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

What's the deal? Can people reverse the graying of their hair by reducing their stress? Can people accelerate the

stress? Can people accelerate the graying of their hair by stressing more?

Likely both are true. Yes.

>> Okay. And I think what we discovered is that hair graying, at least temporarily, is reversible. This was surprising

is reversible. This was surprising because it goes against this notion that aging is a linear, you know, uh, process that just happens over time no matter what you do. And here we should know

actually a a hallmark of aging which is you know depigmentation losing color and your beard and your hair um is something that happens to almost everyone but at different you know stages of life and

and so on and then on the same person and the reason we got into this was that this felt like the perfect experiment.

Every hair has the same genome. They're

all genetically identical twins, right?

And they're all exposed to the same exercise regime, the same food, the same stress levels. Uh but yet some hairs go

stress levels. Uh but yet some hairs go gray when you're like late 30s and then some hairs go gray when you're like in your 80s. What the hell's happening? If

your 80s. What the hell's happening? If

we could figure this out, maybe we can understand why different people age at different rates.

>> Mhm.

>> Uh because it's very clear that there's no more than 10% of how long you live that genetically driven. Like the best studies put this at around 7%. 7% of of

longevity is genetically inherited maybe and then about 90% is not. Welcome to

the Huberman Lab podcast where we discuss science and science-based tools [music] for everyday life.

I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at Stanford School of Medicine. My guest

today is Dr. Martin Peard. Dr. Martin

Peard is a professor of behavioral medicine at Columbia University. He is

also a leading expert on how your daily behaviors and your mode of thinking, meaning your psychology, change energy production in your cells and can accelerate or reverse biological aging.

Most people have heard of mitochondria as the energy producing organels within their cells. And of course, that's

their cells. And of course, that's linked to what we call metabolism and metabolic health. And of course, most

metabolic health. And of course, most people understand that eating properly, exercising, and sleep are critical for metabolic health. But it turns out

metabolic health. But it turns out that's only part of the story. As Dr.

Bicard explains, "Mychondria don't just make energy. They act as sort of

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

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

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

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

reversible. By the end of today's episode, you will not only have had a master class in mitochondria, he explains mitochondria with immense clarity so that you really will understand how these incredible organels

work to produce energy and as these sort of antennas to direct that energy from outside you and by the things you do.

And by the end of today's episode, you'll also have a lot of actionable items that you can apply toward your health and to offset aging. Before we

begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is

however part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include

sponsors. And now for my discussion with

sponsors. And now for my discussion with Dr. Martin Peard. Dr. Martin Peard, welcome.

>> Thank you. Your work is so relevant nowadays. I suppose it was relevant

nowadays. I suppose it was relevant always, but these days we hear so much about mitochondria. Most people have

about mitochondria. Most people have perhaps heard of mitochondria, they think the powerhouse of the cell, but you're going to tell us that it's a lot more than that. And I should say right

off the bat that if people think that perhaps a discussion about these little organels we call mitochondria is not for them, keep in mind Martin's laboratory was the one that discovered that you can

indeed reverse the graying of your hair.

Uh that graying of hair is not a prerequisite uh of aging. There's some

other ways that hair grays. So we'll get to that later. Super interesting work. I

have a million questions for you. Let's

start off with the most important and most basic question which is what is this thing that we call energy? There's

electrical energy. We know the sun gives us energy etc. But when we're talking about the energy of life >> physical and mental vigor, the feeling that we want to do something as opposed

to have to force ourselves to do it.

What is this at the organism and cellular level? I mean even physicists

cellular level? I mean even physicists don't agree on what energy is and there's been debates you know Richard Fineman who was like this amazing science communicator physicist said like

we don't even know what energy is and what's the best way to define it because there are all of these forms thermal energy heat right energy electromagnetic

uh kinetic energy movement speed right uh potential energy so uh energy kind of manifests in all of these different ways so in in a nutshell I think the best definition I've I've heard heard uh from

my wife Nosha is uh who's a biohysicist energy is the potential for change >> right so and that applies to any kind of form any form of energy you can think

about it's the potential for change for changing something in the system and that's uh I think an accurate description of you know thermal energy

if something is frozen solid there's no you know potential for for moving something we need to be at 37 7 Celsius, right? The human body it gives us the

right? The human body it gives us the potential to move and muscles to contract and you know our biology to to to function. So this is just one example

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

energy. You need to be a little warm to be alive.

>> Um uh so the potential for change and then it manifests in all these beautiful ways. Uh and it's something that flows.

ways. Uh and it's something that flows.

You know when a key property of of energy is something that has the ability to flow and to transform. So you can never create nor destroy energy, right?

That's like a fundamental law of thermodynamics. But energy always

thermodynamics. But energy always transforms. So you can transform heat, right, into motion, right? And like the the steam engine, for example, through pressure, another form of energy. Uh or

you can transform electricity into, you know, a picture on your screen. That's,

you know, what your computer does. uh

transforms your raw energy electricity into you know a picture a sound or um so that's what happens all around us. It's

all you know energy moving transforming energy from the sun this outer you know reactor in you know nuclear reactor in outer space beams energy at us and then what plants do is they take that energy

transform you know light into biochemistry and then you get energy which used to be immaterial that gets crystallized into biochemistry and then

we human beings animals eat that biochem cold energy and then the inner mitochondria that energy gets transformed Right? Again, the potential

transformed Right? Again, the potential for change and then the that biochemical energy gets transformed into an electrochemical gradient. Like you

electrochemical gradient. Like you charge your little batteries, your mitochondria and then that's another form of energy which again is a potential for change. And then you can make ATP with this. You can make reactive oxygen species, you can make

hormones, you can you know all of the beautiful things that mitochondria do.

So energy is that potential for change that has all of these different forms that continuously transforms. >> Amazing. Or you can use your brain to

>> Amazing. Or you can use your brain to create technologies that create other forms of energy or excuse me transform other forms of energy.

>> Exactly. uh and your question it was about you know the the human energy vitality like you know the the the energy to do something and that's I think another manifestation of energy as

energy flows through this thing that we call biology or you know the the human body uh it kind of moves us into into action right and uh we know from first

principles that the the the basis for human experiences you know the mind and our ability to be inspired to to feel you positive things or to feel negative

things depends on the flow of energy, right? That the difference between a

right? That the difference between a thinking, feeling, conscious person having experiences and uh being able to go to the gym and lift and like or and a

cadaavver is really it's not the size of the muscles, the number of cells, the nucleus, the genes, the mitochondria.

It's none of this. The difference

between a living person and a cadaavver is the flow of energy. When you die, all of the structure, you know, the physical stuff remains as is, but energy stops

flowing. If you stop breathing, if your

flowing. If you stop breathing, if your heart stops beating, energy flow stops and then energy transformation, therefore it can't happen. And then

that's what we call death and then the mind dies, right? Like you you don't have an experience anymore. And um so the flow of energy I think has to be the the the basis not only of life which we

know you know to be to be correct but also the basis of human experiences and what we experience as energy. We think

about energy. We we crave energy and we know and the way we talk about you know this person is really good energy or this thing you know really energize me or you know had this great idea your friend was telling you I had this great

idea I'm buzzing man like what's that buzzing thing it is a real experience and uh most people have you know had the the experience of feeling really excited

about something right a new idea a new person and then you know you have butterflies and you know their emotions going on in your body. I suspect

emotions the best kind of first principles definition of an emotion is energy and motion >> and uh we can talk more about like uh what we experience in terms of energy

but I think it's pretty clear we don't experience energy per se like you don't have a direct experience um an empirical uh you know access to

how much fat you have in your body like there are hormones that communicate and you know how much energy is in your liver and or how much you heat uh is is in you know something what you feel what

you experience is a change in energy when energy moves you feel that right and I suspect that's what emotions are there's like a movement of energy something shifts and then you experience

that a bit like uh uh like if you're in a car and your eyes are closed and you're going constant speed right kinetic energy you have no way of knowing from first experience if you're

going at 100 miles an hour 10 miles an hour or if you're standing still. These

are very different energy, energetic quantities, right? The kinetic energy.

quantities, right? The kinetic energy.

Uh what you do feel is acceleration and deceleration. You feel the delta in

deceleration. You feel the delta in energy, >> right? The change in energy,

>> right? The change in energy, acceleration, deceleration. Same with

acceleration, deceleration. Same with temperature. Like if you touch something

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

feel it. You don't feel, you know, room temperature, you know, or body temperature. What you feel if some you

temperature. What you feel if some you touch something that's cooler than your body, what you're feeling is not the temperature of what you're touching.

You're feeling your temperature leaving your body, right? It's the heat of your body leaving through conduction towards this. And then that's what you

this. And then that's what you experience. And if you touch something

experience. And if you touch something that's hot, you're not feeling in the energy of the thing, you're feeling the heat that's coming into your body. So

you feel that delta and that change. And

that's how human perception also uh works. like you we're able to see colors

works. like you we're able to see colors to see light. You've studied the the visual system a lot. You know,

fundamentally the ability of the eye of the retina to perceive, right? To to

sense light uh requires that you bring photons, right, that are beaming from whatever source, short, long wavelength.

Uh you need to bring them into stillness, right? You need to resist the

stillness, right? You need to resist the flow of of of photons. And then so you change the speed of the photon and it's that change in energy. you get kinetic energy, speed of light [laughter]

and then boom that when that that the the delta v the the change in in in speed uh happens this is when you can you can trigger you a calcium release

and then molecular series of events and action potential and so in order to see you need to resist the flow of photons right you need to uh resist you know

energy movement and then that triggers a transformation same for hearing right we here and I hear your voice uh because my eardrum resists the pressure waves that

you know you're producing. So your

energy is being channeled and projected through through the air as sound waves, another form of energy. And then I'm feeling you right through your energy

that's carried through the air. And then

because my eardrum resists the the pressure wave that you're producing and then it's that resistance right and that change that delta again in in speed by resisting your the sound waves coming

from you by resisting your energy now I can perceive them and then the little osticles in the ear that transmit what used to be pressure waves into now mechanical motion and then into like fluid into the inner ear and then the

cilia that move and then ions that come in then eventually they get transformed into electricity right so again it's one form of energy pressure waves turn into electricity and then the brain uses

electricity as a form of energy. There

can there are many right but that electricity is just so amendable to computation processing and integration.

So once you have this common energetic language for sight for hearing for you know uh touch and smell and and taste then you can integrate that we perceive

energy uh transformation and change in energy. We don't perceive energy, you

energy. We don't perceive energy, you know, per se.

