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

What's the deal? Can people reverse the grain of their hair by reducing their stress? Can people accelerate the grain of their hair by stressing more? Likely both are true. Yes. Okay. And I think what we discovered is that hair grain at least temporarily is reversible. This was surprising because it goes against this notion that aging is a linear you know process that just happens over time no matter what you do and here we should know actually a hallmark of aging which is you know deep pigmentation losing color in your beard and your hair It's something that happens to almost everyone but at different you know stages of life 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 as 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 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 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 longevity is genetically Inherited maybe and then about 90% is not welcome to the Huberman lab podcast We discuss science and science-based tools for everyday life I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine My guest today is dr. Martin Picard. Dr. Martin Picard 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 organelles 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. Picard explains Mitochondria 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 organelles work to produce energy And as the 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 Picard dr. Martin Picard 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 gonna 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 organelles 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 That graying of hair is not a prerequisite 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 Mm-hmm 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 Feynman who is like this amazing science communicator physicist So that 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 and light energy electromagnetic Kinetic energy movement speed right potential energy so Energy kind of manifests in all of these different ways So in in a nutshell, I think the best definition I've heard from my wife in Russia is who's a biophysicist 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 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 Celsius right the human body It gives us the potential to move and muscles to contract and you know our biology to do 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 So the potential for change and then it manifests in all these beautiful ways And it's something that flows, you know when a key property 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 steam engine for example through pressure another form of energy or you can try to transform Electricity into you know a picture on your screen. That's you know what your computer does transforms your raw energy electricity into you know a picture a sound or 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 and you know nuclear reactor in outer space beings energy at us And then what plans 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 biochemical energy and then the in our mitochondria That energy gets transformed right again the potential for change and then the biochemical energy gets transformed into an Electrochemical gradient 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 can 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 and your question. It was about you know the the human energy vitality like you know 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 human body It kind of moves us into into action, right? And 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 know positive things or to feel negative things Depends on the flow of energy right the difference between a thinking feeling conscious person having experiences and Being able to go to the gym and lift and like and a cadaver 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 cadaver is the flow 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 So the flow energy I think it 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 had this great idea. I'm buzzing man. Like what's that buzzing thing? it is a real experience and most people will 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 There are emotions going on in your body I suspect emotions the best kind of first principles definition of an emotion is energy and motion and We can talk more about like 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 an empirical 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 know heat? Is is and 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 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 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, that'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 works like you Were able to see colors to see light you've studied the visual system a lot You know fundamentally the ability of the eye of the retina to perceive right to sense light Requires that you bring photons right that are beaming from whatever source short long wavelength You need to bring them into stillness right you need to resist the flow of of photons And then so you change the speed of the photon and it's that change in energy get kinetic energy speed of light and then boom that when that the the delta V the change in and speed Happens this is when you can you can trigger your 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 Resist you know energy movement and then that triggers the transformation same for hearing right we hear and I hear your voice Because my eardrum resist 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 All right through your energy That's carried through the air and then because my eardrum resist the the pressure waves that you're producing and then it's that Resistance right and that change that delta again and speed by resisting your the sound waves coming from you by resisting your energy Now I can perceive them and then there are little obstacles 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 to move and then Ions that come in then the eventually they get transformed to electricity, right? So again, it's one form of energy pressure waves turn it to electricity And then the brain uses electricity as a form of energy that can there are many right? But that electricity is just so amenable to Computation processing and integration. So once you have this common energetic language For sight for hearing for you know touch and smell and taste then you can integrate that We perceive energy Transformation and change in energy. 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This was Ben Barris my postdoc advisor later. My colleague as a faculty member. He said Why do we have so much less energy as we get older? And 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 one'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 because some of it was stuff in his laboratory And I said well that stuff's interesting to he goes but nothing is more interesting Then 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 underscore and that I'd like to get into a bit more which is you said, you know Your partner said Energy is the potential for change and you mentioned emotions They stir us right and that that feeling especially a positive anticipation is so much of what we live for in fact that the signature feature of major depression is lack of of Kind of any idea that there is a future worth living into So the apathy etc. Whereas vitality and excitement and everything good about life is about Wanting to know what comes next so if we take a biophysical to cellular to Psychological set of steps here we would say that somehow energy is converted into this internal vibration which we call emotions that let us sense Physically sense into a future Could be even a negative emotion, but but it still senses into a future and then you give this example very dramatic example, but I believe appropriate of a cadaver Where all the material is still there right after death before it degrades right but It can't move and therefore there is no future. I can't sense a very very different way of thinking about death so Let's talk about Psychological energy and physical energy that we call vitality And if you would it's just a bit of a challenge But could you perhaps use that as an opportunity to teach us about these incredible organelles that we call mitochondria I use a slide often as an opening slide when I give presentations to academics or non academics Which is kind of a mitocentric view of the world Right like At some point we realized that the earth was not the the center of the world And then we switched over to a different form of a different model of the universe So my sense is we need to do something similar for in biomedicine We still have I think in most people's mind, especially the older generations a very gene-centric You know nucleus centric view of biology that the genes are there and then central dogma, right? The genes drive RNA drive protein and then drive phenotype And we know that that's not the full picture and there's a lot of and phenotypes For example and genetically identical mice, right? They're mice that all have the same genome and some are like Very anxious and some are super chill. It can't be encoded in the gene somehow We found recently that's actually their differences in mitochondria and part of the reason why these animals behaviorally are different Maybe half of what the half of the variants half of like the inter individual differences What makes one mouse super chill and the other the brother the sister that is genetically identical Very anxious has to do about with energetics in some way So I use this slide to convey this mitocentric Perspective if you want to have a copy and you know show people 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 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 the distributes this, you know cross a whole organism And then when oxygen gets you know to your big toe or to your muscle or to your neuron and you know That your hippocampus or some brain region What happens is the oxygen enters a 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 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 What happens there is you know this beautiful sequence of Reactions where you have electrons from there were initially stuck on food by the plants You know taking solar energy to stick electrons onto carbon and then you make hydrocarbons and then that's you know Glucose or starchy and then lip oils lipids everything that that's good for good fuel for mitochondria those things of food and the oxygen converge inside mitochondria and then finally the The electrons that were you know ripped off as co2 is broken into oxygen and Are reunited and you mitochondria and so you might have congee actually make water 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 is basically feeding Unpatterned energy into the system and it starts with with the mitochondria the same way that if you feed electricity Into a more morse code right like 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 the specific pattern what you're doing is your patterning Electricity which means nothing. It's just you know rock 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 there 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 Lever I think it's a decent you know analogy for You know part of their behavior part of what they do fundamentally they take raw energy and then they patterned 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 Morse code Depending on the needs depending on the you know the state depending on the person pressing releasing the lever 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 mitochondria and in the liver Your job is very different and you're a very different kind of mitochondria. Hmm. Let me ask you this 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 This seems like a very important issue. Um Is it possible even that the mitochondria and these different tissues are fundamentally different Organelles and we should probably define what an organelles for yes, yeah organelle is the the technical term for an organ of the cell 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 is a bunch of little organs that allow the cell to do all sorts of Things and perform its activities and replicate and so on mitochondria is one of those organs uh, and their purpose is to process transform energy and one of the ways in which the transform energy is taking raw energy from biochemistry the food you eat Empowered by oxygen to you know flow those electrons and then making building a charge and then powering this beautiful rotor some people might have seen this it's it's kind of a a rotary, you know Engine kind of thing a turbine And then when the 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 a dp 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 the Yes, the genes of the blueprint, but this is all built up from scratch. I'm probably a Tangent for another time, but so how does 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 heart? I'm a mitochondria inside a heart cell and the amount of energy i need to transform is x Yeah, how does a mitochondrion or singular is mitochondrion and multiples mitochondria How does a mitochondrion and a heart cell know that it needs to be a cardiac mitochondrion? Right is that your question? Yes. Is it genetically different than a mitochondrion from Uh, the liver no, they're genetically exactly the same and uh, and that's another Kind of a 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 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 a read this one case 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 quote-unquote 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 Which we can I think we'll talk more about but People have looked at other more tractable which what we do in biomedicine we take things that we can measure objectively or like, you know run on the gel or sequence or You know objectify with a biomarker in the clinic People have looked at longevity right or are you are you more likely to live long if your mom live long or if your dad live long? turns out The heritability of longevity is more maternal than paternal Or 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 Some evidence say it's more maternally inherited than paternally inherited So it could be that part of the Your ability to live a long healthy life 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 You need parental inheritance you get your mitochondria from a single parent 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 and energetically metabolically Uh, we're 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'd be a mismatch right and then the mom wouldn't be able to support through breastfeeding Historically, that's how babies survived And that would be a catastrophe. So, you know, it's probably a good System to have baby metabolism match pretty closely Because they have the same mitochondria as the mom to mom metabolism So that's I think a loose hypothesis, but yeah, that 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 astrocyte 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 our 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 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 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 mitotypes And they emerge all of them from the same mitotype in the egg Right the the egg that the mother carries and you know releases from the ovary. There's about half a million mitochondria in that egg 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 And one way we think about this is I think it's It makes a lot of sense to think about mitochondria as social organisms Hmm and there are multiple features of mitochondrial biology that obey, you know, what? A behavioral social scientist, you know classify as social, you know, if you study ants, for example There's like a few rules that we know ants are social creatures because 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 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 Active worker ant and then this like chubby warrior ant Genetically, they're they're identical They have the same genome they came as you know a little larvae from the you know the queen But they're they're morphology super different their behavior is very different but through development they're cues that you know are Uh Apply the two the different larvae and then they end up becoming a worker or a warrior So the same kind of thing happens in mitochondria. So might a there are different types of mitochondria like the two types of ants There is division of labor. There's some mitochondria, for example in the muscle that are at the surface of the muscle like just underneath the sarcolemma the The skin of the muscle cells and then there might a conglomerate or inside We are where the actin myosin the contractile proteins happen Sub- sarcolemma mitochondria and inter myofibrillar mitochondria two populations Their proteome is different or 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 differentiation of a mitochondria and in every cell mitochondria have a life cycle New mitochondria are born and old mitochondria die out Which is what happens in social creatures 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 Creatures then you 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 You got you brought one as a gift At one moment. I thought they might be brass knuckles when you hand it first handed them to me bites a mitochondria and with the cristae of the mitochondria There you go Usually looks like this but you're saying in in reality there'll be many of these connected to closely fused to one another 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 So if you're lucky enough to work in a lab That has one of these cool microscopes called confocal 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 like it goes inside the mitochondria It's attracted by the big charge that mitochondria have And then you turn out 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 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 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. Yeah We're building a web page called mitral life 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 not healthy and if they can't flow and transform energy properly they start to look really weird 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 All these discussions you should eat meat. Don't you eat? I believe you should eat some meat You should eat some vegetables some fruit etc. I think you'd 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. Yeah, 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 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 for today but I think if nothing else that people can just understand that they have not just these power houses But these power plants within their bodies that are transforming the energy and the mitochondria are central to how the energy is transformed and distributed on an organ by organ 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 a unit of you know heat off but 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 detail and aspects to that today So I just wanted to frame that up. Yep. If you have any reflections on that grade if not It was just a point that came to mind. 