEG whatever when we look at the brain we're really looking at energy patterns if you just change how much energy flows in one region or another you change the anatomy you change the biochemistry and then that gets encoded if energy flows a certain way or is patterned a certain way it will change how genes are expressed right it will change the epiggenome because of metabolites and whatever intermediates are are there acknowledge one of our sponsors, Function. Last year, I became a Function member after searching for the most comprehensive approach to lab testing. Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health. This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more. 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There's so many things related to your mental and physical health that can only be detected in a blood test. The problem is blood testing has always been very expensive and complicated. In contrast, I've been super impressed by Function's simplicity and at the level of cost. It is very affordable. As a consequence, I decided to join their scientific advisory board, and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, you can go to functionhealth.com/huberman. Function currently has a wait list of over 250,000 people, but they're offering early access to Hubberman podcast listeners. Again, that's functionhealth.com/huberman to get early access to Function. What I think has been missing in this whole landscape of health frankly has been somebody who understands the different levels of analysis. Uh a great neuroscientist at uh now at NYU once told me that a a real intellectual of which you are is somebody that understands and can communicate something at multiple levels of granularity. That's very very important. So I'm very reassured by everything I'm hearing and where this is taking us. That takes us to your opening question which is like takes us through mitochondria and how that you know affects cellular and organ and you know behaviors. I think what we just touched on here is like mitochondria flowing transforming energy and then that energy kind of ripples out at the level of the cell and their metabolites that are mitochondria are producing based on the energetic state of the mitochondria. there will be more you know acetyl coa and citrate and uh lactate and alpha ketoglutarate and those are all you know molecular uh imprints of an energetic state and then those molecules carry this energetic signature that's in the mitochondria to the nucleus and then boom they get written down as the epiggenome and now the cell all of a sudden has this gene turned down turned off or this other gene turned on and now the cell is a different kind of cell because there was a change at the energetic level in the mitochondri And then that ripples out. Now the cell, you know, experiences its environment in a certain way energetically, right? That starts in the mitochondria, ripples out to the nucleus. Now the nucleus is able to make proteins like cytoines. And so cytoines in many ways are uh signatures of an underlying energetic state. So what we call inflammation, my understanding of of inflammation is it's an energetic state. And in many cases is if the energy doesn't flow freely or you know with low resistance in the system if you're a cell and either you're running out of oxygen right you're hypoxic electrons can't flow as a cell you know you have this primal experience of what you experienced earlier right you're not breathing you're like I I have to take a breath or I'm going to die so if you're a cell and you experience a version of this a really primal version of this you need to do something so you call out you call out you call out for help and that's where the cytoines come in. Yeah, cytoines are, you know, universal language of cell cell communication. Cytoines are not immune. They're they're there this you know fundamental way that cells have to talk to each other. Assuming that it is this repeating set of principles of of energetic flow. Let's get a little woo for a moment. Let's get really woo for a moment. We are in California. Uh because I am beginning to understand it's grounded in real biology. For instance, people have heard of the 27 club. You know, you have there's this uh uh it's not a club anyone wants to be a part of, which are, you know, incredible musicians and artists who just seem to have this incredible uh talent and intensity and they die at 27. And um you know and there of course certain things like music and art sometimes are you know there's overuse of substances and substances were almost always involved in these various cases. Jim Jim Morrison and Jimmyi Hendris and you know Janice Joplain and there are others. I don't know if they're all in…

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