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Your description uh brings to mind a number of things but uh years ago a colleague of mine who unfortunately now has passed um stopped me in the hallway at Stanford this was Ben Barers my

postto adviser later my colleague as a faculty member he said why do we have so much less energy as we get older and [laughter] I said well it's probably not a concern with you Ben I mean he was known for having

tremendous amounts of energy he probably only slept four or five hours a night but in any case I said I don't know and he goes well how come no 's working on that? Like, why are we working on all

that? Like, why are we working on all this other stupid stuff? And I won't tell you what he listed off cuz some of it was stuff in his laboratory. Um, and

I said, "Well, that stuff's interesting, too." He goes, "But nothing is more

too." He goes, "But nothing is more interesting than why we have less energy as we get older, except perhaps why it is that the brain can't change as readily >> and when we're young as opposed to

older." you said something very

older." you said something very important to uh underscore and that I'd like to get into a bit more which is you said you know or your partner said um uh

energy is the potential for change and you mentioned emotions they stir us right and that that feeling especially of positive anticipation is so much of what we live for in fact the

>> the signature feature of major depression is lack of >> of kind of any idea that there is a future worth living into >> apathy.

>> So apathy etc. Whereas vitality and excitement and everything good about life is about wanting to know what comes next. So if we take a um a biohysical to

next. So if we take a um a biohysical to cellular to psychological set of steps here we would say that somehow energy is

converted into uh this internal vibration which we call emotions that let us sense physically sense into a future

>> could be even a negative emotion but that but it still senses into a future and then you give this example very dramatic example but believe appropriate of a cadaavver where

all the material is is still there right after death before it degrades right but it can't move and therefore there is no future sense >> it's a very a very different way of of

thinking about death so >> let's talk about um psychological energy and physical energy that we call vitality um and if you would is a bit of

a challenge but could you perhaps use that as an opportunity to teach us about these incredible organels that we call mitochondria.

>> I use a slide uh often as an opening slide when I give presentations to academics or non-academics uh which is kind of a mitoric view of the world,

>> right? Like at some point we realized

>> right? Like at some point we realized that the the earth was not the the center of the world and then we switched over to a different form of a different you know model of the universe. So my

sense is we need to do something similar for uh in biio medicine. We still have I think in most people's mind especially the older generations a very gene

centric you know nucleioentric view of biology that the genes are there and then central dogma right the genes drive RNA drive protein and then drive phenotype uh and we know that that's not

the full picture and there's a lot of end phenotypes for example and genetically identical mice right there are mice that all have the same genome and some are like very anxious and some are super chill

it it can't be encoded in the gene somehow. We found recently that's

somehow. We found recently that's actually there differences in mitochondria and part of the reason why these animals behaviorally are different maybe half of what half of the varants half of like the the interindividual

differences what makes one mouse super chill and the other the brother the sister that is genetically identical uh very anxious has to do about with

energetics in in some way. Um so I use this slide to convey this mitoric uh perspective if you want to have a copy and you know show people um I'm happy to

share this and one way to understand this is energy comes into the organism as food we eat and we breathe to fuel our mitochondria right so the the reason

you breathe is to bring oxygen into the body most people know this and then once oxygen is in your lungs it goes into your blood and then it goes to the heart and then the heart kind of boom distributes this you know across a whole

organism. Uh and then when oxygen gets

organism. Uh and then when oxygen gets you know to your big toe or to your muscle or to your neuron and you know the your hippocampus or some brain region um what happens is the oxygen enters the cell and then once it's

inside the cell it looks for mitochondria looks I mean it's attracted by a concentration gradient. So that's

the mitochondria is where oxygen is consumed. uh and then when mitochondria

consumed. uh and then when mitochondria consume oxygen they basically create a downhill slope for oxygen to kind of be attracted to that. So you breathe to bring oxygen to your mitochondria and

you eat to bring electrons into your mitochondria. And uh what happens there

mitochondria. And uh what happens there is you know this beautiful sequence of of of a reactions where you have electrons from that were initially stuck

on food by the plant. You know taking solar energy to stick electrons onto carbon and then you make hydrocarbons and then that's you know glucose or starch or and then li oils lipids

everything that that's good for good fuel for mitochondria. those things, the food and the oxygen converge inside the mitochondria and then finally the uh the electrons that were you know ripped off

as CO2 is broken into oxygen and and uh or reunited in your mitochondria and so your mitochondria actually make water uh and and and then release CO2. So that's

the they close the life cycle that you know we have with photosynthesis.

photosynthesis makes oxygen and food and then our mitochondria brings those two things together and then they release water and CO2 exactly what plants need.

So it's this beautiful cycle. So when

mitochondria do this uh is basically uh feeding unpatterned energy into the system and it starts with with the mitochondria the same way that if you

feed electricity into a mo morse code right like t um you feed electricity it's unpatterned energy like food and biochemistry is to your body and then

you by pressing and releasing a little lever right with a specific pattern what you're doing is you're patterning electricity which means means nothing.

It's just, you know, raw current. And

then you pattern it in something that means something. Short beeps, long

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.

time, right? By patterning electricity.

So mitochondria, the way I see them is they're kind of an energy patterning system.

>> And we've called them the mitochondrial information processing system for that reason. Should we think of them like a

reason. Should we think of them like a little morse code um lever? I

>> I think it's a decent you know analogy for uh you know part of their behavior, part of what they do fundamentally. They

take raw energy and then they pattern that energy into molecules.

>> This perhaps is why I've heard you say that we should not just think about mitochondria as the powerhouse of the cell generating more ATP.

That is true, but it's also true that they're controlling the flow of energy in a very detailed way.

>> Correct. And they're controlling the flow of energy, but they're also controlling um the transformation of energy, right? The electricity, you

energy, right? The electricity, you know, can be converted, transformed into all sorts of different messages, signals, right, with your MOS Morris code depending on the needs, depending on, you know, the state, depending on

the person pressing, releasing the lever. Um, and sometimes the organism

lever. Um, and sometimes the organism needs a lot of ATP. If you're a mitochondrian and you live in the heart and your job is to make ATP, a lot of ATP and then there's side jobs. If

you're a mitochondrian in the liver, your job is very different and you're a very different kind of mitochondrian.

>> Well, let me ask you this. Uh, I think you just answered the question, but >> are there different types of mitochondria?

>> Yes.

How does a mitochondria in the liver versus in the brain versus in the heart know to take the energy that it's transforming >> and pattern its output so that heart

cells can do what heart cells need to do or liver or brain?

>> Uh this seems like a very important issue. Um

issue. Um >> is it possible even that the mitochondria and these different tissues are fundamentally different organels?

And we should probably define what an organel is for people.

>> Yes. Yeah. Organel is the the technical term uh for an organ of the cell. Uh and

the cell typically is represented as this you know skin and then inside the skin is the cytoplasm the big soup. And

then inside the soup the cytoplasm there's a bunch of little organs that allow the cell to do all sorts of uh things and perform its activities and replicate and so on. Mitochondria is one

of those organs. uh and their purpose is to uh process transform energy. Uh and

one of the ways in which they they transform energy is taking raw uh energy from biochemistry the the food you eat uh empowered by oxygen to you know flow

those electrons and then making building a a charge and then powering this beautiful rotor. Uh some people might

beautiful rotor. Uh some people might have seen this. It's kind of a a rotary, you know, uh engine kind of thing. a

turbine uh and then when the mito when mitochondria build their membrane potential to become charged they use that charge to power the rotation of this turbine and then as the turbine

turns it converts ADP into ATP so now you have conversion of biochemistry into electricity and electrochemical charge in the mitochondria back into biochemistry ATP what's um in the

backdrop of all this of course is that all of this self-organizes during development that yes the genes are the blueprint but This is all built up from scratch and probably a a a tangent for

another time. But

another time. But >> so how does a a heart cell know to produce >> a lot of ATP versus a liver cell? And of

course it's coordinated in time with sleep and circadian stuff, but how does it know or does it even know I'm a I'm a mitochondria inside a heart cell and the amount of energy I need to transform is X?

>> Yeah. How does a mitochondrian right singular is mitochondrian and multiple is mitochondria. Uh how does a

is mitochondria. Uh how does a mitochondrian and a hard cell know that it needs to be a cardiac mitochondrian right? Is that your question?

right? Is that your question?

>> Yeah. Is it is it genetically different than a mitochondrian from uh the liver?

>> No, they're genetically exactly the same. And uh and that's another uh kind

same. And uh and that's another uh kind of punch to the the gene-based, you know, model of biology. How could it be that every cell in your body is genetically identical? Uh and the

genetically identical? Uh and the mitochondria have their own genetic material.

You we all have our mom's mitochondria, which is really beautiful. Again,

>> 100% of our mitochondrial genome is from mom. Is that true?

mom. Is that true?

>> Correct.

>> Okay.

>> And there were a few papers a few years ago that said, "Oh, no, look here.

There's this like re this one case, [laughter] this one kid or this, you know, these two kids that have paternal, you know, father mitochondria." Turns out it was

father mitochondria." Turns out it was like a mistake in the sequencing or >> so mothers are truly always right.

[laughter] >> Yes. Power to power to mothers. people

>> Yes. Power to power to mothers. people

will be thinking and I'm also thinking does that mean and of course there are lifestyle issues but does that mean that if we were to look at the quoteunquote

energy levels of mom versus energy levels of dad that what better predicts the energy levels of a kid is the mother's sort of baseline levels of

energy at a given age >> I don't know the of studies that have asked that question about like subjective energy or like the energy to do stuff and uh which we I think we'll

talk more about but uh people have looked at other more uh tractable which what we do in biio medicine we take things that we can measure objectively or like you know run on a gel or

sequence or you know objectify with a biioarker in in the clinic uh people have looked at longevity right are are you more likely to live long if your mom lived long or if your dad lived long.

Turns out the heritability of longevity is more maternal than paternal.

uh or are you more likely to have a mental health disorder or to have Parkinson's or Alzheimer's if your mom or your dad had it? Uh some evidence say it's more maternally inherited than

paternally inherited.

>> Uh so it could be that part of uh the your ability to live a long healthy life uh or your risk or your resilience right to those disorders really are conveyed

or carried by mitochondria by your ability to to transform energy. And the

the reason why through evolution uh unique parental inheritance you get your mitochondria from a single parent uh has developed most people think is because there needs to be a really close

metabolic energetic match between the mom and the baby right like the baby comes out and then if the mom has like a certain type of metabolism and we're all different I hope we talk about like how

different we are energetically metabolically uh so we're all very different if the baby that was born was like so metabolically different than the mom, there's a chance that there would be a mismatch, right? And then the mom

wouldn't be able to support through breastfeeding. Historically, that's how

breastfeeding. Historically, that's how babies survived. Uh, and that would be a

babies survived. Uh, and that would be a catastrophe. So, you know, it's probably

catastrophe. So, you know, it's probably a good uh system to have baby metabolism match pretty closely because they have the same mitochondria as the mom to mom

metabolism. Uh, so that's I think a

metabolism. Uh, so that's I think a loose hypothesis, but it makes a lot of sense.