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 physical physical stuff remains, but 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 thinking 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 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. I think could be useful Along those lines. I I do want to um talk about this recent paper that you uh published 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 We'll 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 weight lifters 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 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 is 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 would love that we flow as energetic processes right to you 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 And we know exercise training is a beautiful example Like if you're trained to run a marathon for example, you can double the number of mitochondria in your muscles double right and My understanding of this is as energy flows through the existing mitochondria You're basically bringing your energy into that that system and then this That the biochemical energy gets transformed into molecules into metabolites and then eventually into proteins and then structure gets created as energy flows All 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 the resistance, it's that's when we build that's when we grow that's when right arnold schwarzenegger said Muscles are torn and in the gym they're fed in the kitchen and are A grown in bed I think is In an austrian accent yes, yeah, so 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 the the burning pain of and then when you let go is when growth and You know building can happen 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 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 muscle doesn't contract anymore You're basically blocking the flow of energy there and what happens? the atrophies right atrophy is a normal Movement of life when energy flow decreases and if there's no energy flow 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 Then naturally, you know that that area should Should grow and and build 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 A coping mechanism to eating too much But then eventually the systems like it gets overwhelmed and then that hurts the mitochondria and it hurts You know cells they 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 or energy? uh consumption energy transformation and then like sleepless and you know Work out three hours every day and then 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 and they're Yeah, we don't really know why that is why there's a limit to that and 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 tour de france Right like three weeks you're you're going for like five seven thousand calories a day You do this for three weeks. There's a reason why the Tour de France is not four weeks and five weeks Right 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 look at that curve, you know the the first point Max power output you can develop over 10 seconds is what you see in the hundred meters sprint, right and then you get the Uh 400 meters and and then it goes down at the very end the Tour de France is you know Marathon is here Tour de France three weeks is here. Then you get like crazy running across America multiple weeks And then at the very end nine months pregnancy And it costs energy to grow a human being and uh some of the data suggests That when you grow a human being for nine months Your base the woman is basically operating at the max of her capacity if you integrate over, you know a nine 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 uh adaptive to start to think about the world a slightly different way and that's not just just about yourself and um, so there there's certainly And even long lasting brain changes happen 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 menses, right? I'm in oria And this is not because the the reproductive system is broken or because the ovaries are or sick or something like that The best explanation we have is there's a shorter a 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 fuel 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 are all these theories, you know about do you feed or starve a cold or flu and I cover that in a different episode I will put a link. It's not straightforward, but um Follow your appetite stay hydrated keep your electrolytes up and so forth Yes 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 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 And I had a personal experience of this Over a new year is a couple years ago where I could feel I was you know coming down with something 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 oh, this is such 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 thought like just the thought of like grabbing my computer Then I thought 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 Motivation right zero My capacity to be the best human being that that I am and to be kind a little diminished Just like I was just Trying to fucking 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 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 forces you to put covers or you know to to dress to avoid cold environments Uh, you it hurts to move your body like to contract muscles and like this there's aledinia, right the sensitize 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 Cost energy nothing and biology is free Everything costs something and if you eat food now you need to masticate you need to like have Parastalsis you need to have gastric acidification movement, you know secreting digestive enzymes and be some bio like they're the The orchestration of digestion is pretty expensive. It's like 10 15 percent of your daily energy budget So that's a 10 15 percent 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 slash huberman to claim a special offer Just go to drinkag1.com slash huberman to get started You mentioned that if women exercise beyond a certain threshold, uh, they stop menstruating And that it's because there's not enough energy essentially to menstruate 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 menstruate 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 uh, you know, I'm not a computer scientist, but You know enough about Programming, you know an engineering that you know this concept of an AND gate 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 AND gate You need both things basically So I now and forever going forward will think about mitochondria as not just energy production, but energy distribution organelles 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 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 You need to eat you need to suck. No, maybe not. Whereas if I do have an appetite I don't care what people say about feet of cold starva flu or feed, you know starva flu feet of cold I'm just going to do what my body tells me to yes. Yes, and I agree the body is wise animals who don't have a very other non-human animals like your dogs like They they don't have a mind to distract them from you know living An alignment with their energetic states. So when they're sick the immune system just 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 So what where's that energy coming from? So not contracting your muscles because you feel it in pain is a good way not having to thermoregulate 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 energy conserving 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 our love handles The record actually for not eating is from this 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 pounds. I think So that's a lot of 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 energy the neural energy Do you want to do a little experiment? We can do a little experiment to feel our energy. Definitely. Yeah, okay By the way, uh A tenured 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 You know the reason things have happened in the world, okay The reason we both close our eyes and kind of stopped moving 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 proprioception 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 It will talk more about some incredible results about meditation and restoration of energy Can the audience do this along with us provide they're not driving? Yes. Yes. Okay, great 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 process. We'll take one breath in and then, uh, We'll we'll hold our breath for a little bit. So breathing in 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 that's urged to breathe and this desire to Bring oxygen into your body to your mitochondria And then when you need to you take a breath in you can open your eyes if you can't hold it longer you you know, yeah Where did you feel? So when I went to the full exhale and held my breath uh my What we geek speak what neuroscientists call interoception my perception of things from the skin inward became more salient and I could feel my heartbeat 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 on 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. Just fortunately sense of urgency and then with an with an inhale there's a a relaxation of of that sense. Yeah, and um There is the sense that uh energy moves out from the center at that point like like you'd feel more of your body Because I think anytime we don't have air Our brain goes to how do I bring air right here right now? You're not thinking heartbeat. You're thinking yes get get air. Yes 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 too many people dying by drowning or like suffocation is like the one of the worst death and 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 or at risk of Seizing to exist Not being able to breathe right being out of breath is an existential threat to your energetic self Without getting into the details. I've talked about it on another podcast. I had a scuba diving Accident a few years ago 2017 ran ran out of air and uh 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 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 terrible even though it's just a moment a moment The sense of urgency that kicks in is very intense and very very fast Uh, which speaks to just how hard-wired these circuits are because at that point presumably There was enough air to stay under for another five seconds or whatever it is But when we anticipate getting oxygen and we don't yeah, there's a big increase in stress energy goes straight to whatever whatever areas of the brain amygdala and other areas presumably that are like This is a bad situation do anything and everything becomes about resolving the situation Yes, and and that's because we are energy. We are the flowing energy through the system and if energy 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 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 a vaikido 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 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 Bazzillion 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 sing when people 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 A 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 Pottery we get a different brain then 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 exercising and I like thinking so Is there a trade-off? Is there a trade-off? Yeah, 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 hypertrophy to some great extent in some other area human 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 Exactly, but we did a study recently that points to the fact that there might be trade-offs Between different systems. Sorry meatheads. 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 tested the hypothesis that if you have more mitochondria in your muscles You also have more in your brain and in your heart and in your liver and in 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 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 Which is which might be what has led you to do what you do now right for with most of your time Because it's this really taps into your strengths. It really moves you. I suspect energetically I think I enjoy it. I did 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 people's genomes They're 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 appears to bring them energy and what this means biologically the whole of mitochondria I think 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 ask people or colleagues in chicago ask people before they died Like how do you how much sense of purpose do you have in your life? How meaningful social connections? Well-being right and then the negative stuff depression loneliness, you know anxiety 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 cagolin trump A researcher who works in our group who's a bona fide mitochondrial psycho biologist So she asked questions between the psyche and and the biology of mitochondria So she asked could it be that how people fell before they died? relates to the binocondria in their brain in the prefrontal cortex the DLP FC the dorsal lateral 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 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 rad 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 Sandi at EPFL in Switzerland that showed this 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 they're in some brain areas There are fewer mitochondria and they don't transform energy as well. So the mitochondria 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 we want to talk about the philosophy of this thinking about like what's causing what maybe isn't 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 Primarily is how we feel how we experience the world Somehow is related to the biology of the energy transforming units energy processing units interbrain And and maybe also in an 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 brain and muscle 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 I'm so glad that biologists like you exist. I just want to say that 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 Anything 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 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 confused like drama and friction with certain people is like that's energy expenditure. That's not That's not a 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 on neurosciences now You know or 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 by medicine right like many years ago 50 years ago or so like there was this wave of whoa 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 on the microscope and we can you scan the brain and like all of those 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 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 And what you really care about so like Pushing aside which is what biomedicine is done pushing aside the mind and all of those subjective experience. I think it's been really um damaging to understanding the basis of health and Understanding what allows some people to be healthy for like really a long time and to live long healthy lives and to live, you know fulfilled lives 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 who stuff and and we can't access this with bioma like your science and I think it's true I I'm not 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 this point that will 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 the molecules and the metabolism that support this flow, but as the flow itself I think that is kind of a point of conciliance energy flow is the linchpin between matter, you know the stuff of biology And experiences again, we don't experience energy itself. 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 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 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 conciliance point where we have you know behaviors Uh everything we do in neuro midging, right the eeg or whatever every 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 epigenome because of metabolites and whatever intermediates are there I'd like to take a quick break and 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 They've also recently added tests for toxins such as bpa exposure from harmful plastics and tests for PFASs or forever chemicals Function not only provides testing of over 100 biomarkers key to your physical and mental health But it also analyzes these results and provides insights from top doctors who are expert in the relevant areas For example in one of my first tests with function I learned that I had elevated levels of mercury in my blood Function not only helped me detect that but offered insights into how best to reduce my mercury levels Which included limiting my tuna consumption I've been eating a lot of tuna while also making an effort to eat more leafy greens and supplementing with nac and acetylcysteine Both of which can support glutathione production and detoxification And I should say by taking a second function test that approach worked Comprehensive blood testing is vitally important 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 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 function health.com slash huberman function currently has a waitlist of over 250,000 people, but they're offering early access to huberman podcast listeners again That's function health.com slash 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 Great neuroscientist at uh now at NYU once told me that uh 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 there are metabolites that are mitochondria producing based on the energetic state of the mitochondria there'll be more you know acetyl coa and citrate and uh lactate and alfakito gluterate 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 epigenome And now the cell all the sudden has this gene turned down turn off or this other gene turn on and now the cell is a different kind of cell Because there was a change at the energetic level in the mitochondria 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 cytokines and so cytokines in many ways or Signatures of an underlying energetic state. So what we call inflammation? My understanding 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 are not breathing Then you're like 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 cytokines come in Yeah, cytokines are you know universal language of cell cell communication cytokines are not immune There there's this you know fundamental way that cells have to talk to each other Assuming that it is this a repeating set of principles 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 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 jimmy hendrix and you know, she has joplin and there are others I don't know if they're all in the 27 club But I believe so and there are others but this idea that for people who's quote unquote flame burns really hot They're their intensity, you know their charisma early on They tend to die young and if not at 27 there are a lot of examples of this If you look into these different cases not the ones I just mentioned You often find that there was amphetamine use and you say well like what is amphetamine and cocaine use really? Well, taps in the dopamine system the epinephrine system. This is definitely the stuff of energetic deployment and release and transformation like these are not drugs that subdue people these are drugs that energize people And it's as if really there was a lot more life packed into a shorter period of time and they die early In a parallel vein I once had a conversation with someone that I understood Was a child prodigy and he stopped me at one point and he said no former child prodigy And I thought okay, we're being you know kind of detailed here, but I want to start reading about child prodigies You know, you don't meet many adults that Are brilliant Who continue to get brilliant their entire life more and more and more and more brilliant in other words child prodigies eventually plateau They just get there a little earlier and in some cases a lot earlier Have you ever heard of somebody graduating medical school at 16 and then becoming the best physician in their field? Continuing into their 70s and 80s. No people caught up people catch up to prodigies And so there's this idea perhaps that you know the Allocation of energy when it's really directed in time and in space to certain circuits of the body We see incredible feats I'm like, whoa But then it doesn't continue forever And I'm going to bring this around to this concept of longevity in a moment But I'd love your thoughts on that and then I'd like to talk about how The things that all of us can do can keep our mitochondrial reservoir high enough so that we can allocate it in different directions, but just curious your thoughts about people who Seemed that their their fire burns really bright and then it goes out early and prodigies seem to Channel all their energy into phenomenal things and we're delighted by like the you know the little the doctor who's 16 or the Person who graduated law school took the bar at 17 or something Then you look later and they're doing interesting things, but they're not phenomenal later in life people caught up There's a parallel in biology, which is how different species develop much faster Then they reach real reproductive age much faster and then they die much earlier Much, you know earlier like mice for example, they live like two to three years and they developed really quickly Um So the everything is like accelerated and there's two beautiful papers one published in nature one published in science on the same month in 2023 That I think shed some light on this they ask what controls the pace of development? In mice and in humans and so they took mouse cells human cells themselves put them in a dish and then you look for like the rhythm of development and they found that as Others had seen before the mouse cells which came from an animal that Develops grows and dies in three years versus human cells right an organism that develops grows and dies in like 80ish years Have very different different developmental rates and then they ask what's different between that? what controls the pace of development and they found that The main driver of this and then they did experiments where you can accelerate or decelerate the pace of development by Modulating mitochondrial metabolism and when you say mitochondrial metabolism is it fair to go back to the analogy of the morse code? Thing where the animals that develop quickly and die earlier It's like a faster transformation of energy exactly and that was regulated by nad I think a few people who listen to this know about nad and so nad seems to be kind of a dial on You know the the raid at which energy is transformed so interesting. I um long ago I was getting frustrated because all the discussions in the longevity space We're failing to acknowledge. I'm a developmental neurobiologist first what uh That Development is the most rapid period of aging ever look at a kid at one versus three. That's a lot of aging We don't think of it as aging because they haven't peaked in terms of their vitality and their maturation yet look at um Somebody before and after puberty. Mm-hmm first of all completely different organism of any species, right person Different personality much more, but it's it's probably the fastest rate of aging we ever undergo And so I had this theory that I'd love somebody to test maybe you're allowed to do this uh If you look at the rate at which people acquire secondary sex characteristics going through puberty Typically they they acquire one or several all at one at one stage and then it continues How long the the acquisition of secondary sex characteristics carries on Essentially is a measure of the duration of puberty because it reflects a bunch of changes in the hypothalamus We know that and that it cascade out to the body hormones and so forth I knew kids in in junior high school who we went away for a summer He came back and there was a kid on my soccer team. I'm like that's a grown man Like he had a beard and he but I won't mention who this is and he was very like muscular and lean and And he would score like nine goals every time he went to the more advanced soccer league and stuff I saw him in my 30s And I was like wow he is and there's no there was no envy or upset about this You know or schauldenfreude or anything. I really like him as a person. I was like, well, he looks like he's like 45 He had aged much more and then I knew other people that had that they kind of matured more slowly and Sure lifestyle factors play in here, but they were developing in a way as adults where you're like, wow They really like taking great care of themselves But speaks to this idea first of all that maybe the rate which one moves through puberty is predictive of lifespan Plus or minus some lifestyle factors Um, so what are your thoughts on that? Is it is it conceivable? I think it's conceivable And there's nice data on energy expenditure. How much body how much energy is the body burning? To go through whatever it's going through and again nothing in biology is free That's kind of one of the basic energetic laws of life Everything costs energy and in development you see when babies are born They're a little hypo metabolic. They don't burn as much energy as like an adult per You know kilogram or pounds of body weight, but then within within like a year You see this massive increase in energy expenditure And then it kind of peaks around five years of age when kids are like Developing so quickly my son is six years old and he's learning so much changing all the time so energy expenditure is like Peaks around this time and then by 10 15 years old It's you know around back down and then by 21 ish it's adult and then it's a flat line for the rest of the of adulthood Then around like 70 years old you start to see this this decline. Yeah, it's a myth that metabolism slows as we age I mean, it's true that if we don't up you keep our muscles and movement, etc Breathing yes, um exercise a lot of it is just breathing As bringing oxygen to your mitochondria as a friend who's in the incredible shape What once for me I said, what's your workout regimen? He's in his 60s. He's in a fantastic shape He says I make sure I'm doing something every single day where I'm breathing hard for one hour And I said, what do you do if you're trapped on a plane? He's like I breathe hard for an hour Former seal team guys, so they're a little extreme but you know, he makes a good point but The idea is that that we understand from this paper published in science a few years ago that metabolism Basal metabolism doesn't change much as we age. We thought oh my metabolism slows. So not true Once you hit adulthood, what once you hit your 20s, your metabolism is not changing much at all I think as you pointed out until ones 80s. Yeah, it depends at what level you look at metabolism If you look at the cellular level, they're I'm referring to the caloric Basal caloric need how much energy you need you should consume to Minus basal metabolic rate like minus your The the running the lifting etc that you do now, of course lifting can add muscle which then raises your basal metabolic rate but Just this idea that oh my metabolism is slowing as I it turns out to be completely false People have used as an opportunity to write off. They're overeating. They're over consuming energy in most cases. Yeah We've developed a model called the energy conservation model the the brain body energy conservation model aging the BEC model And so you could dive into this But I think there's significant changes that happen in some cells As cells age they start to actually burn energy faster when cells become senescent They burn energy faster and then they're sending signals I'm struggling energetically speaking and that's what I think inflammaging is You have some not all cells some cells in the body. They're kind of over the edge. They're becoming senescent And then they send signals and those signals are the same signal that we release during sickness behavior If your immune system is like really struggling energetically because it's trying to fight off a virus It's going to send those same cytokines and when those cytokines reach the brain the brain says oh shit We're going to go bankrupt. You know the energy budget is is threatened here So let's save energy and then you become apathic you become cold you shrink your muscles and those are all good energy saving energy conservation strategies To a viral infection, right? The same thing seems to happen slowly as you age If you have those cells that are sending those signals But with your exercise and if you don't eat too much and once in a while you feel hungry maybe intermittent fasting or Like you actually now can get rid of those signals of like energetic stress and you can Make the organism more efficient. I think a significant benefit to exercise is improving efficiency and then Then you can you know fight off inflammation really what this is is you're bringing the organism's energy resistance The the the cells that are struggling you're kind of normalizing them and then you don't feel like you're running out of energy So I think it's a perception problem so I'm now going to imagine that one of the reasons why we have less energy In quotes, uh, we feel less energy and we feel less energy. Thank you as we age is because of inflammation in the body Calling More energy to be allocated to those cells That are in the inflamed area and they're consuming more energy. So by reducing inflammation You have more energy to allocate to other things. Right. Got it. So this is very different than How we were talking about at the beginning when I said, you know, my advisor came up to me. Why do we have less energy? I just imagined it was rundown of mitochondria So this is what creates a kind of dynamic tension And that's very practical for for me and for everybody For instance, I could run more to increase the number of mitochondria in my body I can Sleep a little bit more to offset the inflammation from the running But ultimately I'm playing a game. I have to budget am I going to exercise more to get more mitochondria So my brain and body have more energy But I'm also going to create some inflammation when I exercise and that's going to eat up a bunch of energy too So it's just like time or money or anything else. You can't do everything. So You know, my mindset has always been and I think I'm going to stick with this, frankly Lift weights three days a week do cardio three days a week rest completely one day a week Do the other things like sauna and cold as you see appropriate but Make darn sure you're getting six to eight hours of sleep each night. I've been pretty religious about that for a long time and tried to not burn energy on Drama or mind numbing things and certainly don't use any substances that use up a lot of energy excessively I do drink a lot of caffeine but you know, like prescription stimulants that I know people rely on a lot like I'll just call it out modafinil. I've taken it once when sleep deprived You feel as if you slept eight hours, but you're borrowing that energy from someplace and It's not just the crash that happens later. It's the long-term effects of this and I think this is why people who use Amphetamines and and cocaine and things like that stimulants We often find that sure they die of heart failure. That's very common actually people who use cocaine earlier We're gonna talk about this, but let's just be direct about it. They're borrowing energy from the future Is what you're doing? Yeah, and so I think I'm a big fan of people exercising more eating better, etc But at some point you're increasing inflammation that way as well inflammation Is a reframe that to me completely changed my perspective on what inflammation is Inflammation is an energetic signal If you there are cytokines in your in your blood It means somewhere in your body and that's not true of like all cytokines But the major cytokines that we think about like il6 interleukin6 It's secreted by muscles Not during the exercise like you're doing your run, right? That could say you run intensely for an hour or two hours il6 has an increase. It's when you stop exercising Boom, you get this beautiful spike of il6 and then you ask what is what is that? So il6 is a cytokine, right? It's a cellular signaling system And then il6 goes to your fat and then it says we need energy like lipolysis chop out those You know lipids that's stored in your fat release that in the blood because the liver needs it to make glucose And then the il6 goes to the liver as well and then tells the liver make glucose because the muscle is depleted Right and the il6 burst after exercise is particularly strong if your glycogen depleted Right if the muscle is out of its internal like after resistance training or sprinting or high intensity training high intensity Yes, uh, so then the il6 then is a signal right to mobilize energy It's the muscles way of telling the rest of the body. I'm running low on energy, right? Please help and then it recruits the fat it recruits the liver and then it sends signal to the brain The brain has il6 receptors as well and it says, you know feel like crap like you need to recover Lose your vitality your vigor at least for a little bit And rest and like you know Arnold said you you become stronger you make your mitochondria more mitochondria And you become fitter not during the exercise. It's during the rest period. So so you know the getting sleep six to eight hours definitely And about stimulants like caffeine Uh and other stimulants what they do is they prevent you from feeling energetic stress So if energy is not flowing properly in your body and you should be sleeping to kind of decrease that energy resistance Uh, then those stimulants kind of make you oblivious to those signals And now they're clinical trials in which I think are potentially dangerous that are happening where Those drugs are being developed antibody based, you know drugs to prevent the brain From feeling signals of energetic stress in the body. That sounds like a terrible idea. Well, if you think about this simplistically and you know from You think the body is a molecular machine you think here's what's happening when people are sick to have cancer, right? Gdf 15 just growth differentiation factor 15. It's which is a protein. It's a cytokine It's secreted by cells when energy can't flow properly in mitochondria. So if the cell is burning energy faster than it can sustain Uh, it will start to secrete gdf 15. So people with cancer Who end up developing catechia or their muscles? Melt away They tend to have very high gdf 15 and then gdf 15 can go to the brain and uh as far as we know The only place or as far as the the community believes the only place where there's a receptor for gdf 15 is in the brain But the brain doesn't make gdf 15 Gdf 15 is made by every other organ in the body including tumors So what happens is that people with very high gdf 15 feel terrible And if you actually inject gf 15 into an animal to ask what does it do? Like what does gdf 15 mean if you have a lot of it in your blood? Well animals actually puke And it caused you know an aversive reaction. Uh visceral malaise is the technical term So you feel like shit gdf 15 which is produced by cells Struggling energetically and anywhere in the body Signal to the brain and makes you feel like shit. We know now also gdf 15 is the trigger for morning sickness In pregnancy. So the reason you know, uh, women, especially Hyper emesis gravitarum hg which is like terrible women who have this Many of them want to terminate their their pregnancy. It's so horrible. Like if if gdf 15 rises like 10 000 fold There are not many, you know hormones that can Increase