>> It does make a lot of sense. Yeah, every

mitochondria you have in your body, like the brain mitochondria, neuron mitochondria, astroite mitochondria, whatever your favorite cell type is, your heart mitochondria, liver mitochondria, muscle mitochondria, they're they're very different. And now

we have a new method. There's a

wonderful scientist in her group, Anna Monzel, who's developed a method to profile different types of mitochondria.

We call this mitotyping. The same way that now in neuroscience or in immunology, it makes no sense to talk about a brain cell or like an immune cell right?

>> If you're a self uh you know respecting immunologists, you know, your cell types and there's, you know, at least 30 different types. Uh so I think we're at

different types. Uh so I think we're at this point in mitochondrial science where we need to adopt a similar level of specificity. There are different

of specificity. There are different types of mitochondria. We call those mitoypes. uh and they emerge all of them

mitoypes. uh and they emerge all of them from the same mitoype in the egg right the the egg that the mother carries and you know releases from the ovary there's

about half a million uh mitochondria in that egg uh and then those mitochondria there's a single type of mitochondria in there and then when it's fertilized

development happens in this beautiful uh process and through that process as the heart starts to form the brain starts to form the muscles start to form the mitochondria differentiate and then you end up with different types of

mitochondria that are adapted and matched to the different demands of of of cell types of organs. uh and one way we think about this is I think it's uh

it makes a lot of sense to think about mitochondria as social organisms >> and there multiple features of mitochondrial biology that obey you know

what u behavioral social scientists you know classify as as social you know if you study ants for example there's like a few rules that we know ants are social creatures because uh they form groups

right and there are different types they they divide there's division of labor you have worker ants that, you know, work really hard and you have a warrior ants that are like really chubby and like they're they're here to defend the

the hive. They like to fight. Yeah.

the hive. They like to fight. Yeah.

Exactly. So, those two types of ants, you look at them side by side, there's like this little flimsy super like uh uh active worker ant and then this like chubby uh warrior ant. Genetically,

they're they're identical.

>> They have the same genome. They came as, you know, little larae from the, you know, the queen. Uh but their their morphology is super different. behavior

is is very different. Uh but through development there are cues that you know are are um uh uh applied to the different larve and then they end up

becoming a worker or a warrior. Uh so

the same kind of thing happens uh in in mitochondria. So mito there are

mitochondria. So mito there are different types of mitochondria like the two types of ants. There's division of labor. There's some mitochondria for

labor. There's some mitochondria for example in the muscle that are at the surface of the muscle like just underneath the saroma the the skin of the muscle cells and then there mitochondria that are inside you where

the actin measin the contractile proteins happen subscar mitochondria and interophibrillary mitochondria two populations their proteom is different their their molecular composition of

those different types of mitochondria are different their functions ATP synthesis reactive oxygen species production their ability to handle calcium and release calcium is

different. Their morphology is very

different. Their morphology is very different. So even within one cell you

different. So even within one cell you get this uh division of labor and um uh differentiation of mitochondria and in every cell mitochondria have a life

cycle. New mitochondria are born and old

cycle. New mitochondria are born and old mitochondria die out uh which is what happens in social creatures. Um and

there's a few other features like this that I think make mitochondria social organisms. And once you start to think about mitochondria as social uh creatures, then you understand maybe a

little better why they need to fuse with one another. And if you if you ask

one another. And if you if you ask Google what do mitochondria look like or chat GPT or whatever, uh the it shows you always the same kind of images. It's

like a little bean.

>> I brought one you brought one as a gift.

I at one moment I thought they might be brass knuckles when you hand first handed them to me, but I said mitochondrian with the ce of the mitochondria. usually looks like this.

mitochondria. usually looks like this.

But you're saying in in reality there'd be many of these connected to closely fused to one another.

>> Yeah. So, and when they fuse, you get these like bean or kidney shapes or peanut shape, whatever your your preference is that fuse with one another and then they form these beautiful filaments. Uh so, if you're lucky enough

filaments. Uh so, if you're lucky enough to work in a lab that has one of these cool microscopes called conffocal microscope or light sheet microscopy and then you can make the mitochondria

fluorescent. So you put a dye in in the

fluorescent. So you put a dye in in the dish and then it's a little fluorescent molecule that it goes inside the mitochondria. It's attracted by the big

mitochondria. It's attracted by the big uh charge that mitochondria have uh and then you turn off the lights, look down the eyepiece and then you see this beautiful like filaments, you know, mitochondria moving. They move pretty

mitochondria moving. They move pretty slowly and interestingly they're just at the edge of human perception of like uh how quickly we can perceive things to move. So they move like, you know,

move. So they move like, you know, barely fast enough so you can see them and then they they they kiss uh and and then confuse completely.

>> Either you can invite everyone to your lab to see this, but that's a lot of people. You'd be very busy. We'll put a

people. You'd be very busy. We'll put a link to a video of this.

>> Um >> we're we're building a web page called Mid Life, uh which is to help people, you know, understand themselves energetically uh and through, you know,

the beauty of mitochondria. And there

are all sorts of different types of mitochondria that move differently. And

when the mitochondria are are not healthy and if they can't flow and transform energy properly, they start to look really weird. [snorts] It occurred

to me that, you know, for the longest time, I'm 50 now, so I can say for the longest time. For the longest time, we

longest time. For the longest time, we heard that if we want energy, we need to eat, right? Of course, we need to sleep,

eat, right? Of course, we need to sleep, but we need to eat. So be like and and every kid learns you're consuming energy that so that you fuel your body there all these discussions you should eat

meat don't eat meat I believe you should eat some meat you should eat some vegetables some fruit etc I think you should be an omnivore some fats yes that's my my belief but we all

understood that but then at some point probably about 10 years ago it became clear to people that just consuming more energy didn't give you more energy it

was an obvious thing but it's now abundantly clear and based on what you're saying, it should be clear to everyone that the issue is not lack of

energy going into the system.

>> It's that the transformation of energy that occurs in mitochondria somehow is not happening correctly in people that are obese um or in people that are eating and feeling lethargic. And of

course, there's blood sugar, you know, aspects to this and we could discuss all of that and we won't because that's not the topic for uh for today. But I think if nothing else, if people can just

understand that they have not just these powerhouses, but these power plants within their bodies that are transforming the energy and that the mitochondria are central to how the

energy is transformed and distributed >> on an organ byorgan basis.

I think that would be a helpful concept for people to get into their mind because people are talking about mitochondria all the time. People are

talking about and hearing about nutrition all the time and so often we just think about calories and you know everyone knows that you know calories is a unit of you know heat offput when you burn a given food and we learn this

stuff but it doesn't transform into good health practices >> but I think nowadays people are starting to get a sense of of how their bodies work and you're adding a lot of important uh detail and aspects to that

today.

>> Um so I just want to frame that up. Y

>> um if you have any reflections on that great if not it was just a point that came to mind that I think it might be useful. Yes, it's so important and we

useful. Yes, it's so important and we are energy fundamentally we are the flow of energy through this biological infrastructure right that we call the body but you are not the cells or the

genes or right that that thing you are much more uh that energy that is flowing which is why when the energy stops flowing you are no longer when you die

all the phys physical stuff remains but you you no longer have an experience you no longer exist as a as a person >> the way I think about this is rather than thinking in nouns, think in verbs.

>> And I think as biologists when we teach biology, you have to teach some nouns, some names of things. But if you can get people to understand the verbs, as concepts,

>> it's worth a a gazillion nouns.

>> And so I think um people thinking about themselves as a verb state >> of as energy transformation being, it sounds so mystical, but it's not mystical. It's biochemical. it is

mystical. It's biochemical. it is

>> uh I think could be useful. Along those

lines, I I do want to um talk about this recent paper that you uh published uh which essentially my understanding is

that looked at different brain areas and found that different brain areas have different concentrations of mitochondria. And we know that different

mitochondria. And we know that different body areas and different organs have different concentrations of mitochondria. But I heard you say

mitochondria. But I heard you say someplace and this is such a beautiful sticky topic as they say that perhaps the things we do in life

>> maybe lift weights, maybe study biology, maybe play the piano, maybe some combination of things >> will enrich the mitochondria, these energy transformation sites in particular organs and areas of our brain

more than others. And so we really become what we pay attention to. We become

enhanced for what we do. And that makes sense at the level of endurance runners run and their muscles become and everything becomes optimized for running. Weightlifterss something else.

running. Weightlifterss something else.

But in the brain, this gets very interesting. This means that if we read

interesting. This means that if we read poetry for instance or study biology that the areas and circuits of the brain that are responsible for that in some sense become better at doing that. Mhm.

>> And I think this is a very important topic because it really gets to the essence of who we are as individuals based on our choices of what to do and what not to do.

>> So with that as the backdrop, if you could tell us about this paper and tell us about what you think about these findings and what they might mean, >> I I would love that.

>> We flow as energetic processes, right?

To to your point like we we are transformative processes. Like we

transformative processes. Like we transform, we flow. We are the energy that flows. And the more you direct

that flows. And the more you direct energy to one area, right? If you go to the gym and you do bicep curls, like you're resisting the flow of energy while you're contracting and then you do this a few times and then when you let

go, you get like blood flow, right?

Energy flow through the system. Uh and

we know exercise training is a beautiful example. Like if you train to run a

example. Like if you train to run a marathon, for example, you can double the number of mitochondria in your muscles. Wow.

muscles. Wow.

>> Double, right? And my understanding of this is as energy flows through the existing mitochondria you're basically bringing you know energy into that that system and then this uh that the

biochemical energy gets transformed and into molecules into metabolites and then eventually into proteins and then structure gets created as energy flows right so it's the flow of energy first

you resist it that's we call this energy resistance and and then when you let go of of the resistance it's that's when we build. That's when we grow. That's when,

build. That's when we grow. That's when,

right, Arnold Schwazer said, um, muscles are torn in the gym. They're fed in the kitchen and are, um, grown in bed, I think is

um, >> in an Austrian accent.

>> Yes. So, um, so yeah, if you direct energy towards a muscle, right, then one way to direct energy is to resist the energy flow and then to to let go. And

that's what exercise fundamentally is, right? You resist the energy flow and

right? You resist the energy flow and then you let go. When you resist energy too much, it feels uncomfortable which is like the the burning pain of of and then when you let go is when growth and

uh you know building can happen. Uh and

we know the same thing happens like everywhere. This is this is not like a

everywhere. This is this is not like a mysterious thing of the muscle and like of exercise uh you know physiology. This

is a fundamental biological principle.