that much during pregnancy the placenta sends out gdf 15 maybe to tell the mother like chill out Reallocate your energy. You're growing something that is costing a lot of energy So we know gdf 15 does this. So now what pharmaceutical companies have tried to do is to say, okay Let's block gdf 15 signaling so people don't feel like shit Uh, and so there's this one trial that was published in the new england journal Last year and they show as expected if you block gdf 15 with a monoclonal antibody People don't feel as terrible and they eat a little more and they don't lose as much weight Right, so it's basically if you're sick in the hospital, you have cancer. You're getting chemo You don't want to eat right and energetically I suspect this is the right thing to do because you're saving 10 15 percent of your energy budget Reallocating it for to healing processes your immune system whatever the body needs to to survive that challenge Now you're kind of depriving the brain of that signal. So people actually don't lose as much weight So then that trial said success If you look, you know, a defined print and you look at the table where they report mortality mortality was double In people who were receiving the drug That trial was not the powered to detect Mortality as a primary outcome. It was, you know powered to detect changes in body weight So So that that didn't end up being a main finding but if this is real right You're preventing people from losing weight and they feel a little less nauseous But there's twice as many people who died during that trial Because the body is smart and it knows to not allocate energy to eating under normal conditions to normal There's nothing normal about chemo conditions But I think you understand what I mean that that the body's intuition to not eat is smarter than any kind of You know molecular A chicanery to to overcome that signal and have you be hungry and you would think oh, they're getting more nourishment They should more of I thought you're gonna tell me that more of them lived You're sending me twice as many died died and and recently there's another trial Large-scale trial for heart failure That looked at this using this antibody to block because when the heart struggles dilated cardiomyopathy or congestive heart failure Energetically, it's really demanding for the heart to be pushing against high blood pressure or to be failing, right? So there's an energetic stress in the heart at that point gdf-15 goes through the roof So now people know in cardiology gdf-15 is a really good marker of heart failure and then The the thinking I think our way of thinking energetically, but gdf-15 is a little different than what the rest of I think the field Things that people see gdf-15 as a marker of inflammation And then maybe that's like immune or I think it's a marker of energetic stress the heart is calling out for help and trying to kind of Calm down the rest of the system, right and by signaling onto the brain turns out many more people developed Heart failure and like adverse events Under the drug so they start the trial where you block gd-15. Yes So if you block this is the danger of of molecular thinking of everything in terms of receptors and and ligands Like the things that plug in people might not know what ligands are things that plug into the receptors and activate them I mean, I love modern biology and there's a lot of beautiful things but but the The systemic effects are heart are impossible to predict. I guess that's why you run these trials I do have a question as it relates to this Which is a big theme of your work, which is about stress Well, I'm sure people are wondering by now tell us about the gray hair reversal. So let's start with that Let's just get that out of our systems. I will say Despite some some theories not that anyone cares that much. I've never dyed my The hair on my head. I do have some grays, but the the number of them waxes and wanes with how much sleep I'm getting It's kind of interesting Perhaps but my beard's gray, right? And I'll tell you I'm not sure that all gray can be reversed by just reducing stress But I don't dye either my hair or my beard. So I'm a I'm a natural experiment in this. Yeah 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? Mm-hmm Likely both are true. Yes. Okay. And I think what we discovered is that Hair graying at least temporarily is reversible And 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 hallmark of aging Which is you know deep pigmentation losing color and your beard and your hair Um, it's 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 like you have every hair on your body is about 100,000 hairs on your head Uh, 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 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? Like if I thought if we could figure this out The the basis for the heterogeneity, right the hair to hair heterogeneity Maybe we can understand why different people age at different rates Uh, because it's very clear that there's no more than 10 percent of how long you live that genetically driven Like the best studies put this at around 7 percent 7 percent of of longevity is genetically inherited. Maybe and then about 90 percent is not is lifestyle factors lifestyle You know food exposures like, uh, whatever whatever is non-genetic people will take solace in those numbers Yeah, I think those are really powerful numbers, uh, and they surprised me because I had learned You know through my uh training education that uh, the majority of of how long you live is is you know, your parents and I think this is legacy It's like dogma. Uh, it's not science-based. It's dogma from, you know, the human genome project era like through the 90s We were hoping we would find the gene for cancer the gene for heart failure the gene for Alzheimer's the gene for schizophrenia and then the human genome was sequenced 2001 and then there was like 10 20 years of GWAS genome white association studies trying to find People who have this disease and trying to find which gene do they have that other people don't have right those large-scale studies and if the If the human genome project and the search for causal genes for common chronic diseases Had been an rct It would have failed its primary endpoint I think if we're real about this the The hypothesis was wrong. It was it was a useful hypothesis like many hypotheses are It led us to you know, learn a bunch and the human genome the sequencing that was such a Such a driver of progress and biomedical science But it's failed to solve the the big mysteries about why we we get sick when we get sick No genes will tell you this. Yeah, I would say the human genome project like so many things the brain connectome Proteomes inflammatory tomes Necessary but not sufficient. Correct. We want to need the information, but it's not sufficient to demonstrate anything except It's a hypothesis generating experiment. Yeah, I know I know this because I sat on grant panels for a long time and You look at these incredible studies like we're gonna measure the difference between this cancer cell and that cancer cell in this and it's great, but The information you get is necessary, but it's it's not conclusive of anything But it is good work. Yeah, it's good. Of course. It's good. There's a lot of really high quality science, uh, that's happening But I think in general academic science has kind of lost track with its core purpose And now we have like an incentive system and there's a lot of forces at play in an administrative You know processes that don't serve the the primary angle, which is it's all getting revised now. So It's uh for for better or worse. It's all getting revised. So I see your point. Um, I'm Um Warmed by the fact that even though my parents are still alive and are doing well. Um, thank goodness that only 7% of longevity is dictated by the genes. Uh, so if you have parents that lived a long time, this also means you got to keep Upkeep is important. Um, but what you do is is key. So Um, so with respect to Look graying hair isn't the most important problem. People can dye their hair Right if they want to uh, people can shave their head if they're losing hair Like there are a bunch of ways around this monumental problem of graying hair But I think what it illustrates is really interesting. So, um, but it's river that it's there's plasticity. Yeah So could you explain the result? So, um, when we started to think about this We thought what if we found hairs that have like the same hair has two colors right, so you have a piece of Of a segment of the hair that is dark and then a segment that is white And then if you could find a hair that was dark so the tip Uh, the tip of your hair, you know used to be inside the body. Yeah Just like it's it's a bit like tree rings Right if you cut down a tree and you look at the tree rings You can basically go back in time and say oh 20 years ago. There was a fire here, right? And then 45 years ago there was a drought and you the tree rings look different and so there's information encoded in the structure, right? So we all walk around With kind of a molecular record like a physical timeline of our biological history because stressed relaxed good relationship bad relationship Yeah, so if and hairs grow writing a grant after the grant That there was actually part of the data for that study I was one of the participants early on because we became interested in this we found a hair that were two colors Two colors the tip was dark and then the root was white and then we thought oh if we can like figure out That hair transition and then if you measure it and you know how quickly the hair grow Then you can say okay two and a half months ago, right? Then you can look at the calendar and say about here this hair went from being dark to being white What happened in this person's life, right? So that was the idea and then Back then my partner uh went to the bathroom and then she she brought back like she had very long hair and then you could see like Clearly the same hair two different colors It's like shut the aging hair grain is is there's plasticity here and then we found hairs where the the hair was white and it went back to being dark and This was a little confusing and then we had one participant who brought a hair A young asian woman and her hair was so beautiful It's just she had like really dark hair and then the root was dark And then there was a segment two centimeters But like almost an inch of of white and then the rest of the hair was dark again What happened in that two centimeters? Yeah, exactly. So that became the the question. So then we developed we said, okay We need to do this quantity to tell you what had happened She we were collecting hairs and ziploc bags. So now people started to mail us, you know ziploc bags with hair Um, uh, and we got some hairs from friends hairs from from Canada from different places in the u.s across body regions in south asian african-american, you know, uh, white So it was clearly real and then we said we thought we need to develop an objective semi quantitative method to Quantify stress because we quantify now we we bought a scanner, you know old style like photo digitization system So we bought one of those high-end scanners and then we could iron out like a single hair Tape it down and then like scan at super high resolution So then we can get like a digital Readout of the hair like tree rings and then you could see okay. The hair was dark and there's actually information There's like it looks like eeg almost but we're looking at hair color and then it lose a lost color So then you can say okay, this is the point and then we needed something similar for psychological states right what happened in this person's life Ideally you would get blood or saliva or something else But uh, we could go back in time with this and then I sat down with this participant and said okay This is now and this is a year ago Uh, and then you can look at your calendar. What was the most stressful part of of the past year? And then for her it was you know very clear and then what was the least stressful part of the last year? And then people would rate this there's the y axis is most stressful at the top You least stressful zero at the bottom and then they put points and then connect the dots right with the line So then you end up with a line graph of someone's you know recall of their stress levels anchored in some You know objective life events. So that was the methodology we use and for her Uh, and she she had sent us the hair a few months ago and then you know, we were doing the the interview And her profile was so beautiful and she said I had submitted my thesis. She just graduated her phd on the at Stanford actually and then uh, she You know had a chill summer and everything was okay Then she had some issues with her boyfriend and they broke up and then she was like in crisis What do I do with my life? Do I you know get this job or that job? She had to go to europe for some family issues uh, and then um And then she ended up moving to new york city getting a job reconnecting with her with her boyfriend and then life was great And her graph looked, you know, exactly like this and and that period lasted two months And it mapped to the gray zone it mapped Surprisingly perfectly with the with the the graying right where the hair lost color So it was the hair the stress peaked for two months and then came back down She said these were the most stressful two months of my life super interesting Um, and that the papers got a lot of press as it as as it should be I've received about 300 emails since that paper was published People for sending me pictures from all over the world saying like I found this this two colored hair I thought I was crazy Google this and found your paper when I was growing up my dad told me that he had a cousin who Uh worried so much that he went to bed one night and woke up and all his hair was on the pillow And I didn't know until I was an adult that that story was designed to get me to stress less And then it wasn't completely true. Um, but that's hair loss not graying, but Is there any graying of hair beard hair or head hair? That is just simply related to age or can we say that any graying of hair that's age associated Is likely to be associated with the increased inflammation that comes with aging A.k.a. stress a different kind of stress not psychological stress Yeah, maybe depends how we define stress we define stress as anything that cost energy Well inflammation cost energy is inflammation cost energy and making a cytokine cost energy And if you're a cell and you have a receptor for A cytokine and the cytokine dogs the ligand dogs that's going to cost energy It occurred to me that when based on what you've told us that when we're young we need a lot of energy And we don't want kids to overeat but they need energy and their levels of inflammation are very low Kind of a perfect situation for development as we get older We generally move a bit less Or a lot less, but ideally it's just a bit less Or maybe we move more and in general people need to eat less Not more as a rule. Okay, but there are always exceptions to that rule But there's a lot more inflammation. So we're actually much more energetically expensive Because of inflammation as we age And I'd be willing to bet that some of the graying of hair is related to the aging Inflammation thing. I mean my level of stress Who knows what it is because it's been, you know, jagged line for so many years I don't know what baseline is I drink caffeine like, you know, like most people We're masking a lot of the things that are going on but um, I love the results showing that increased stress graze hairs and reducing stress Ungrays hairs. It's a correlation. It's a really it's a correlation. It's a really cool result I want to talk about restoration and recovery of energy Maybe with the hair graying that I think what connects the hair graying with everything else we've talked about Is the analysis we did of knowing like molecularly what happened in the when this one hair goes gray And then it recovers its color What's happening energetically? So we took a single hair and chopped it into pieces and then proteomics You have to because you're a molecular biologist, right? And I mean mitochondria is is our way to tap into you know, the biology of energy So then we we thought maybe there's something there and initially I didn't think there was mitochondria in the hair turns out every hair that we walk around with is loaded with mitochondrial DNA And you know forensic if you find a hair on a crime scene you can figure out who is there The DNA that gets sequence is not the nuclear genome. It's a mitochondrial genome. Really? And because hairs have a very high concentration of mitochondrial DNA So you guys you can't commit a crime except to get away with it because if you leave one hair Martin's lab is gonna Oh, we don't know if we don't do forensics. Sure, you know what? The signature the molecular signature that was the most robust Comparing the white hair to the dark hair in the same person or comparing white to dark in different people was mitochondrial proteins And I would I did not expect that and we repeated those experiments in two different proteomics core, you know, there's The and the proteomics core hated that experiment because hair is like Notoriously, it's full of keratin those super high abundance proteins and and then they mask every other signal But we were able to kind of get Good resolution data for other non keratin non hair proteins and three mitochondrial proteins were consistently up regulated There was more of the mitochondrial energy transformation machinery In the gray hair compared to the dark hair love the direction of that result I don't love that stress increases graying But I love the direction of that result because it's yet another brick on the wall of what you're telling us that Stress is an energy requirement a commotion associated with aging is an energy requirement being sick Creates different energy requirements and we need to obey these different energy requirements fascinating So in terms of removing Or reducing metabolic demand in order to keep our system going First of course is sleep Right You were telling me earlier before we started recording that during sleep. How much does our metabolic needs Become reduced decrease. Yeah, most people know when you sleep your heart rate goes down and a bunch of your body temperature goes down and that allows us to go You know to to stay alive with 10 15 percent lower energy expenditure and that the They're different between different people But you know 10 15 percent is kind of an average of how much energy you're saving by sleeping And that there's a theory of why why do You know every add why does every animal need to sleep and if you sleep the private A mouse or rat or you know an animal you they die eventually And we know from like severe cases of mania and you know bipolar disease people can die from from going without sleep for you know multiple days So and that might be one hypothesis to because sleep saves or conserves energy and and if you don't go into that state of like Torpor right almost like hybrid mini-hybrid hibernation then you Somehow the organism can't sustain that and I we have some thoughts as to why this is I was reading recently about this lymphatic clearance of waste in the brain. Yeah, another that occurs during sleep and There was an interesting figure in this paper showing that every mammal Puts its head down During sleep and there's some cute pictures of panda sleeping on their side The giraffe apparently puts the top of its head down in order to presumably increase lymphatic clearance But I could also imagine that resting one's head reduces energetic demands. I mean some people can sleep standing up, you know against a pillar or something I've done that falling asleep like that a bit But in general sleep is a time when we want to rest our body and our mind And with the exception of rapid eye movement sleep when the brain is very active Sort of a reboot of sorts periodic reboot um sleep just seems like this beautiful way to allow the mitochondria to Either restore or you just you don't want to You can't out eat sleep deprivation either. You can't eat more to get more energy That's very clear. Yeah, that's a very important statement. Um Now I'm long been curious about things that people can do in order to either reduce their sleep need or I prefer to refer to it as increasing their vitality while waking And it is true. There are data showing that people who meditate For an hour or so per day or two 20 minute sessions Seems to be the most typically used protocol can fairly dramatically reduce their sleep need and really You know go from like an eight hour need to a six hour need with a 40 minute investment of meditation What are the data on how meditation reduces? mitochondrial function and energy use I want to start by saying we don't know what mitochondria do when we sleep like do mitochondria sleep You lose consciousness and the body, you know goes into this hypometabolic Restorative state and yes, there's lymphatics and you know, uh garbage, you know clear out in in the brain, which I suspect might have an energetic effect If you have garbage in the brain, probably the brain becomes less efficient So it needs to burn more energy to do the same thing So maybe the reason why the brain clears out stuff and why that's an important part of sleep is for an energetic purpose Right, so we're we just finished an experiment Where we had people come in the lab for 24 hours sleep into the lab and evan chelson A student in my lab is analyzing those data and I think for the first time we'll be able to know What do mitochondria do when you fall asleep and you go into this hypometabolic state and you're kind of conserving energy How is energy reallocated? So we see sleep as a two arm Process one it slows some things down if the heart beats, you know 10 times less per minute Like that's a lot of energy every time the heart contracts Right systole diastole both contraction relaxation cost energy and then if you do this 10 times less per minute That is a bunch of energy that can be reallocated redistributed. So, uh, we suspect that there's three main buckets of energy expenses That the the body needs to sustain, you know at some point in time one is vital You need to keep your heart beating at you know, your resting heart rate the brain function your kidney You need to be you know detoxifying clearing the the blood and all of your vital organs That's vital cost second is stress cost right if your sympathetic nervous system is activated because you're uh worrying about the future or you know worrying about the past or Like you're stressing yourself out this cost energy and then your blood pressure increases that cost energy heart rate increases cost energy You're sweating a little bit cost energy your hair rises, you know Anything that you're you're doing it will cost energy and then steal that energy we think from a third bucket Which is what we call growth maintenance and repair GMR And those GMR processes happen at the level of organs, right when you have an organ that gets bigger and stronger For example after you know weightlifting Uh, it can happen at the level of this a cell if the cell has your needs to repair its membrane needs to repair its DNA This will be growth maintenance and repairing if you make more mitochondria mitochondrial biogenesis after a workout That will be growth maintenance and repair uh, and because there's a A finite energy budget there's an economy of energy How much energy you have needs to be distributed between those vital costs the stress costs and the GMR growth maintenance repair costs So if you're stressing out all the time, we suspect this actually steals energy away from GMR And then you're not healing you're not growing you're not, uh, you know learning maybe And what sleep might do is actually shut down all of those stress processes When you sleep heart reverability increases, right parasympathetic tone increases Sympathetic nervous system goes very quiet. Uh, and then all of the stress related expenses Uh, then become quiet then that energy piece of the energy budget can be allocated to growth maintenance and repair Uh, and when you meditate, uh, and there's this beautiful study that shows expert meditators Uh, can go into you know a deep state where their energy expenditure goes down by 40% So 10 to 15 percent we said earlier that's how much you can save energy by just sleeping Meditating it seems and some uh trained people can bring energy expenditure down by 40 percent This is more than sleep. So they're able to shut down right or quiet down maybe vital processes Like we know the heart rate can go down extremely low probably stress processes We know this from measurements and meditators And then maybe that energy can be reallocated to growth maintenance and repair So if you do more of gmr and you're waking life because you live more mindfully and you don't stress yourself out Think about the future or the past or you know about Self-related thoughts Then maybe you're you're you can do more gmr During meditation or during your daily life and then you don't need as much sleep If the purpose of sleep is to reallocate energy towards growth maintenance and repair It's definitely been my experience. I I've talked before on the podcast. I'm a big fan of yoga nidra Or I coined a variation on it non-sleep deep rest You essentially consist of lying down intentionally staying awake and For 10 to 30 minutes and you do a progressive bodily relaxation while keeping your mind awake the reason it's useful is twofold one You emerge from it with a ton of energy mental and physical energy your vigor is restored even unless sleep The other is that it doesn't impede Your ability to sleep at night if anything it facilitates it whereas naps can often Create a sleep inertia you feel sleepy afterwards then people drink caffeine and then can that can cause issues Or just even make it harder to fall and stay asleep at night after naps whereas non-sleep deep rest Yoga nidra is very very efficient this way The other thing is that I've been playing with lately that I've found to be tremendously useful I sort of joke about this. I was telling my girlfriend the other day like um We'll just say for the hour or so before sleep To just like listen to music have the lights dim Just like really relax Or maybe the 30 minutes before sleep just really relax And it's almost as if I mean you're you're awake You're not asleep, but I notice that it Dramatically reduces my sleep need. I wake up from six hours feeling like I got eight And I monitor my sleep and so it's a pretty robust thing I suspect it's the slowering of the heart rate before sleep I suspect that's what it is because it's not actual sleep So you think it helps you get into deeper state of sleep faster or I think it's Restorative in its own right and it probably helps sleep as well because it's anti-stress and so you know, it's hard to tease those apart But I think this idea of Not just lowering the lights dimming the lights, but also reducing the heart rate as you head into You know getting ready for sleep, you know brushing your teeth getting ready for sleep You know and pre-sleep activities being very relaxing. We hear that for the de-stress component But I suspect that the brain is already going into a sleep-like state. Yeah, so I suspect that's accurate and um if you're by You know Creating that environment and then it allows you to relax right what relaxing means basically is you You decrease the energetic cost of sustaining your organism Then lowering heart rate, you know lowering cortisol in your blood, narp and effort You know catecholamines and the things that cost a lot of energy We've done experiments and cells in a dish you give cells Glucocorticoids like a cortisol mimetic or norepinephrine And then we want to know how much energy does it cost right to to mount a stress response Like those hormones are not damaging by themselves But if you give them to cells these those cells go into like a whole Choreographed response evolutionary, you know ingrained response that prepares them for the future Right, it's called allostasis and that cost a bunch of energy and we found it was about 60% So the this doesn't happen, you know in human beings, but if your energetic Metabolic rate increased by 60% right with glucocorticoids you'd be in big trouble So it might not be as much in the whole body, but we know now that Just a stress hormone on cells, you know in a dish human cells is able to increase the energetic cost of life So it it costs energy to to worry about stuff So if you can decrease the level of those hormones and decrease the level of cytokines in your blood inflammation That's going to save energy and then yes, maybe sleep is is more restorative And this the sleep study we did there are people who sleep energy expenditure, you know drops Significantly like 20 other people doesn't doesn't drop, you know almost at all In particular people whose mitochondria don't work very well So we've been so fortunate to work with patients and I'm not a physician, but I'm in the clinic half day a week to and I see patients that have followed now for about six years Who have genetic mitochondrial diseases? So they're they're pretty rare But they have a mutation or deletion in the mitochondrial DNA Some of them is in the nucleus nuclear genome, but it affects the mitochondrial energy transformation capacity Those people are always tired You know they don't feel well They avoid exercise at all costs because it just feels so terrible because their their mitochondria have increased resistance to energy flow So if you try to push more energy through it's really uncomfortable Gdf15 through the roof The best biomarker of mitochondrial disease is actually gdf15 Which you know tells us something about the Where what gdf15 means to the organism when the mitochondria don't work properly those cells that can't flow energy properly send out gdf15 as a signal And if you do a sleep study on those individuals and you look at how well do they? Decrease their energy expenditure to go into this restorative state the parasympathetic nervous system can't kick in so Some of the biggest difference we see between mitochondrial disease and people who have normal healthy spectrum of mitochondria is this inability to slow down and to go into this restorative state at night So that that positions mitochondria In in the context of restoration and you know the the ability to heal and And and lifespan and those people is decreased by about three decades As long as we're talking about sleep and meditation and lowering one's heart rate before sleep By whatever means you know We should talk about nutrition and exercise and supplements there I say And prescription drugs including the glps so I realize you're not a nutrition expert, but you think about energy You can't out eat a bad night's sleep But we all need nutrition it when you personally step back from All the noise around nutrition What are the key takeaways for for you in terms of how you think about optimizing your mitochondrial health and energy flow. Yeah, I think we've gotten things wrong for two main reasons One is we don't think about the individual. We try to find One size fit all solutions carnivore is good or keto is good or High carb is good or you know meat is bad or right there all of these variations which People feel really strongly about And this brings us back to like the value of the human experience Like you know for yourself if you try if you change your diet and it changes your life Like you have vitality you've you haven't had in like 20 years and your symptoms inflammation right Or is is gone and you have clarity of mind you've never had I've met several people now who've had this kind of life changing uh energetic shift happen when they go on a ketogenic diet and when they in store, you know intermittent fasting life changing shit So they know that that that this is real right and um, and then you do an rct and And it's okay. Let's test the randomized controlled trial. Yeah. Thank you. You do an randomized clinical trial and then what you do there is you feed everyone the same thing ketogenic diet or Standard mediterranean diet or whatever you know diet as usual And then people are on this diet for x amount of time 12 weeks And then at the end you compare whatever outcome you determined you decided was the right outcome And then you have like let's say 50 people here 50 people here And then you ask did the ketogenic diet? Improve mental health or did it reduce inflammation or right? Did it do that? and and then often in rcts for Dietary interventions or drugs what you find is not really maybe a little bit right and then if this the study was adequately powered And there's like an 8% you know shift and your primary outcome then it becomes p less than 0.05 The the p value the statistically the statistical You know Value here becomes significant and now you say oh the ketogenic diet is effective for this or the ketogenic diet does not work You know for for x This and this is I think highly misleading because when you peel the surface of any Randomized clinical trial you find that there are people who were like amazing responders Like there are people whose lives was changed truly And then there are people who Didn't change anything and then there are also people who got worse And then you average everyone you squish everyone into this average and then the rct is is a statistical test of averages Nobody is the average Nobody is actually the average literally literally and and then the ketogenic diet could literally save lives and it could cure Or be like a really solid treatment for schizophrenia or bipolar or or crone's disease or whatever it is For like 20 of the population And we'll never find out Just because we have a science of averages. Yeah, well a safe self experimentation is the only solution to them Yeah, it's the only solution. Yeah, and and that You know, there's a clash here between The value of the human experience, right? You know that this thing works for you and that you live at a higher level, right? You can fulfill your potential and then you see the science that you know the Capital s science that tells you no what you think it works doesn't work And there's no but it works for me and then you have a white coat wearing person Who says no, no, I have the authority I can tell you this rct shows that it's not effective and I think this really Is damaging like this it makes me angry. I'm I feel on cupra when I talk about this because This is a completely disregarding the human experience You know and service of this, you know framework that doesn't serve the individual that those the rct was invented for very good reasons and And it was it's very useful in some circumstances like do antibiotics work Should you you know be doing surgery this way or that way? But when you get to interventions or treatments that or likely to have a highly individualized Effects and there are people who respond amazingly to this to that then you end up disempowering people So I think there's a clash of I know this to be true from my experience And then I have this person in this position of authority the scientist or this doctor that says no this doesn't work because the rct showed That it didn't work like this is really this breaks trust and And so I understand the frustration of so many people who've lost confidence in in science and in the medical establishment I think for for good reasons in many cases. Is it fair to say that then there is no Best diet for mitochondria except the one that's energetically Not excessive not calorically calorically excessive. Yeah, so eating too much for sure damages The whole system Including mitochondria So the first piece of response to to your question is because we don't think about diet in individualized way We're missing the the boat on actually finding diets at work for different people So we're working on a platform that would empower people to Get some objective readout, right of energetically. How are they doing and then and then And a framework also to you know, we can all be thinking scientifically about our own health and about ourselves and once you realize you're you know, you are the flow of energy that Rushes through your body with different levels of resistance Then you can think about the food you put in your body is actually fueling that flow, right? You are the movement of energy and that is continuously fueled by You know what you put in there and then the By the the activity you do and the the kind of things you engage with So yes, we need a framework for this. We're working on that. So that's the individualized piece, right? there's very At this point, I'm