If you flow energy in one area then it will grow. It will you know get better.

will grow. It will you know get better.

it will get more efficient. And if you block energy flow to one area like you block blood flow for example or you get an accident and the nerve gets you know damaged then the the muscle doesn't contract anymore you're basically

blocking the flow of energy there and what happens it atrophies right atrophy is a normal uh movement of life when energy flow decreases and if if there's

no energy flow really there's no purpose for that structure if you feed if you stimulate that structure be it a muscle or brain circuit, right? A brain network

or brain area. Uh then naturally, you know, that that area should uh should grow and and and build. Uh and there what we know happens in the brain and also happens between different organs of

the body is there's kind of a competition for finite energy resources.

>> Right? What you said earlier like you can't just eat more to get more energy.

We know now we know very well if you overeat, right? you eat more than your

overeat, right? you eat more than your body is actually flowing consuming in terms of energy transforming you get sick like if you can you put on fat

which is a good adaptive uh coping mechanism to eating too much uh but then eventually the systems like it gets overwhelmed and then that hurts the mitochondria and it hurts you know

cells to become insulin resistant and so there's all sorts of consequences to eating too much you cannot eat more to get more energy and that is I think still scientifically a very big mystery,

right? That why can't we just ramp up

right? That why can't we just ramp up our energy uh consumption, energy transformation and then like sleep less and you know uh work out 3 hours every day that even

like professional athletes who devote all of their energy to you know building muscle mass, building skills or you know building aptitudes, there's a limit to how much you you know you can eat. Uh

and they're they're yeah we don't really know why that is why there's a limit to that. And uh so the body operates an

that. And uh so the body operates an economy of energy. You have x amount of energy. You can push that up, you know,

energy. You can push that up, you know, over short periods of time. Like if you start to work out and you're you're a cyclist, you do the to France, right?

Like three weeks, you're you're going for like five 7,000 calories a day. You

do this for three weeks. There's a

reason why the to France is not four weeks and five weeks, >> right? There there's there's a cap. And

>> right? There there's there's a cap. And

there's beautiful data showing that the longer the event the athletic event the lower the max output per day and and if you looked at that curve you know the

the first point max power output you can develop over 10 seconds is what you see in the 100 meter sprint right and then you get the uh 400 meters and and then it goes down at the very and the to

France is you know marathon is here to France three weeks is here then you get like crazy run across America multiple weeks and then at the very end nine months pregnancy

and [snorts] it costs energy to grow a human being and uh some of the data suggest that when you grow a human being for 9 months you're basically operating at the max of her capacity if you integrate over you know a 9-month

period.

>> Do pregnant women accumulate more mitochondria or the energy demands are entirely for the mitochondria of the developing fetus?

>> That is a good question. We know certain brain areas grow during pregnancy >> that the brain remodels. Exactly. Uh

there are different demands, right? As a

mother, if you're pregnant now, you need to start to care about different things.

>> Maybe it's adaptive to start to think about the world slightly different way.

And it's not just just about yourself.

And >> um so there there are certainly and even long-lasting brain changes happen in in the woman's brain. So this economy of energy between organs is likely what

explains if you're a young woman and you exercise a lot, you lose your menes, right? Aminora, then this is not because

right? Aminora, then this is not because the the reproductive system is broken or because the ovaries are or are sick or something like that. The best

explanation we have is there's a short shortage of energy. Like you're pushing and driving all of your energy budget towards your working muscles towards making more mitochondria in your muscles

and there's no more energy to fuel to to to fuel uh reproduction. I have a practical question related to this.

I have always wondered why is it that when we're coming down with a cold or a flu or some sort of other infection that there are a bunch of processes that make us uh more lethargic and tired and these

are very adaptive and we know we need to rest. But it's not just about getting

rest. But it's not just about getting sleep. We actually need to slow our

sleep. We actually need to slow our circulation down. We need to rest.

circulation down. We need to rest.

>> And there all these theories, you know, about do you feed or starve a cold or flu. And I covered that in a different

flu. And I covered that in a different episode. We'll put a link. It's not

episode. We'll put a link. It's not

straightforward, but um follow your appetite, stay hydrated, keep your electrolytes up and so forth is the short answer. But is it that the immune

short answer. But is it that the immune system needs more energy and the body as a protective mechanism, as an adaptive mechanism is saying slow down everything

else and devote yourself to uh healing, to fighting this infection as opposed to spending energy even walking up the stairs as much as you typically do during a day. Is that the is that the idea?

>> Yep. I think that's the best model we have. Uh and I had a personal experience

have. Uh and I had a personal experience of this uh over a New Year's a couple years ago where I I could feel I was, you know, coming down with something uh before the, you know, New Year's dinner.

And so it ended up being a pretty short night. I went to bed early and that

night. I went to bed early and that night was terrible. The next day I was so uh so off and I was, you know, starting to work on on the book Energy and then I thought, "Oo, this is such a

a cool opportunity." Like now I'm experiencing I'm feeling drained, right?

Like I'm in bed, everything hurts. And

then I thought I should be writing about this, right? Like and then I I thought

this, right? Like and then I I thought like just the the thought of like grabbing my computer then I shouldn't cost more doesn't cost a lot of energy just like wiggle my fingers on the

keyboard. But you know there was no

keyboard. But you know there was no drive. I stopped caring about stuff that

drive. I stopped caring about stuff that I usually care about, right? Everyone

has experienced this when you're really sick.

>> Uh motivation, right? zero. Um, my

capacity to be the best human being that that that I am and to be kind >> a little diminished.

>> Just like [snorts] I was just >> trying to survive, you know, like and and what we know in terms of biology and mitochondria and energy that happens when you're fighting something like this, the immune system cost a lot

of energy.

>> Mhm. Uh so I think the best model interpretation we have of sickness behavior is what you were describing the technical term is you feel sick right and you don't want to move the body you

feel cold right which then uh forces you to put covers or you know to to dress to avoid cold environments uh you it it hurts to move your body like to contract

muscles and like the the there's alodmia right the sensitiz you become more sensitive to pain all of these things uh likely exist in service of conserving your precious energy budget and even not

eating right like follow your appetite.

Yes. And and if you you know eating costs energy nothing in biology is free.

Everything costs something. And if you eat food now you need to masticate. You

need to like have peristelsis. You need

to have gastric acidification movement you know secretreting digestive enzymes and maybe some bile. Like there the the orchestration of digestion is pretty expensive. It's like 10 15% of your

expensive. It's like 10 15% of your daily energy budget. So that's a 10 15% of your daily energy budget if you're running like a limit is a lot. By now

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drinka1.com/huberman to get started. You mentioned that if women exercise beyond a certain threshold, uh they stop menrating and that it's because there's not enough

energy essentially to menrate. One idea

would be well if you just eat enough then you have enough energy. But we have to think in verb states not absolutes.

And so what I'm realizing is that while one needs sufficient energy input in the form of food and this could also be true for the example of being sick, >> it's necessary but not sufficient

because the mitochondria are doing two things. They're transforming that food

things. They're transforming that food energy into bodily energy to menrate or to move or exercise or think or care about a book etc.

>> But part of their job is not just to transform the energy, it's to distribute the energy. And so you really need two

the energy. And so you really need two conditions and you know I'm not a computer scientist but I know enough about programming you know and engineering that you know this concept

of an andgate you need sufficient energy so coming into the system and you need to be able to distribute that energy properly in order for something to occur it's an endgate you need both things basically

>> so I now and forever going forward will think about mitochondria as not just energy production but energy distribution organal Yes, >> thanks to the way you described it. And

now it makes perfect sense as to why when I'm sick, if I'm not hungry, I'm not going to force myself to eat, provided I have enough body fat stores, you know, I need to eat eventually, but

whatever weakness or fatigue I feel is probably in that situation where I don't have an appetite is probably not a lack of caloric energy driving that fatigue.

It's that my body is saying, you know what, you're better off just not having me shuttle that food energy through you so I can shuttle your immune cells to the proper place. Exactly.

>> And this is when people say the body is smart. There's an intelligence to the

smart. There's an intelligence to the system. I think that's true because with

system. I think that's true because with our brains, we think, oh no, I'll just cram more energy into you need to eat.

You need to No, maybe not. Whereas if I do have an appetite, I don't care what people say about feed a cold, starve a flu or feed, you know, starve a flu, feed a cold. I'm just going to do what my body tells me to.

>> Yes. Yes. And I I agree the body is wise. Animals who don't have a very

wise. Animals who don't have a very other non-human animals like your dogs uh like they they don't have a mind to distract them from, you know, living in

alignment with their energetic states.

>> So when they're sick, the immune system just the the amount of the the part of your budget that gets consumed by the immune system, you know, expands, right?

So this energy this extra energy needs to be stolen from somewhere because you can't eat more to have you know infinite energy. Uh so what where's that energy

energy. Uh so what where's that energy coming from? So not contracting your

coming from? So not contracting your muscles because you feel in pain is a good way. Not having to thermmorreulate

good way. Not having to thermmorreulate because you you know cover up another way to conserve energy. and then

stopping to care about stuff like becoming asocial and apathic and all of those features of sickness behavior or energyconserving

uh strategies and not eating like if you can have like free 10 15% of your energy now you can allocate it to your immune system that is a very good strategy most

people walk around with multiple weeks if not months worth of energy right like under the skin and their love handles uh the record actually for not eating is

from this uh Scottish man. 382 days.

>> Was he fat when he started?

>> He was very fat.

>> Was he fat when it ended?

>> Uh he lost uh how much he lost like 250 lbs I think.

>> That's all stored sandwiches.

>> Yeah. So most people can eat can go a full month without eating. So So and this maybe goes back to what we talked

about earlier like we don't feel energy quantity, right? Like uh if you close

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 to feel our energy.

>> Definitely.

>> Yeah. Okay.

>> By the way, a a a tenure full professor at Columbia School of Medicine just said, "Uh, do you want to do a little experiment to feel your energy?" and we both closed our eyes, which tells you that it's definitely 2025. [laughter]

>> You know, the reason >> good things have happened in the world.

Okay.

>> The reason we both closed our eyes and kind of stopped moving our our bodies, which is kind of what you do if you want to meditate or something like this, is because it turns off the noise.

>> Mhm.

>> 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

you, right? Or kill you. Um and feeling your body like propriception and all of this needs to be very high level. Yeah.

It needs to be prioritized over whatever intraceptive you know signal there are.

There's some intraceptive signal that's what we'll feel into that you know can overcome that but just not moving the body closing your eyes it kind of helps you to tune into your energy and I

suspect there's a lot of value there.

>> Yeah. We'll talk more about some incredible results about meditation and and restoration of energy. Um, can the audience do this along with us provided they're not driving?

>> Yes. Yes.