pretty convinced there's no one diet that is our best diet for everyone I've seen people thrive on very different diets since we've been kind of working on related areas and And a few years ago. I received a research prize the bazuki prize and science Which was so enabling and a bazuki group as a family foundation Who's their son? was diagnosed with bipolar disease and and tried all sorts of Treatments and and drugs that you know didn't work very well or and you know actually made things worse And so they were on a diagnostic odyssey and trying to find something for years and then finally They came across a psychiatrist who was using the ketogenic diet as a treatment And so he went on a ketogenic diet and uh jan bazuki the The mom Said like I had my son back like within a few weeks. He's his mood, you know got stabilized. He was able to sleep and He stopped kind of you know cycling between mania and major depression um so for him like you know that really worked and uh so I was sensitized to that area of Of work and research and then dozens of other patients and I've met, you know, so many people now who Who managed their mental health disorder with? Uh ketogenic diet and they test, you know, their blood ketones to make sure they're still in ketosis And there's now a continuous ketone monitor ckm, you know cgm right so you can test your ketones I wore one for for a month and learned some really interesting things about my body and about you know, how were you ketogenic? I tried. Uh, did you like it being in keto? Ketosis I really enjoyed the state of ketosis and um And I think there's a reason why fasting is Uh a common practice in every ancient tradition and every religion has like a fasting component to them It puts the organism in this pro healing state right, which is probably why you don't eat if you're sick and uh Um and why animals also stop eating when they're when they're unwell. So it seems to foster, you know promote something Uh, and then I had much more, you know, better clarity of mind And that's what a lot of patients report as well. Like did you stay on it? No It's hard to maintain. It's hard to maintain and I didn't you know feel the need. I missed berries I avoid I know I don't handle sugar well. So I I ditched, you know refined sugars. Maybe like 20 years ago Do you drink alcohol? I don't There's there's good research When I saw that study like, oh my god, this might be why You know, I feel like shit the next day after I have alcohol or my sleep is not good or and why patients with mitochondrial disease Like the majority of them are very alcohol intolerant Uh and and then you know, you can make all sorts of theories about maybe it's like the detoxification enzyme and the liver and uh Like energetically dirt on edge, right? And then if you look at how much energy does it cost to get rid of the alcohol, right? It's a toxin So everything in biology cost energy. Nothing is free a basic energetic law of life So if you put alcohol in the body now the body has to you know, spend a precious Portion of its energy budget to removing alcohol and it disrupts your sleep. The data came out recently This was covered in the uh traditional press. I think you can look it up folks. It's uh, there's something like a 50% reduction in alcohol Consumption in the united states. Yeah. Now. I think it's the lowest alcohol consumption in something like 90 years Is it pretty spectacular? We did an episode about alcohol a couple of years ago. It turned out to be a very popular episode Um, uh, and there's a you know, the argument has been made by me Uh, but others now as well that zero is better than any and the upper limit for you know, sustained health is Before you start to run into some issues Is probably one or two drinks per week. But this idea that wine is good for us um There's been a reanalysis of that by Keith Humphries and others at stanford if you look at the way those studies were designed Uh, and he's coming on the podcast. So i'm not going to detail it now the the way those studies were designed was was poor experimental design all of it speaks to the fact that Zero is better than any And now that's not to say people shouldn't enjoy a drink every once in a while if they want to but they should know what they're doing Yeah, are you willing to sacrifice? 10 of your energy budget You know going towards alcohol detoxification Can you spare that at 10% if if you care about that 10% and you want your vitality or Then maybe you maybe you don't drink when I was going to a lot of scientific meetings You know, there's a lot of drinking that happens at scientific meetings. I would uh, take solace in the fact that I'm going to sleep relatively early 11 o'clock isn't that but I didn't stay out late And I wouldn't drink and I'd watch other people in my field that I was competing with stay out late drinking And some of them were more senior than I am one of the bigger labs and I was like, I'm gonna take your lunch I'm gonna take your lunch the competitive edge. Yeah, I'm good. I yeah that and I'd recommend that they watch certain Netflix series Because that'll definitely take your competition out. No, I I would watch people who are in the field of health and science Degrade their health in real time and it was perplexing to me because the amount of alcohol consumption anyway I'm editorializing now. It's bad for your mitochondria is what I'm getting. I think it Steals a piece of your energy budget. Okay, so whether you want to you know, allocate that energy if you have extra energy to spare You want to do that? But that's a good way to think about it in some cases uh, let's say you know Vital processes nothing you can do about this and as you age probably those increases stress processes Right the mind creates most of those and that is stress related energetic cost And then growth maintenance and repair if you're uh, for some reason circumstantial or you know, you have some some, um, we all have shit we from our paths that we deal with Uh, if if this is burning a big chunk of your energy budget, right every day You you're a little traumatized or you know, you worry about the future about your self image or whatever If this is burning, let's say 20 30 percent of your energy budget And when you drink alcohol that 30 percent goes to 5 percent, right? Uh, you're you're maybe wasting less than 10 of your budget to detoxifying alcohol But if you're relieving that's stress, you know, I suspect this is why, um You know, there's a people, you know, that really like their social drinking because it relieves kind of a A stress energy wastage Yeah, no makes sense. Yeah, no the the stress piece is huge and when you You've set up this framework for us, which I really really like about energetic flow as opposed to just energy coming into the system as a Key thing to think about and then how we allocate energy at the mitochondrial level But at the decision-making subjective whole whole person level Um doing things that bring us a sense of meaning clearly is energy building not just energy Expending although we can't take it so far that we're not getting enough sleep I mean, you know, there's always that the housekeeping that needs to be done of sleep and nutrition, etc I am curious about exercise You mentioned training for a marathon will double the number of mitochondria at most But where's the the sort of sweet spot of doing more exercise in order to increase mitochondrial density and etc efficiency Um, but not so much that you're robbing mitochondria from other areas of your of your biology that are critical Yeah, good question. Like if you exercise too much and you're a healthy a young healthy male You can actually decrease the testosterone level, right? Like andra's training can shut down your testosterone Production your reproductive system basically So that that trade-offs The kind of trade-offs we talked about with you know young females also applies to to males and in those kind of ways Where that threshold is I think is also highly individualized and Like overtraining syndrome is a very real thing And you know, even people who devote a lot of their life and energy to becoming better athletes Like there's a limit and I used to be a competitive cyclist and I I raised kind of semi professionally in my college days and Uh, and I knew that if I worked out if I you know was underrode And I used to do like intense and long distance workouts If I was like I logged all of my training, you know, how many hours kilometers all of this If I did more like 20 22 hours a week on the bike I would get like Achilles tendon. That was kind of my sweet spot Or my sensitive, you know weak spot or my knee So there was a limit, right? And and for me that limit was 20 22 hours And maybe that's why I never became a professional cyclist I I wanted to at some point that maybe uh after undergrad I'll be professional cyclist But you realize you need to spend a lot of hours on the bike to do this And my limit was that right? Uh, and I did some plyometrics and some other You know sprint Building exercises and I weighed like 10 15 more pounds and I do now I had I was investing more resources there Then when I started the phd, I was more inspired to you know, at some point It was like, okay, do I write this paper or do I go for a three hour bike ride and then spend like three hour Recovering, you know making a great amount of food and so the the trade-offs at some point I started to feel like I want to put my energy towards You know developing these ideas and so there was kind of a trade-off from athletic performance, you know And muscle building towards more intellectual activities and that sweet spot. I think is unique to each person And some people I think use running as a as a as a like a therapy Some people use eating some people use running some people use gambling, you know, whatever it is for you um, so I don't know that there is kind of a number of hours number of miles per week For sure not and whether you do something, you know, that inspires you or whether you do something and it's it's a it's a Fucking grind like I think that makes a difference for how much energy you have to do it and how much is good for you Uh, I know you spend a lot of time in the gym, uh, steven pressfield who you know, you're chatted to and this concept of resistance Right, like I think that there there's something there that you need to Give the body a certain amount of resistance And that's true physically but also true mentally Too much resistance crushes you right and then it's like too difficult and and it's demoralizing and de-energizing But not enough resistance is is not inspiring like and then then being bored like being imprisoned That might be why you know being in prison is so Such a it's a thing we do to people that have done really bad things because it is it really crushes a human spirit When you have nothing to do Having something to do is a bit is kind of exerting resistance to the human mind. So having to bumping your mind against something And that's something academics. I think really typically enjoy having a problem like being curious about something Yeah resistance through the lens of what we're talking about today is very interesting. I think it's uh worth underscoring it again Because we've established you've established. Let's be fair here. Uh, you've established that it's not just about Uh mitochondria making ATP and energy that are actually controlling energy flow transforming it All of the morse code rate and and content and then And so there's this allocation piece But then there's also this idea that in order to transform energy it has to meet meet resistance You know that that and that's where the transformation occurs and so perhaps the the whole concept of getting More vital getting better learning etc. It's about that feeling of friction. Yes, uh, when we when I've done episodes about neuroplasticity I've tried to really get into people's minds like The moment you feel agitation that that means the opportunity for plasticity is turning on Your brain doesn't change if it if it's in a state like any other state This is unfortunately why traumatic experiences are so good at rewiring the brain because your brain goes I'm not used to this much Adrenaline and norepinephrine something whatever's happening now is really important and it actually grabs too much and that's PTSD It grabs random events. It's it's a whole thing But for healthy learning Adaptive learning you have to have the resistance if you can do the thing your brain won't change Exactly if you can do the thing your body won't change and I try and explain this in the context of Cognitive stuff that agitation and frustration like you had to Seek that out. You don't want to overdo it. But I think if I wish they had told me that when I was in school I know right. I mean I was a pretty avid learner, but it's like you just want to tell people the moment you're frustrated Awesome like your circuits are primed to change. Yeah. Yeah. Anyway, I get very impassioned about this. So Because it's how we get better Yeah, and I think most people feel that and they think oh they're doing something wrong But actually the error signal that more and tell your brain you have to change Yeah, it's just it's just that the change takes time and it takes time and it takes energy Like the reason change is difficult transitions any kind of you know moving house is one of the most stressful things, you know that Divorced like you know getting divorced or your relationship changing relationships Any kind of transition by definition a transition requires change which requires energy And I suspect the reason why Life transitions are difficult is because they cost energy and we have a finite amount of it so resistance The energy resistance principle is something that we've developed recently with neurosis That encapsulates this it says like Life is resistance. You cannot have life if there's no resistance. There's no transformation Better could ever yes, exactly or you're like a beaming, you know Light ray in outer space that just goes on it just goes on goes on never transform You know there's a potential for change, but it's there's no transformation It's never going to change until it hits resistance a green leaf on earth for example. I love it It's such an important concept and just do it for I think you think about bodybuilding and you know Working out how the body gets stronger the way the body gets stronger is by facing resistance, right? If your muscles get accustomed to a certain weight if you want to grow and strength or in mass you need to go Heavier right and so it's increasing resistance same thing if you send an astronaut in outer space Their body gets like so weak their bones like demineralize and their muscles atrophy and you know their hearts weaken And then they come back on to on to earth And then they struggle and that's because when you go out in outer space, there's no resistance Right the gravity is you don't feel gravity because you're constantly falling right in orbit and then there's nothing Resisting the structure of your body. They age very fast. Yeah, exactly. The astronauts don't fare well. No now they have ways to compensate for this I'd like to take a brief break and acknowledge one of our sponsors waking up Waking up as a meditation app that offers hundreds of guided meditation programs Mindfulness trainings yoga need your sessions and more I started practicing meditation when I was about 15 years old and it made a profound impact on my life And by now there are thousands of quality peer reviewed studies that emphasize how useful mindfulness meditation can be For improving our focus managing stress and anxiety improving our mood and much more in recent years I started using the waking up app for my meditations because I find it to be a terrific resource for allowing me to really be consistent with My meditation practice many people start a meditation practice and experience some benefits But many people also have challenges keeping up with that practice What I and so many other people love about the waking up app is that it has a lot of different meditations to choose from And those meditations are of different durations So it makes it very easy to keep up with your meditation practice both from the perspective of novelty You never get tired of those meditations There's always something new to explore and to learn about yourself and about the effectiveness of meditation And you can always fit meditation into your schedule even if you only have two or three minutes per day In which to meditate I also really like doing yoga nidra or what is sometimes called non-sleep deep rest for about 10 or 20 minutes Because it is a great way to restore mental and physical vigor Without the tiredness that some people experience when they wake up from a conventional nap If you'd like to try the waking up app, please go to wakingup.com slash huberman where you can access a free 30 day trial Again, that's wakingup.com slash huberman to access a free 30 day trial I'm curious what your thoughts are about the fast emerging space of supplements and peptides that people are taking to ostensibly improve their mitochondrial function health output, etc The ones that come to mind are the following just to constrain it a bit because it's a huge space Coenzyme q10 A number of people including me take This isn't a plug for it. It's just I take it. I was told that can help my mitochondria Um, I don't take methylene blue. I'll mention why in a moment Uh, there are some peptides like ss 31 is very becoming very popular now cocktails of nad ss 31 Things like this people are oh, yeah people are injecting this stuff like crazy. Oh, yeah. Is s 31 I guarantee you within a radius of one one mile. There are a lot of ss 31 injected. We're in los angeles. So, oh, yeah ss 31 Um In cocktail with nad it's very common. There's uh, there are a couple others Slu slu. There's another one. All of this is um mot c A lot of people are injecting these peptides in effort to improve their mitochondrial function. We'd love your thoughts on this Don't worry. You're protected no matter what direction you answer Yeah, the term mitochondrial function mitochondrial dysfunction, you know I think are misnomers because mitochondria have many functions and um, so I think that the nomenclature That's more of a maybe a researcher kind of niche kind of thing But I think it's misleading to talk of mitochondrial dysfunction because mitochondria transform energy and make ATP But they make hormones and they make signals and but to your point about supplements You know, I was a student when ss 31 was discovered and I remember the the person we discovered hazel seto We discovered ss 31. She was presenting at meetings and and so I've seen the now it was commercialized you know, it's stealth peptide and then it went on the publicly traded so It's not lived up to its expectation. It was supposed to be a treatment for mitochondrial disease and mostly the trials have been negative um You know those things we're trying to tweak the system. I think what we're trying to do with supplements is to Uh optimize tweak the circuitry. You know the the metabolic circuitry that we have for flowing electrons to oxygen in an ideal world and electrons flow from food to oxygen Like two poles of a battery like a simple circuit with Like just the right amount of resistance Right too much resistance and then it feels terrible It feels like if you hold your breath and you're you feel like you're gonna die That's too much resistance not enough resistance feels like, you know, you're unhinged and uh, probably we think that's what mania is Right where you feel like there's so much energy that you it's you can't contain it and then you can't sleep and then you can't You know your life kind of falls adhg is another good example That that might be so maybe those kind of conditions disorders of of the mind we think are disorders of energy resistance We don't have you know direct evidence for most of it But I think that's a fairly well supported idea and supplements in cases when your circuitry is you know impaired Uh, like if you're deficient in in coenzyme q10 if you take it you're gonna feel it And if you're deficient in something like vitamin b12 there are many parts of mitochondria that require B vitamins to to flow electrons towards oxygen. So vitamin b deficiency different vitamin b including an ad right is Can really be terrible and people have chronic fatigue like syndromes from vitamin b12 deficiency for example so in cases of Where there's a deficiency or you think there might be a deficiency Maybe supplements can can help, you know palliate those my sense is You know, we've evolved over very long periods of time and we're really well optimized And the body and the mind are as two expressions of this energy flow kind of can work harmoniously together if we bring awareness to it And if we keep energy flowing through exercise through not eating too much and uh, you know being hungry once in a while I think there's ways to optimize the system and there's a lot of people who live long Healthy fulfilling lives and they get sick once in a while, but they recover without supplements and and without uh You know medical intervention, so I think there's a path to get there and so I think there's there's a place for supplements, but I've never taken a supplement and Can you have plenty of energy? I cultivate my energy in different ways and and I feel like it's It's a better investment of my energy and and my research group. We haven't studied, you know drugs or and We've been solicited to you, you know help pharmaceutical companies or other you know supplement type To test the effects of supplements in mitochondria if we go on that route then I think there's it's one approach that You know might lead useful results at some point but I feel like my energy my contribution as a as a scientist is better position and understanding the energetic basis of mind subjective experiences body and Developing a more holistic, you know system for for what we are, you know energetically and what we can do to support that Well, you're doing awesome work. So stay on the track. You're on. I just wanted your thoughts there um, and I should just say for for sake of being responsible, um Folks don't inject peptides that are for quote-unquote research purposes only people are getting them on the gray market I mentioned methylene blue, so I should just close the hatch on that one that I've avoided it for two reasons one I saw the images of blue brains from people who had recently taken it doesn't mean their brain stayed blue because they had taken it recently but there are some data that Point to the fact that methylene blue can Intercalate into dna and possibly cause some mutations there that worries me And there are some data as well and um chris master john talked about this recently That if people are mitochondrial Damaged efficient dealing with carbon monoxide poisoning other metabolic issues that perhaps methylene blue because it can reroute some of the uh, the Pathways for these electrons can be helpful But if people are generally healthy that it can cause more problems than it solves and that was enough for me to just say I'm going to just stay away from this stuff. Also. I don't want to have a blue tongue like a monitor lizard Anyway, that's not a serious thing But it just seems a little too it seems a little shaky for me and I do worry about people just taking it so um, and I'm very happy that your laboratory is focusing on the molecular aspects, but also You said the experiential aspects meditation meaning Purpose and this notion of flow is something that I want to just ask you about When you see things like tai chi if you're new york city You see people early in the morning if you get up you see them doing tai chi or years ago. I saw an interview with iggy pop Yeah, you know as a You know musician from the ash like the 70s and he's like in tremendously good shape now And has always been and they asked him like what's your secret? They always ask these kind of like what do you eat kind of things? And he was like it's all in the qigong breathing and it was I chuckled because tai chi qigong breathing I personally believe that whether or not it's running tai chi qigong breathing or lifting weights that the activity itself has certain benefits related to respiration blood flow muscle stress etc in recovery, but that The additional layer of benefit comes from the the understanding over time Yoga as well the understanding over time of how to direct energy in your body and mind To be able to force yourself to get through some hard repetitions But then to rest completely in the rest period to dynamically move from one position to another Not just as a physical movement, but as an exercise in being able to anticipate. Okay. Here comes the painful part I'm gonna not brace myself too much. I'm gonna try and quote-unquote flow through it But I'm also gonna put some restraint and pull back and so it's I do think that for every physical and mental activity There's the learning and then there's the Meta learning that comes from just having done it over and over so you you have this expectation and understanding You're learning how to allocate energy and I just like your thoughts about this. So I don't think it's qigong per se Tai Chi per se yoga pilates per se lifting weights per se. I think those have each different benefits But what are your thoughts about learning to be a better? Oh gosh, this sounds super woo, but what the heck? energy channeler Two scientists talking about energy channel Well, this is not woo. I mean there the mitochondria flow energy You can say they're channel for energy flow from biochemistry to electricity to ATP to Metabolites to reactive oxygen species. All of these are different forms or you know modalities of energy Is there like a molecular reality to qigong or to qi or to, you know, prana or right like maybe And maybe and if we look at all of these practices, right and and and we ask what's the point of conciliance? Like what's true? Maybe they all have like a little piece of the truth Like molecular biology and you know molecular sciences also has a piece of the truth, but it's not the whole truth and my sense is What is true that kind of is a bigger container to uh contain Both our molecular, you know physical existence and our experiential existence right the emotions the the state of consciousness states of mind that we know are real Uh crazy states of consciousness that we can experience with psychedelics for example What can Encapsulate right all of this. What's the bigger truth? And I think that bigger truth is that we are energy And we flow through this channel This body right we have mouth we have nose, you know lungs heart all of this you can Or the or anatomy human anatomy you can understand as an energy delivery and an energy flow system like a flow cell Right like a microchip and then there are gates that close and open and then you can process information Uh instead of electricity flowing through we flow food and then oxygen is at the other end pulling on electrons So maybe all those practices Have something to do with you know the movement of energy which ultimately is electrons flowing through your metabolism through your mitochondria But then there's an experiential dimension to that which is just as real We don't have scientific tools to measure this we can't you know image this with an MRI maybe not yet but I suspect there's a truth there and Maybe one piece of of that truth and that's you know the way you describe tai chi and the way you know we do Exercise like you you exercise you push hard and then you need to rest hard If you don't rest hard you're gonna ensure yourself and you're not gonna get as strong you're not gonna You know grow or you don't evolve Um mentally we need resistance And there's like so I think about energy resistance Brings us to think you know there's a philosophy of education that could be built around this You need to you know the the art of education is finding the right amount of resistance to expose a child to Right if there is a problem if the problem is too hard or you're too severe You're gonna crush them right you kill their their their spirit But if you don't apply any resistance, there's no rules then the energy is like this and then they'll never learn There needs to be like just a sweet spot Right, that's what great masters great mentors are able to do I think I started to see my role as a mentor for people in the lab You know like this a little bit I see them as energetic processes You know they're transforming energy. They need the right amount of resistance and you know not too much And it brings me more compassion maybe for them as as energetic movements And then I realize I'm more sensitive to the effect I have You know on them But all of this movement and the tai chi the exercise you know lifting and resting Is analogous to what the heart does the way that the the heart works is by contracting Cystalline right and then by relaxing And then contracting and relaxing the same thing for like the way neurons work boom action potential refractory phase You need to add that period of science right boom action potential and refractory Same thing with sleep wake cycles. You need to get awake your body temperature rises cortisol spikes up You're you know, you're aware of the world you're exposed to stressors If there's not enough stressors slash challenges slash meaningful things in your life you get bored and you want to die So you need that but then you need to kind of let go and and sleep right so sleep wake cycle same thing and maybe all of this as evolved from You know or existence on this planet like the sun rises Things get warm right and there's energy flowing around and then the sun sets the same movement as sunrise sunset You know day night is contraction You know resting yoga the the whole you know practice of yoga is based around this like you strain your muscles a great port Crazy positions, you know immense resistance on your muscles and then for what for shavasana And the whole point of yoga is shavasana So you you're ready the body by you know bringing so much resistance into it so that you can finally relax Uh, and and then the art of training maybe is not about the doing Right, but it's about the being And maybe that's a broader kind of philosophy of life, but the the art of being Which uh, because if if we do too much doing I think you know many professionals know this if you're always into doing doing doing and you're never kind of Uh sitting back and and resting and just being and being really means just flowing to use you know verbs Being is just having your energy flow and it's doing its thing and it's healing. You know, it's healing the body Um and consolidating memories and yet everything all the beautiful things that happen, you know During sleep and as opposed to transforming it into something in the outside world like a paper or investing or and it's the balance I clearly what I'm hearing and I don't want to speak for you, but what I'm hearing is that so much of health mental health and physical health and life really is about states of mind and body and Mastering the transitions into and through and out of those states But in a controlled way learning to direct those so that we're not at the whim of I mean This is the challenge that we get pulled into the drama or the numbing out of some online activity or the uh You know that the The energy of something going on over there that really pulls us You know and so I think we have to have that self-awareness But I love the idea that resistance itself is the thing to seek Not as a permanent state, but as a temporary state that you can then move through so and and I think if If clearly people learned a ton today, but if nothing else that they now understand the biophysical principle that it's through that resistance that you direct and create energy for something else transform you transform. Yes, exactly. Thank you Good managers notice like if you want to have Fulfilled employees right and a team that really derives joy and purpose like the people need to grow and learn um and And the way that happens is by creating the right amount of resistance and uh, uh, Steven Pressfield Said this the first time I heard of him. He was on the jarogan podcast talking about his book and Resistance and he talks about it in slightly different ways, but I think his resistance philosophy Boils down to energy And he talked about how when you feel afraid of something right like as an artist I think he speaks, you know as an artist and for artist like you You you you feel into like this problem or this challenge or you know this new project you're like, oh, I don't know like this is scary Shit. Well, I think his his advice was when you feel fear This is the signal that there's something there for you right that this can help you grow um and and I resonate with this and you know, I I make a lot of you know, my decisions I can think rationally and think logically about steps in a Biochemical pathway and about like logically like in five years and ten years like doing strategic planning but I have an increasing Sense that When you make decisions with your heart And basically this is by listening to your energetic state You feel you see something you see someone you're like, oh, like I like this or that this is a little scary, right? I started to ask my wife, you know, and she's really good at this. How do you feel? I think I used to ask my partner What are you thinking? And if you ask someone, what are you thinking like right away? You go into this like cognitive level, which is really devoid of like the beautiful um movement of energy if you ask someone How are you feeling? And then if if that person if you can you help you you make you create a space for that person to really Answer from that place then you actually get to you know Tune in to their energetic state and then you can be I think much better partner if you see a relationship as an energetic Exchange right and then And then I can be a better I can be in a better state if I know that oh, she's not feeling great and and then I think we've I think the more you cultivate this kind of energetic awareness. I agree Awareness personal awareness and I would say energetic awareness Feeling into your mitochondria. Maybe that's what it boils down to. I think it's our greatest superpower as human beings and and that's not a new concept It's I think the foundation for you know a lot of spiritual traditions like cultivating awareness Of self and then you realize at some point there's no self I'm just like movement of energy and then you movement of energy And then we're all kind of arising emerging from you know an underlying current of consciousness and you know their ideas about this I'm not sure how it all you know fully gels together, but Awareness also as a scientist if you move through science without self awareness Then your biases end up ruling the kind of projects you take on and end up ruling the kind of grants you apply to and end up ruling the kind of science you you produce and you generate and and So without self-awareness, I think we're not always doing your fulfilling or potential and Fulfilling or collective potential right as as as humanity like we can If we can be the best person that we can be then we can help other beings You know being their best self we can be present and when you're present to someone is basically saying I see you energetic process and I'm opening to you. You know, how are you feeling? You know, that's why I think those kind of conversations and connecting deeply with another human being is so rewarding and and that's That's true. I think across the board we're social creatures and what this means is we love connecting with other people And and I suspect that's because it helps us flow right? It helps us, you know our energy flow and then we we love projects that are stimulating You know inspiring and what those words mean stimulating inspiring. They're all like energetic terms So the things that helps us flow being like cognitive or spiritual or you know intellectual, you know Social all of those I think probably boiled down to Is is this thing helping energy flow through our mitochondria more easily or is it bringing me of resistance? Or is this thing bringing me resistance that I feel I have the capacity the inner You know potential to push through and then when I let go then I become stronger right and I grow as a person and and I learned I love it. It's a mitochondrial Uh or any energy flow centric view of of everything and I think it is the basis of life I know you're working on a book now Um, uh, it sounds like there's also another book uh to follow that one the the mitochondrial marriage At some point I'm only half kidding What you described