>> Okay, great.

>> Yeah.

>> Uh, so to do this, uh, best is you're sitting comfortably and, um, you can close your eyes if you want to. I think

that helps with the the process. We'll

take one breath in and then, uh, we'll we'll hold the breath for a little bit.

So, breathing in, [snorts] breathing out, and you can breathe out all the way, all the way down. And then hold that breath.

And for the first few seconds, it's generally not too uncomfortable. But

then as you hold this, feel into your body, to your belly, into your chest, into your head.

What's the effect of not breathing? And

then you start to feel maybe this urge to breathe and this desire to bring oxygen into your body, to your mitochondria.

And then when you need to, you take a breath in. You can open your eyes. If

breath in. You can open your eyes. If

you can hold it longer, you you do.

Yeah. What did you feel? So when I went to the full exhale and held my breath, >> uh my what we geek speak, what neuroscientists call interosception, my

perception of things from the skin inward became more salient and I could feel my heartbeat uh more and more. Um,

and then it didn't speed up, but I could just feel my heart beating. I was more aware, excuse me, of my heart beating.

And then I, as the impulse to breathe started to kick in, uh, you could feel a bit of ramping up of it's not anxiety, but it's a sense of urgency,

>> you know, hardwired, fortunately, sense of urgency. And then with an with an

of urgency. And then with an with an inhale, there's a a relaxation of of that sense. Y

that sense. Y >> and um there is this sense that uh energy moves out from the center at that point like like you feel more of your body

>> because I think anytime we don't have air um our brain goes to how do I bring air right here right now you're not thinking heartbeat you're thinking get get air >> something of that sort

>> yes I think if you do that and the the the urgency right the anxiety the stress or um this you know it feels dangerous

right and And I think to many people dying by drowning or like suffocation is like the the the one of the worst death.

And uh so why is that? Like what is that sense of urgency of anxiety? It's CO2

building up in your blood. Right? CO2 is

the product that mitochondria release as they transform energy. And then when CO2 builds up, it means oxygen is getting depleted. Right? If oxygen gets

depleted. Right? If oxygen gets depleted, the electrons from the food you eat can no longer flow. Right? If

there's no oxygen at the end in your mitochondria to accept the electrons flowing, you stop flowing. So you as a movement of energy are at risk of of

ceasing to exist. Not being able to breathe, right? Uh being out of breath

breathe, right? Uh being out of breath is an existential threat to your energetic self. Without getting into the

energetic self. Without getting into the details, I've talked about it on other podcasts. I had a a scuba diving

podcasts. I had a a scuba diving accident a few years ago, 2017. ran ran

out of air in a >> in a bad situation to begin with. Um and

I'll tell you the sense of urgency is very immediate and um fortunately didn't end up with any PTSD from that. It

obviously worked out okay. I'm I'm

sitting here and talking. But um now I understand why. And I never did this to another kid, nor did anyone ever do it to me, but there's this joke that kids play on one another where their friend is coming up from underwater and

you're ready to take a breath. That's

why you come up from underwater. And if

someone holds your head right at that point, even though it's just a m a moment, >> the sense of urgency that kicks in >> is very intense and very very fast.

>> Uh which speaks to just how hardwired these circuits are because at that point presumably there was enough air to stay under for another 5 seconds or whatever it is. But when we anticipate getting

it is. But when we anticipate getting oxygen and we don't, >> there's a big increase in >> stress. energy goes straight to whatever

>> stress. energy goes straight to whatever whatever areas of the brain, amydala and other areas presumably that are like this is a bad situation do anything and everything becomes about resolving this situation.

>> Yes. And and that's because we are energy. We are the flowing energy

energy. We are the flowing energy through the system. And if energy uh starts to stall, it just feels so uncomfortable. We have to have evolved

uncomfortable. We have to have evolved to to feel this. If something is making your energy stall, like there's not enough oxygen around, you need to get out of there. And you need to have this instinct, right, to to survive. So,

what's trying to survive is not like the the physical body. It's it's the this flow of energy that's, you know, being threatened, right, from from lacking oxygen.

>> Many times already, you've talked about the flow of energy, and that concept, I think it's going to be threaded through as we go forward. when you hear about um practices

like Tai Chi or when you hear like in the martial arts where people are taking other people's energy and you know converting and this is a not just a thing of like of iikido but the notion that like if you box you learn that you

you're not just hitting with your arm and your shoulder you have to keep your feet planted you're pulling from the floor in some sense you're transferring the energy but you're actually pushing back against the floor and then it's coming up through your body people talk

about the fascial slings you know when people run there There are a bazillion different variations on this, but it's all about this concept of flow of energy. And I find that so much of what

energy. And I find that so much of what we find incredible when people dance, when people uh sing, when people uh do incredible athletic feats or channel

everything they've got into something.

This channeling of energy is the human animal deliberately channeling all their energy in the form of practice into something. In many ways, we love that.

something. In many ways, we love that.

Even though by definition it creates a very uh lopsided person and I I'm not trying to get into the psychology of this so much as I want to go back to this notion of our brain areas having

different amounts of mitochondria >> probably from birth but then if we play soccer and we like math and uh pottery we get a different brain

>> than if we like reading and theater and movies and We'll exercise, but we're not too crazy about it. You know, if we exercise, our brain works better. We've

heard, >> but there's also the notion of the person who just spends all their time exercising >> and their brain doesn't get better.

>> I'm being gentle there.

>> And I like exercise and I like thinking.

[laughter] So, >> is there a trade-off?

>> Is there a trade-off?

>> Because I believe in staying fit and staying healthy and living a long life, but most people are not competitive athletes. Most people don't want to be

athletes. Most people don't want to be the strongest person in the gym or the best runner. Most people, I believe, and

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

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

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

life. I don't want to become the atrophied >> in one area and hypertrophied to some great extent in some other area, human.

>> Yep. So, what are your thoughts on these through the lens of the results that you recently published?

>> Is it a trade-off? I don't think we know uh exactly, but we did a study recently that points to the fact that there might be trade-offs >> between different systems. >> Sorry, meattheads. No, I'm just kidding.

I love I love working out in the gym, but you have to read too, you know.

[laughter] >> You know, we we tested the hypothesis that if you have more mitochondria in your muscles, you also have more in your brain and then your heart and then your liver and then your skin. And the result

is that's not the case.

>> And you know, you Andrew, I think you seem to derive a lot of fulfillment. And

um you know, you live up to your full potential when you can do all of these things, right?

And you're a great communicator. You're

a great integrator. You know, the kind of thinking you do is like this this beautiful integrative thinking uh which is which might be what has led you to do what you do now, right, for with most of

your time because this really taps into your strengths. It really moves you, I

your strengths. It really moves you, I suspect, energetically. I think I enjoy

suspect, energetically. I think I enjoy it. You enjoy it. What does that mean?

it. You enjoy it. What does that mean?

Right? Enjoyment is kind of an emotional state, an affective state that it's an energetic state. We're all different

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

gifts. I think we we're born with something that uh doesn't seem to be fully just encoded in in people's genomes. [laughter] there are

genomes. [laughter] there are genetically identical twins that have very different aptitudes and you know personalities and we don't know where this comes from. Um and and then we are

fed we're you know moved and inspired by different things and uh when people seem to follow that it it appears to bring them energy and what this means biologically the level of mitochondria I

think our our research is starting to to point in a direction that says if you're engaged in things that bring you purpose and fulfillment there's another study we

did we asked people our colleagues in Chicago ask people before they died. How

do you how much uh sense of purpose do you have in your life? How meaningful

social connections, well-being, right?

Uh and then the negative stuff, depression, loneliness, you know, anxiety, uh and then every year they answered those questionnaires. So, we

knew how deep people felt about themselves, about life, about, you know, some greater power, you know, beyond them. Uh and then they died, gave their

them. Uh and then they died, gave their brain to science. We got a little piece of brain and now we're measuring the mitochondria. uh and Cavalyn Trump uh a

mitochondria. uh and Cavalyn Trump uh a researcher who works in her group who's a a bonafide mitochondrial psychobiologist. So she asked questions

psychobiologist. So she asked questions between the psyche and and the and the biology of mitochondria. So she asked could it be that how people felt before they died relates to the bitochondria in

their brain and the prefrontal cortex the DLPFC the dorsalateral prefrontal cortex. And what she found is that

cortex. And what she found is that people who felt more purpose in life and who felt more connected to others and who felt you know well-being uh for whatever whatever was bringing them

well-being it seemed like that was sufficient to increase the energy transformation capacity of the mitochondria in their brain. So is this because of the experiences that you know

they're fortunate to have or that they're actively fostering in their life uh that's actually transforming the mitochondria in their brain maybe. Or

it's the other way around for some reason that we don't understand they have more of the energy transformation capacity in their brain mitochondria and that is leading them to experience the

world as more positive and as more purposeful and as more meaningful.

Right? Animal studies say it probably goes both ways. So if you tweak the mitochondria in a rat brain, you can change the behavior of that animal to from more submissive to more dominant or

from more dominant to more submissive.

Beautiful work by Carmen Sandy at EPFL in Switzerland that showed this. Uh and

then the other way around, if you chronically stress animals, you deprive them of kind of freedom of choosing different, you know, options. So

chronically stressful things actually damage the mitochondria in the brain.

And there in some brain areas there are fewer mitochondria and they don't transform energy as well. So the

mitochondria are responsive it seems to our states of mind. Uh and that the mitochondria in our brain can also influence our states of mind. And and if if we want to talk about the philosophy of this thinking about like what's

causing what maybe is and you're really the right question to ask but what's emerging is that's relevant to your question. There's a clear connection

question. There's a clear connection between the subjective experiences that we have that we know from first person to be meaningful, right? Because that's

what we have access to uh primarily is how we feel, how we experience the world somehow is related to the biology of the energy transforming units, energy processing units in our brain, >> man.

>> Uh and and maybe also in our immune system. And so we've done work in immune

system. And so we've done work in immune cells and in brain tissue. Um, and we're currently analyzing mitochondria from 5,000 uh human brain samples. That's 10

different uh brain and and muscle uh samples from 500 people.

>> Do you have histories on these people as to how much purpose, what they did, how life how much life fulfillment they had.

>> I'm so glad that biologists like you exist. I just want to say that uh not

exist. I just want to say that uh not just because you're agreeing to be a public health educator, but um just it's incredible how much things have changed in the last few years in terms of the

public awareness about biology and psychology. But I I have the genuine

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

medical school. But you're merging these ideas in in real data. And I think it's going to bring together ideas that have been in cooperation for a long time but didn't realize it. And I think it's

going to transform human health because >> if we think about ourselves as energy transformation beings, we're going to think pretty carefully about where we invest our time and energy and also I do think start to

listen to our bodies more when we're feeling shut down. Like what does that mean?