is is really beautiful and it uh, and it captures so much of what people are seeking and I think what people understand intuitively about the Things that make them feel good versus the things that make them feel bad And the we have to pin above that that resistance is critical to growth So it's not just about things that don't take effort versus things that take effort So it's it's not it's not as simple as that. It's uh, it's not infinitely complicated, but it's not as simple as that speaking of of solutions Before I came in here to talk with you. Uh, I solicited the the internet for some questions. We sometimes do a a Uh, not rapid fire, but brief answer q and a so if I may I'm going to go fetch my phone um And gather a couple of questions to ask for some short answers first question is Why is it that over consuming calories? Causes disruption to the mitochondrial pathways Yep, I think it's because it increases energy resistance It's like, uh, a simple electrical circuit, maybe a computer and then you're cranking up the voltage Right, so you like pushing when you eat too much you're putting too much Food too much energy into the system and then the system gets overwhelmed And then that increases blood glucose or you know blood lipids and so the effect this has we understand it It pushes electrons onto your poor mitochondria mitochondria evolved to be super sensitive and then when there's like a bit not enough energy they change your behavior If there's too much energy they change your behaviors are chronically too much energy pushing on them If you do the we have a little equation that helps us think energetically about this called the energy resistance principle erp And this says if you raise the concentration of glucose you raise the energy potential like the voltage equivalent And then that increases energy resistance if you're not flowing that energy If you're not moving, you know being active stimulated by something you just put too much food in the system It increases the the resistance to energy flow and then you start to have more dissipative losses like too much reactive oxygen species and too much You know the damage molecular damage can happen. Uh, that's probably why overeating and why diabetes and why You know metabolic diseases increases the rate of aging and increases the rate of all sorts of these different diseases And they get all converges on energy resistance Someone asked has there been any progress made on tissue or organ specific mitochondrial? optimization and i'll add to that End or measurement. Mm-hmm. So the measurement piece we're working on this the anamonzo inner group Who's moving to germany now is developing a mitotyping platform And if you want to explore kind of the if you're a scientist or you or not Then you want to explore the the molecular differences between mitochondria and different organs of the body you can go to mitotype explorer.org Uh, and then explore the different mitochondria and different organs tissue organ specific mitochondrial optimization I think Mostly is going to be driven by the the organ or tissue specific use and and you know flow of energy and that tissue like we were talking about earlier if you Train on something you train, you know, i'm playing the violin you're gonna parts of your brain are going to be you know more activated specific circuits are going to be Activated together they're going to you know wire Together and and then you know make more mitochondria most likely and and you know probably become more efficient as well So there's rewiring at that level So I think it's mitochondria follow or there to to serve the flow of energy So if you flow more energy in your legs, you're going to make more mitochondria to kind of increase the number of flow channels mitochondria has little you know Channels to flow energy towards oxygen so Yeah, I don't know that we have ways yet. Maybe with uh, you know light therapy Photobiomodulation or maybe electromagnetic field at some point We need to be developing as you know healing science Unfold and we understand ourselves energetically Uh, I think we need energy base or energy informed approaches to Help organisms heal and and probably those are going to target mitochondria Yeah, using light or other tools to direct healing of internal specific internal organs That's going to require something A device of some sort as opposed to using one area of the body or one component of the brain is what i'm hearing Most likely although there's some like crazy things that monks can do apparently like increasing the blood flow in one hand, but not the other there's even data showing that Advanced meditators can increase blood flow in like one part of the brain and so There there might be unsuspected ways of tapping into You know using the mind basically to direct energy in different ways. I've started to See the mind as you know a master regulator controller Of energy like the mind can literally depolarize your muscles, right and then cause you to run Right that it starts up here with the the the inspiration or the motivation to Contract your muscles and or to run or to do any behavior This is like the mind controlling the energy flow in your muscles and then making more mitochondria as a result What are the best or most sensitive tests for mitochondrial health? If any exist and I will say a number of questions and there were many many questions centered around this idea Of you know, how can I measure mitochondrial health as a patient or as of you know with my Physician are there any companies that make good mitochondrial health tests? There are diagnostic tests that you know clinics offer somewhere and those are good to diagnose mitochondrial diseases um there's a few you know companies that have popped up because This is a future like thinking ourselves thinking about ourselves energetically realizing we are energy If that's true, which I think it is then what do you do about this? And uh, I suspect we're working on developing an institute that will Really bring together the signs of energy mitochondrial biology and psychobiology with the human experience That really is what moves us into into into action and Determines whether you know our lives is as we're living those things have been brought together And and we haven't also explored scientifically the healing process So we're developing an institute that will you know work do the research to develop those technologies and then we'll do the work as well to bring those into um Into technologies that can reach people and you know people can have in their homes and maybe as a wearable or Right as a as a kit that you get at home to really help you tune into your your energy and know what works for you which diet which uh supplement or which you know There might be You know, it might be that this person in your life when you're with them It's energetically it really does well for you and maybe that means it's a good person for you And there might be other people that you know really suck your energy um, so we're working on on initiatives and uh New methods to tune into mitochondrial health. I don't know now of things that I would use to tap into the the health of our Mitochondriot. I can attest to both the pro mitochondrial health and anti mitochondrial health of certain relationships What are some Small daily tweaks that can help increase and people said energy But let's just use that as a proxy for energy flow like if you could give just one Two or three recommendations. There are a lot of busy people in this question list. They're saying I've got kids. I've got a busy job So One two or three things that are straightforward outside the typical You know exercise get your sleep, etc. Is there what what are some tweaks? dare I say hacks I think trying not to eat in the morning like skipping breakfast seems like it does a lot of well for a lot of people And I've heard for a long time breakfast is the most important, you know, meal of the day that my dad used to say that He still believes that and I think it's hurting him his health and is like now in the 60s So I think like trying to be hungry once in a while is probably a good thing And then when you feel that hunger and then you you're like reflexively reaching for food Like think what you're I think you're probably doing something good for your mitochondria Your mitochondria when you're hungry or when a cell, you know what we know that the science is If a cell is hungry in the dish the mitochondria start to fuse and there's more kind of the social connection Between your mitochondria So maybe it happens inside the body and then you get rid of the bad mitochondria You make more new ones that work better more and more efficient So being hungry once in a while is probably a good thing and then being out of breath You mentioned one of your friend. I think who says like I just need to be out of breath for an hour Finding ways to be out of breath that can be like a run can be being in a gym You know, whatever makes your breathe harder You breathe harder because your mitochondria are calling for oxygen. It's it's that simple So if you feel like you need to breathe harder, it means your mitochondria are flowing more energy and it's probably good for you Great. Yeah, I need to say something about meditation. I think somehow meditation does something to our energy That is valuable and just yesterday there was a piece published in nature reviews cardiology About transcendental meditation. I think that shows that the world is changing, you know, a clinical medical journal like nature reviews cardiology saying maybe there's something about like Calming down the body, right? And not only is this like calming down the mind. Sure Like maybe it improves well being this could actually be a treatment to help the heart recover Right and to help treat a very serious Um, you know life-threatening disease cardiovascular disease. So that's I suspect there's something about meditation I have a 10 minute every morning. I sit down and says I'm religious about this I wake up first thing I do is sit down for 10 minutes with sam harris is waking up up and I just It just helps me connect ground, you know connect with my energy and then I think There for the rest of the day, I'm a little more in tune and I probably can make better decisions and I'm more grounded Um, you know mentally but probably also physically awesome There's a lot of discussion about peptides Mott Mott C humanin ss 31 also called a lamma Pre-tide. I didn't know that. Yeah, uh, ghku copper and various bpc 157 tb 500 analogs I tell you this stuff's getting popular People are curious Uh, let me ask you this. I'll jump in on their question because we talked about some of this earlier Would you inject any of these things? I wouldn't Would you let your sibling mom or dad inject these things? No, there were many questions centered around the fact that Fertility doctors obgyns are recommending various things to improve mitochondrial health For sake of fertility and egg quality This makes sense because the mitochondrial genes are involved in this Bindle and the formation of the embryo, etc. And there are the questions were specifically about Uh, the recommendations of ubiquinol and coq 10 Urolithin a these are very prominent in the in the health space especially in the fertility health space right now Is there any real evidence that these compounds can improve mitochondrial health and and therefore egg quality? There's some good data on urolithin a That improves quality and cultured cells and then in animals um So it's possible and I think I saw recently some very compelling data on sperm mitochondrial DNA content mitochondrial DNA content like per sperm Um Link to infertility. Uh, so I suspect that this massive crash, which is really Worrying infertility. Um, we're well below replacement right now. We're having very few babies as a as a society It could be that part of the the issue behind this is mitochondria aren't You know as as optimal as they should be and or the or energy is not flowing as as freely as it should be So I don't know about the Whether those treatments could solve the issue my sense is the issue behind infertility is is not Doesn't arise from some molecular deficiency in our mitochondria. It arises from some higher level process That ends up missing upper energy last question Feel free to pass on this one. There were a number of people who asked Whether there is any evidence animal studies in vitro or even in humans that electromagnetic fields can disrupt mitochondrial flow This is I realized somewhat of a barbed wire topic because it immediately gets us to the place where people think oh, they're You know worried about you know 5g and bluetooth and things like that, but I don't know I did an episode on fertility where I reviewed a meta analysis of Data showing that indeed sperm motility can be impacted But what are the data on emfs or other electrical? Signals or other energy fields that um could potentially impact brain sperm eggs If there's you know something in Most cells that could respond to electromagnetic fields. I think it would be mitochondria if you reason about this from first principles In the mitochondria, there's a bunch of iron, you know iron software clusters, which uh Some of them at least are paramagnetic meaning they interact with magnetic fields So I think in terms of biological plausibility I think there's basis to believe that mitochondria could be sensitive and you know respond and be functionally impacted by some For you know magnetic fields So that's for biological plausibility data I know some data where people have measured mitochondria respiration right which is flowing electrons to oxygen and uc oxygen disappearing So you can measure this very well in the lab And then you can measure this in the absence of any magnetic field and then with a bit of a field a stronger field a stronger field Stronger field and it seems like there's there's there's an effect on this one function of mitochondria, which is Uh respiration so there seems to be data that says this this could happen Uh what we're talking about in terms of magnetic field there is not 5g and it's not you know some Uh like wi-fi widely used magnetic or you know fields are Uh electromagnetic radiation they're pretty specific and you know the earth's magnetic field Which is in like very low level seems to perhaps have an effect also on on mitochondria And uh, there are biophysicists like my wife Nerocia Mjurgen who has done experiments with pattern magnetic fields Which is uh different than just you apply a static magnetic field like with the magnet right or a field that doesn't change over time It's like a sine wave. There's no information there, but you can pattern a magnetic field to have Information to have content like morse code, you know back to the morse code analogy So you can deliver information through that and it seems We have preliminary data that that shows the mitochondria might be changing in response to You know this basically you're beaming energy at a certain a certain pattern instead of with molecules like glucose and pyruvate and lipids and stuff and you're or light right now you're beaming energy is in another modality as electromagnetic waves and And their proteins clearly that an iron sulfur clusters that can be sensitive to that So I think there's some biological plausibility. There's evidence that this might happen and affect mitochondrial respiration and and There's I think another layer of sophistication that tells us this Potentially could be harnessed eventually to help kind of rewrite some energetic states in the body Maybe we can use those at some point to promote the healing process Love it. We'll see We will see Dr. Martin Picard, thank you so much. You gave us a master class in mitochondria mitochondrial function you clarified a lot of What is clearly confusion for people out there including many biologists mind you about how mitochondrial work and the spectacular things that they do and the way you frame This whole notion of energy flow and I guess we should credit your wife here for Energy is the potential for change. Right and the behaviors the mindsets The small moments where you can give yourself relief like an exhale and just take the tension off the body those are surely creating it energetic savings that you can allocate to other things and to just think about life as a as a Game of sorts of of controlling your energy and it gets us to sleep and all the things that we love talking about on this podcast And the way you framed it is truly novel and it's just spectacular. Also You're reversing graying of hair People you're giving people agency over that and I just want to reemphasize that how Incredible it is that you're approaching things at this very high level of subjective experience It's very real level that people live in all the time And yet you're able to bridge across all these levels of analysis down to the subcellular and biophysical mechanisms It's really spectacular You're truly an end of one as as we say and i'm very excited for what you're putting together in terms of this scientific institute to solve healing Your book we'll talk again later at some point about your book and I should probably also sit down and have a conversation with your wife because she's got some spectacular results in this realm too and Uh Just thank you. Thank you. Thank you for the education and the actionable items that you're providing. Thanks for coming out all this way Very grateful to you. Thank you. Thank you, Andrew Thank you for joining me for today's discussion with dr. Martin Picard to learn more about his work Please see the links in the show note captions if you're learning from and or enjoying this podcast Please subscribe to our youtube channel. That's a terrific zero cost way to support us in addition Please follow the podcast by clicking the follow button on both spotify and apple and on both spotify and apple You can leave us up to a five star review and you can now leave us comments at both spotify and apple Please also check out the sponsors mentioned at the beginning and throughout today's episode That's the best way to support this podcast If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman lab podcast, please put those in the comment section on youtube I do read all the comments for those of you that haven't heard. I have a new book coming out. 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