>> You know, uh now we can't respond to everything as just a well does it give me energy not give me energy because we also have to build up some circuits to be proficient in life that perhaps

>> are inconvenient for us to build up.

But at the same time, >> I think there's a lot to be gained from this idea of does something give me energy. Does this

energy. Does this >> I think people uh confuse like drama and friction with certain people. It's like

that's energy expenditure. That's not

that's not good transformation of energy. And you hear about this stuff

energy. And you hear about this stuff now more in the psychology relationship space. People will say, you know,

space. People will say, you know, they're not good for my nervous system.

It's so funny how neuroscientists now, you know, where or I just feel relaxed around them or I can sleep next to them so comfortably. And you know, we kind of

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.

that's cute. That's kind of woo. Uh-uh.

This sounds like real biology if pushed through the lens of what you're telling us about mitochondria as energy transformation units.

>> Yep. I think everything you just mentioned doesn't make much sense from this molecular biology lens that's really captured biio medicine, right?

like many years ago, 50 years ago or so, like there was this wave of whoa, there there's DNA that exists and there's, you know, proteins, we can sequence stuff.

We can measure, you know, uh the components of a cell and we can look at things under the microscope and we can, you know, scan the brain and like all of those um um assets that we were, you

know, all of a sudden able to to capture. It was really convincing,

capture. It was really convincing, compelling. We built a whole research

compelling. We built a whole research and you know academic science ecosystem around this and I think as a um by by

nature this reductionistic framework pushed aside the mind right the the all of the subjective experiences you know it's in your head or you know whatever all of this was pushed aside so the

human experience is the most direct way in which you can know whether the content of your life matches your your energy right and matches what matters

for you and uh and what you really care about. Uh so like pushing aside which is

about. Uh so like pushing aside which is what biio medicine has done pushing aside the mind and all of those subjective experience I think has been really um damaging to understanding the

basis of health and understanding what allows some people to be healthy for like really long time and to live long healthy lives and to live you know fulfilled lives. um we we if we if we

fulfilled lives. um we we if we if we think of ourselves as molecular machines like there's no way we can make sense of this and then we have consciousness you know research that's trying to make

sense of of these beautiful uh this beautiful spectrum of human experience right from like I can't get up in the morning like taking a shower is like too

difficult and I'd rather die like this is one end of the spectrum and then the other end is oh my god the world is so beautiful I'm so grateful I feel

inspired to be a good person um and I can do good in this world, right?

There's and then everything in between and we're left now we don't have a science of this like we've we've said this is not science, right? This is like psychology. This is woo stuff and and we

psychology. This is woo stuff and and we can't access this with biomolecular science. And I think it's true. I I I'm

science. And I think it's true. I I I'm not uh I don't have a lot of hope that we will make great inroads in fully capturing the nature of consciousness,

the nature of the human experience, the nature of well-being, of what it means to be a fulfilled human being that lives up to their full potential. I don't

think at the at this point that we'll find answers in molecular biology. But

what I do think is that an energetic understanding of life and an energetic understanding of ourselves, right? As an

as a flow of energy, not as a molecules and the metabolism that support this flow, but as the flow itself. I think

that is kind of a point of consilience.

Energy flow is the lynch pin between matter, you know, the stuff of biology [laughter] and experiences. Again, we

don't experience energy itself. If we

experience a transformation of energy when energy flows through this metabolic circuitry that we have, metabolism is just an energetic circuitry. Electrons

flowing not as free electrons in a a copper wire but as electrons from food to oxygen through enzymes. Right? So

this thing is a a metabolic carbon-based you know energetic circuit. And when

energy flows through this somehow for reasons we don't fully understand it feels like something right and emotions energy in motion subjective experiences

of feeling inspired and and doing good or feeling terrible wanting to die like these states all live and all emerge from the transformation of energy.

Energy is kind of that consilience point where we have you know behaviors uh everything we do in neuro imaging right the EEG whatever when we look at the brain we're really looking at energy patterns if you just change how much

energy flows in one region or another you change the anatomy you change the biochemistry and then that gets encoded if energy flows a certain way or is patterned a certain way it will change how genes are expressed right it will

change the epiggenome because of metabolites and whatever intermediates are are there >> I'd like to take a quick break and acknowledge one of our sponsors, Function. Last year, I became a Function

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think has been missing in this whole landscape of health frankly has been somebody who understands the different levels of analysis. Uh a

great neuroscientist at uh now at NYU once told me that a a real intellectual of which you are is somebody that understands and can communicate something at multiple levels of granularity. That's very very important.

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

behaviors. I think what we just touched on here is like mitochondria flowing transforming energy and then that energy kind of ripples out >> at the level of the cell and their

metabolites that are mitochondria are producing based on the energetic state of the mitochondria. there will be more you know acetyl coa and citrate and uh lactate and alpha ketoglutarate and

those are all you know molecular uh imprints of an energetic state and then those molecules carry this energetic signature that's in the mitochondria to the nucleus and then boom they get

written down as the epiggenome and now the cell all of a sudden has this gene turned down turned off or this other gene turned on and now the cell is a different kind of cell >> because there was a change at the

energetic level in the mitochondri And then that ripples out. Now the cell, you know, experiences its environment in a certain way energetically, right? That

starts in the mitochondria, ripples out to the nucleus. Now the nucleus is able to make proteins like cytoines. And so

cytoines in many ways are uh signatures of an underlying energetic state. So

what we call inflammation, my understanding of of inflammation is it's an energetic state. And in many cases is if the energy doesn't flow freely or you

know with low resistance in the system if you're a cell and either you're running out of oxygen right you're hypoxic electrons can't flow as a cell you know you have this primal experience

of what you experienced earlier right you're not breathing you're like I I have to take a breath or I'm going to die >> so if you're a cell and you experience a version of this a really primal version of this you need to do something

>> so you call out >> you call out you call out for help and that's where the cytoines come in.

>> Yeah, cytoines are, you know, universal language of cell cell communication.

>> Cytoines are not immune. They're they're

there this you know fundamental way that cells have to talk to each other.

>> Assuming that it is this repeating set of principles of of energetic flow.

Let's get a little woo for a moment.

Let's get really woo for a moment. We

are in California. Uh because I am beginning to understand it's grounded in real biology. For instance, people have

real biology. For instance, people have heard of the 27 club. You know, you have there's this uh uh it's not a club anyone wants to be a part of, which are, you know, incredible musicians and

artists who just seem to have this incredible uh talent and intensity and they die at 27.

And um you know and there of course certain things like music and art sometimes are you know there's overuse of substances and substances were almost

always involved in these various cases.

Jim Jim Morrison and Jimmyi Hendris and you know Janice Joplain and there are others. I don't know if they're all in

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

are others. But this idea that for people whose quote unquote flame burns really hot, their 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, it taps into the dopamine system, the epinephrine system. This is

definitely the stuff of energetic deployment and release and transformation. Like these are not drugs

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. Yeah. In a parallel

vein, um I once had a conversation with someone that I understood uh 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 went and started reading about child prodigies. You know, you don't meet many

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

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

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.

>> Mhm.

>> And we're 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. Mhm.

>> And then I'd like to talk about how the things that all of us can do can keep our m mitochondrial reservoir high enough so that we can allocate it in

different directions. But I'm just

different directions. But I'm just curious your thoughts about people who seem to their their fire burns really bright and then it goes out early and prodigies seem to

>> channel all their energy and do 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 a parallel in biology which is how different species develop much faster then they reach you know reproductive age much faster and then they die much earlier

>> much you know earlier like mice for example uh they live like two to three years and they develop really quickly >> um uh 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 uh 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, stem cells, 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,

right? an organism that develops, grows, and dies in like 80-ish years uh uh have very diff different developmental rates.

And then they ask what's different between that? What controls the pace of

between that? What controls the pace of development? And they found that uh the

development? And they found that uh the main driver of this and then they did experiments where you can accelerate or decelerate the pace of development by uh 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 and that was regulated by NAD. I think a few people who listen to

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 rate at which energy is transformed.

>> So interesting. I um long ago I I was getting frustrated because all the discussions in the longevity space were failing to acknowledge I'm a developmental neurobiologist. First,

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.

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 your lab could 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 at one stage and then it continues. how long the the acquisition

continues. how long the the acquisition of secondary sex characteristics carries on essentially is a measure of the duration of puberty because it reflects 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. They 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

this is. And he was very like muscular and lean and and he'd 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

is." And there's no there was no envy or upset about this. Um, you know, shouting for it or anything. I really like him as a person. I was like, "Well, he looks

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

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're

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. Uh 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

going through. And again, nothing in biology is free. That's kind of one of the basic energetic laws of life. You

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 uh 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

quickly. My son is six years old and he's learning so much changing all the time. Uh so energy expenditure is like

time. Uh 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 21ish it's adult and then it's a flatline for the rest of the of

adulthood. Then around like 70 years

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 keep our muscles and mo movement etc. breathing.

>> Yes.

>> Um exercise a lot of it is just breathing. Um as

breathing. Um as >> bringing oxygen to your mitochondria.

>> Well as a friend who's in incredible shape what once told me I said what's your workout regimen? He's in his 60s.

He's just in in 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

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." [laughter]

Former SEAL team guy. So, they're a little extreme, but you know, he makes a good point. But the idea is that that we

good point. But the idea is that that we understand from this paper published in science a few years ago that metabolism, basil metabolism doesn't change much as we age. We thought, "Oh, my metabolism

we age. We thought, "Oh, my metabolism slows." It's not true. Once you hit

slows." It's 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

all. I think as you pointed out, until one's 80s.

>> Yeah. It depends at what level you look at metabolism. If you look at the

at metabolism. If you look at the cellular level, they're >> I'm referring to the caloric basil caloric need, >> how much energy you you need you should consume to >> Yeah.

>> minus basil metabolic rate like minus your uh the running the lifting etc that you do. Now of course lifting can add

you do. Now of course lifting can add muscle which then raises your basil metabolic rate but >> just this idea that oh my metabolism is slowing as I age turns out to be completely false. People have used that

completely false. People have used that as an opportunity to write off they're overeating. They're over consuming

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 of aging, the BEC model. And so we could dive into

this. Um but I think there's significant

this. Um but I think there's significant changes that happen in some cells as cells age. They start to actually burn

cells age. They start to actually burn energy faster. When cells become

energy faster. When cells become scesscent, 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 cell, not all cells, some cells in the body, they're kind of over the edge. They're becoming scesscent.

the edge. They're becoming scesscent.

Uh, 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 cytoines. And when

those cytoines reach the brain, the brain says, "Oh [laughter] >> 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 if you 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.

And really what this is is you're bringing the organisms energy resistance, the the the cells that are struggling. You're kind of normalizing

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

in quotes. Uh >> we feel less energy.

>> We feel less energy. Thank you. As we

age is because of inflammation in the body. um calling more energy to be

body. um 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

energy. So by reducing inflammation, you have more energy to allocate to other things.

>> Correct.

>> Got it. And so this is very different than how we were talking about at the beginning when I said, you know, my adviser came up to me, why do we have less energy? I just imagine it was rund

less energy? I just imagine it was rund down 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

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

budget. Am I going to exercise more to get more more mitochondria so my brain and body have more energy? 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 6 to8 hours of sleep each night.

I've been pretty religious about that for a long time.

>> And try to not burn energy on drama or mind-numbing things. And certainly don't

mind-numbing things. And certainly don't use any substances that use up a lot of energy >> excessively. I do drink a lot of

>> 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. Modafanil, I've taken it once when sleepd deprived. You feel as

if you slept 8 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

later. It's the long-term effects of this. And I think this is why people who

this. And I think this is why people who use um empetamines and and cocaine and things like that, stimulants, we often find that sure they die of heart failure. That's very common actually in

failure. That's very common actually in people who use cocaine earlier. We talk

about this, but let's just be direct about it.

>> They're borrowing energy from the future is what you're doing. 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 as a a reframe

as well. Inflammation as a a reframe that to me completely changed my perspective on what inflammation is.

Inflammation is an energetic signal.

Mhm.

>> If you there are cytoines in your in your blood, it means somewhere in your body and that's not true of like all cytoines but the major cytoines that we think about like IL6 interlucan 6 it's

secreted by muscles not during the exercise like you're doing your run right like let's say you run intensely for an hour for two hours IL6 doesn't increase it's when you stop exercising

boom you get this beautiful spike of IL6 and then you ask where is what is that so IL6 is a cytoine right it's a a cellular signaling system. Uh, 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 you're 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 muscle's way of telling

energy. It's the muscle's way of telling the rest of the body, I'm running low on energy, right? Please help. And then it

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 v your vitality, your vigor at least for a little bit.

>> Uh and rest. And like you know Arnold said that 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 6 to 8 hours definitely uh and about stimulants like caffeine uh and other uh stimulants what they do is they prevent you from

feeling energetic stress. Mhm.

>> 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. Uh and

now they're clinical trials and which I think are are potentially dangerous that are happening where uh those drugs are being developed antibbody based uh 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, uh, and you know from you think the body is a molecular machine, you think here's what's happening when people are sick, they

have cancer, right? GDF-15, this growth differentiation factor 15, it's which is a protein, it's a cytoine. Uh, 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 it will start to secrete GDF-15.

So people with cancer uh who end up developing cexia right their muscles melt away they tend to have very high GDF-15 and then GDF-15 can go to the brain and the 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. Uh so what happens uh

including tumors. Uh so what happens uh 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 is GDF15 mean if you have a

lot of it in your blood. Well animals

actually puke and it cause you know an aversive reaction uh visceral malaise is is the the technical term. So you feel like GDF-15 which is produced by

cells struggling energetically anywhere in the body signal to the brain and makes you feel like We know now also GDF-15 is the trigger for morning

sickness uh in pregnancy. So the reason you know uh women especially um hyper emmesis 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 10,000fold there 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 um 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 Uh and so there's this one trial that was published in the New England journal uh last year and they show as

expected if you block GDF-15 with a monoconal antibbody u 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

right? And energetically, I suspect this is the right thing to do because you're saving 10 15% 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

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, at the fine print and you look at the table where they report mortality, mortality was double in people who were receiving the drug, the

trial was not the the powered to detect mortality as a primary outcome. It was,

you know, powered to detect changes in in body weight. Um so, um so that that didn't end up being a main finding. If

this is real, right, you're preventing people from losing weight and they feel a little less nauseous, but there are 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. 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 uh molecular uh channery 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 were going

to tell me that more of them lived you I mean twice as many died died and and there recently there's another trial uh large scale trial for heart failure uh that looked at this using this antibbody

to block because when the heart struggles dilated cardiammyopathy 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 about GDF-15 is a little different than what the rest of I think the the field thinks people see GDF 15 as a marker of

inflammation And then maybe that's like immune or I think it's it's a marker of energetic stress. The heart is calling out for

stress. The heart is calling out for help and trying to kind of calm down the rest of the system, right? By signaling

onto the brain.

>> Turns out uh many more people developed uh heart failure and like adverse events uh under the drug. So they stopped the trial >> where you block GD15.

>> Yes. So if you block the >> This is the danger of of of molecular thinking of everything in terms of receptors and and ligans like the things that plug in. People might not know what ligans are things that plug into

receptors and activate them. I mean, I love modern biology. There's a lot of beautiful things, but but the it the systemic effects are hard are impossible to predict. I guess that's why you run

to predict. I guess that's why you run these trials.

>> I do have a question as it relates to this uh which is a big theme of your work, which is about stress.

>> Uh well, I'm sure people are wondering by now, tell us about the gray hair reversal. So, let's start with that.

reversal. So, let's start with that.

Let's just get that out of our systems. I will say um uh despite some some theories, not that anyone cares that much. I've never dyed my the hair on my

much. I've never dyed my the hair on my head, I do have some grays, but the the number of them waxes and waines with how 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, >> correct?

>> Um but I don't dye either my hair or my beard, so I'm a I'm a I'm a natural experiment in this. Yeah.

>> Um, what's the deal? Can people reverse the graying of their hair by reducing their stress? Can people accelerate the

their stress? Can people accelerate the graying of their hair by stressing more?

>> Mhm. Uh, 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

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 a hallmark of aging which is you know depigmentation losing color in your beard and your hair um is something that happens to almost everyone but at different you know stages of life and

and so on and then on the same person and the reason we got into this was that uh 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. Uh but yet some hairs go

stress levels. Uh but yet some hairs go gray when you're like late 30s and then some hairs go gray when you're like in your 80s. What the hell's happening?

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% of how long you live that genetically driven. Like the best studies put this at around 7%. 7% of of

longevity is genetically inherited maybe and then about 90% is not >> is lifestyle factors.

>> Lifestyle, you know, food exposures like whatever whatever is non- genetic.

>> People will take solace in those numbers.

>> Yeah. I I think those are are really powerful numbers. Uh and they surprise

powerful numbers. Uh and they surprise me because I 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

is legacy. It's like dogma. Uh it's not science-based. It's dogma from, you

science-based. It's dogma from, you know, the the human genome project era.

Like through the '9s, 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

2001. And then there was like 10 20 years of G-W was genomewide 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

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 a it was a useful hypothesis like many hypothesis are. It led us to, you know,

hypothesis are. It led us to, you know, learn a bunch and the human genome, the sequencing that was such a a such a a driver of progress in in 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 conneto, uh proteomes inflamm but not sufficient.

>> Correct. We want and need the information, but it's not sufficient to demonstrate anything except it's a hypothesis generating experiment. Yeah,

>> I I know this cuz I sat sat on grant panels for a long time and you look at these incredible studies like we're going to measure the difference between this cancer cell and that cancer cell

and this and it's great, but the information you get is necessary, but it's it's not conclusive of 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. Uh but I think in general academic science has kind of lost track with its core purpose. Uh and now we have like an

purpose. Uh and now we have like an incentive system and there's a lot of forces at play in administrative you know processes that don't serve the the primary end goal which is

>> well it's all getting revised now. So

[laughter] it's uh for for better or worse it's all getting revised. So I see your point.

getting revised. So I see your point.

I'm I'm um uh 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

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

interesting. So um >> that it's re 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 a piece of of a

>> right? So you have a 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

like it's it's a bit like tree rings, right? If you cut down a tree and you

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

right? And then 45 years ago there was a drought and you the tree rings look different." And so there's information

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.

relationship. Yeah.

>> So if and hair is grow >> writing a grant after the grant. Yeah.

[laughter] >> That was actually part of the data for that that study. I was one of the participants early on because we became interested in this. We found hair that were two colored 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 and 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 uh and then uh 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 aging hair graying is is there's plasticity

here. And then we found hairs where the

here. And then we found hairs where the the hair was white and it went back to being dark. And

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. She had like really dark hair

beautiful. She had like really dark hair and then the root was dark and then there was a segment 2 centimeters about like almost an inch of of white and then the rest of the hair was dark again.

>> What happened in that 2 centimeters? Did

she exactly? So that became the the the question. So then we developed we said,

question. So then we developed we said, "Okay, we need to do this quantity."

>> She didn't tell you what had happened.

>> No, no, no. She we were collecting hairs in Ziploc bags. So now people started to mail us, you know, ziplockc bags with hair. Um uh and we got some hairs from

hair. Um uh and we got some hairs from France, hairs from from Canada, from different places in the US, across body regions in South Asian,

African-American, you know, uh uh white.

Uh so it 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. Uh so then we can

get like uh 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 lo it 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 I sat down with this participant and then said, "Okay, this is now uh and this is a year ago." Uh, and then you can look at your

ago." Uh, and then you can look at your calendar. What was the most stressful

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 rate this there. The yaxis is most stressful

this there. The yaxis is most stressful at the top, least stressful, zero at at the bottom. And then they they put

the bottom. And then they they put points and then connect the dots, right, with a 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 [laughter] 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 submitted my thesis she just graduated her PhD uh on the at Stanford actually and then uh she uh you know had a chill

uh 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

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,

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 it mapped surprisingly perfectly with the with the the graying, right, where the hair lost color. So it was the hair the the stress

color. So it was the hair the the stress peaked for two months and then came back down. She said this these were the most

down. She said this these were the most stressful two months of my life.

>> Super interesting. Um and the the papers got a lot of press as it as as it should be. I've received about 300 emails since

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.

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 [laughter] and that 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

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.

>> Mhm.

>> Aka stress. A different kind of stress, not psychological stress.

>> Yeah. Maybe it depends how we define stress. We define stress as anything

stress. We define stress as anything that costs energy.

>> Well, inflammation costs energy.

>> Inflammation costs energy. And making a cytoine costs energy. And if you're a cell and you have a receptor for a cytoine and the cytoine dogs, the lian

dogs, that's going to cause 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. Have a perfect situation for

very low. Have a perfect situation for development. As we get older, we

development. As we get older, we generally move a bit less or a lot less.

>> Or a lot less. Yes. But ideally, it's just a bit less or maybe we move more.

And in general, people need to eat less.

>> Mhm.

>> Not more as as a rule.

>> Uh, 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

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 grays hairs >> and reducing stress ungraes hairs.

>> It's It's a correlation.

>> It's a really It's It's a correlation, but it's a really cool result. I want to talk about restoration and recovery of energy maybe with the the hair graying.

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 cho chopped it into pieces and did proteomics.

>> You have to because you're a molecular biologist, [laughter] right? And I mean mitochondria is our way to tap into you know the biology of energy.

>> So then we we we thought maybe there's something there. And initially I didn't

something there. And initially I didn't think there were mitochondria in the hair. Turns out every hair that we walk

hair. Turns out every hair that we walk around with is loaded with mitochondrial DNA. And you know forensic if you find a

DNA. And you know forensic if you find a hair on a crime scene you can figure out who was there. The DNA that gets sequenced is not the nuclear genome.

It's a mitochondrial genome >> really. Uh, and because hairs have a

>> really. Uh, and because hairs have a very high concentration of mitochondrial DNA.

>> See guys, you can't commit a crime expect to get away with it because if you leave one hair, Martin's lab is going to >> We don't sequence it.

>> We don't do forensics. You don't. 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

proteins. And I would I did not expect that. And we repeated those experiments

that. And we repeated those experiments in two different proteomics core. You

know that there's uh the and the proteomic score 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. Uh but we were able to kind of get good resolution data for other non-caratin non-hair proteins and three mitochondrial proteins were

consistently upregulated. there was more

consistently upregulated. there was more of the mitochondrial energy transformation machinery in the the gray hair compared to 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.

Inflammation associated with aging is an energy requirement. Being sick

energy requirement. Being sick >> creates different energy requirements and we need to obey these different energy requirements. Fascinating.

energy requirements. Fascinating.

>> Yeah.

>> So, in terms of removing or reducing metabolic demand in order to keep our system going, >> uh, first of course is sleep, >> right?

>> Uh, you were telling me earlier before we started recording that during sleep, how much does our metabolic uh, 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 uh that uh allows us to go um

you know to to stay alive with 10 15% lower energy expenditure and that they're different between different people but you know 10 15% is kind of a an average of how much energy you're

saving by sleeping and that there's a theory of why why do you know every why does every animal need to sleep and if you sleep deprive of a mouse or rat or

you know an animal they die eventually and we know from like severe cases of of mania and you know bipolar disease people can die from from going without

sleep for you know multiple days. Uh um

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 torper right almost like h

meaning hiber hibernation uh then you somehow the the organism can't sustain that and I we have some thoughts as to why this is >> I was reading recently about this glimpmphatic clearance of waste in the

brain that occurs during sleep and uh 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 pandas sleeping on

their side. The giraffe apparently puts

their side. The giraffe apparently puts the top of its head down uh 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, fallen asleep like that a bit. But in general, sleep is a time

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

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. No, you can't eat more to get

>> either. No, you can't eat more to get more energy.

>> That's very clear. Yeah, that's a very important statement. Um,

important statement. Um, now I'm long been curious about things that people can do in order to either reduce their sleep need or in 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 8 hour need to a 6-h hour

need with a 40minute investment of meditation. What are the data on how

meditation. What are the data on how meditation reduces u 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

mitochondria sleep. You lose consciousness and the body you know goes into this hypom metabolic restorative state and yes there's glimpmphatics 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 just finished an experiment

>> right? So we just finished an experiment uh where we had people come in the lab for 24 hours, sleep into the lab and Evan Chosen, 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 hypomabolic state and you're kind of conserving energy. How is

energy reallocated? So we see sleep as a two uh 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,

energy. Every time the heart contracts, right, cy dasily, 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

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

in time. One is vital. You need to keep your heart beating. It's 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 costs energy and then your blood pressure increases that cost

energy. Heart rate increases cost

energy. Heart rate increases cost energy. You're sweating a little bit

energy. You're sweating a little bit cost energy. Your hair rises you know

cost energy. Your hair rises you know anything that you're you're doing will cost energy and then steal that energy we think from a third bucket which is what we call growth maintenance and

repair GMR. uh 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 the a cell. If the cell has you needs to repair its membrane, needs

to repair its DNA. This would be growth, maintenance, and repairing. If you make new more mitochondria, mitochondrial biogenesis after workout, that would be growth, maintenance, and repair. Uh and

because there's a finite energy budget, there's an economy of energy that how much energy you have needs to be distributed between those vital costs, the stress costs and the GMR, growth,

maintenance, repair cost. 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. Uh and what sleep might

learning maybe. Uh and what sleep might do is actually shut down all of those stress processes. When you sleep, heart

stress processes. When you sleep, heart rate variability increases, right?

Parasympathetic tone increases.

Sympathetic nervous system goes very quiet. Uh and then all of the the stress

quiet. Uh and then all of the 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

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%.

>> Wow.

>> So 10 to 15% we said earlier that's how much you can save energy by just sleeping. Uh meditating it seems and in

sleeping. Uh meditating it seems and in some uh trained people can bring energy expenditure down by 40%. This is more than sleep. So they're able to shut down

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 and meditators u and then maybe that energy can be reallocated to growth maintenance and repair. So if you do more of GMR

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 um um

self-related thoughts, [laughter] uh then maybe you're you 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

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.

>> Mhm.

>> Or I coined a variation on it non-sleep deep rest. Uh you it essentially

deep rest. Uh you it essentially consists of lying down >> intentionally staying awake and uh 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

physical energy. your vigor is restored even on less sleep.

>> The other is that it doesn't impede >> your ability to sleep at night. If

anything, it facilitates it. Whereas

naps can often uh create a sleep inertia. You feel sleepy afterwards.

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 nijra is very very efficient

this way. The other thing is that I've

this way. The other thing is that I've been playing with lately um that I found to be tremendously useful. I sort of joke about this. I was telling my girlfriend the other day like um

we'll just 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 noticed 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 sleeps 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 um this idea of not just lowering the lights, dimming the lights, but also um 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-leep activities being very relaxing. We hear that for the

very relaxing. We hear that for the d-stress component. Yeah,

d-stress component. Yeah, >> but I suspect that the brain is already going into a sleeplike state.

>> Yeah. So I suspect that's accurate. And

um if you're by, you know, um creating that environment and then it allows you to relax, right?

What relaxing means basically is you you decrease the energetic cost of of sustaining your organism. Uh then

lowering heart rate, you know, lowering cortisol in your blood, norepinephrine, you know, catakolamines and the things that cost a lot of energy. Uh we've done experiments in cells in a dish. you give

cells uh gluccocorticoids like a cortisol mimedic or norepinephrine >> and then we wanted 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 the those cells go into like uh a whole choreographed

respon evolutionary you know ingrained response that prepares them for the future right it's called alostostasis uh and that cost a bunch of energy And we found it was about 60%. So the the this

doesn't happen you know in human beings but if your energetic metabolic rate increased by 60% >> right with gluccocorticals you'd be in big trouble. So it might not be as much

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

stuff. So if you can decrease the level of those hormones and decrease a level of cytoines in your blood inflammation uh 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 whose sleep energy expenditure you know drops significantly like 20%. Other people doesn't does

like 20%. Other people doesn't does doesn't drop you know almost at all. Uh

in particular people whose mitochondria don't work very well. Uh so we've been so fortunate to work with patients and uh in the I'm not a physician but uh I'm in the clinic half day a week to and I

see patients that I've followed now for about six years who have genetic mitochondrial diseases. So they're

mitochondrial diseases. So they're they're pretty rare but 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 fat you know they don't feel well. They avoid

exercise at all cost 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. GDF-15 through the roof.

uncomfortable. GDF-15 through the roof.

>> Uh the best biioarker of mitochondrial disease is actually GDF-15 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 GDF-15 as a signal. uh

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 uh 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. Uh so that that positions mitochondria in in the context of restoration and you know the our ability to heal and uh and

the and lifespan in those people is 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, um we should talk about nutrition

and exercise and supplements, dare I say, >> um and prescription drugs, >> um including the GLPS.

>> So, I realize you're not a nutrition expert but >> you think about energy. Uh you can't out eat a bad night's sleep. Uh but we all need nutrition. It when you personally

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 oneizefitall 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 uh people feel really strongly about. Uh,

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 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

never had. I've met several people now who've had this kind of lifechanging uh energetic shift happen when they go on a ketogenic diet and when they in store, you know, intermittent fasting.

Life-changing Mhm.

>> So they know that that that this is real, right? And um and then you do an

real, right? And um and then you do an RCT and [laughter] and then you say, "Okay, let's test the randomized control trial."

trial." >> Yeah. Thank you. You do a randomized uh

>> Yeah. Thank you. You do a randomized uh clinical trial and then what you do there is you feed everyone the same thing, ketogenic diet or standard 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

right outcome. And then you have like let's say 50 people here, 50 people here. And then you ask, did the

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

bit, right? And then if this the study was adequately powered and there's like an 8% you know shift in your primary outcome then it becomes p less than 0.05

the the p value the statistically the statistical uh you know value here becomes significant and now you say the ketogenic diet is effective for this or

the ketogenic diet does not work you know for for eggs. 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. Uh and then there are

changed truly. Uh and then there are people who didn't change anything. And

then there are also people who got worse. Uh and then you average everyone.

worse. Uh 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.

Like no, nobody is actually the average.

>> Literally.

>> Literally.

>> And and then uh the ketogenic diet could literally save lives and it could cure or be like a really solid treatment for

schizophrenia or bipolar or or Crohn's disease or whatever it is uh 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 this. It's the

only solution.

>> Yeah. And and that you there's a clash here between the value of the human experience, right? You know that this

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

your potential. And then you see the science that, you know, the capital S science that tells you no, what you think works doesn't work. And then no, but it works for me. And then you have a

white coatwearing person who says no no no I have the authority I can tell you this RCT shows that it it's not effective and I think this really is damaging like this it makes me angry I'm

I'm I feel uncomfortable when I talk about this because this is completely disregarding the human experience uh you know and in service of this you know framework that doesn't serve the

individual those the RCT was invented for very good reasons and and it it was it's very useful in some circumstances like do antibiotics work? Uh should you you know be do doing surgery this way or

that way? But when you get to

that way? But when you get to interventions or treatments that are likely to have 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, this 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 um 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

um not excessive not caloric calorically excessive. Yeah. So eating too much for

excessive. Yeah. So eating too much for sure damages the whole system uh including mitochondria. Um so the the

including mitochondria. Um so the 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 that work for different people. So

we're working on uh a platform that would empower people to get some objective readout right of energetically how are they doing and then and then

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 uh that rushes through your body with different levels of resistance then you can uh think about the food you put in your body is actually fueling that flow right like you are the

movement of energy and that is continuously uh fueled by you know what you put in there uh and then the uh by the activity you do and the the kind of

things you engage with. Uh so yes we need a framework for this. We're working

on that. Uh, so that's the individualized piece, right? There's

very at this point I'm pretty convinced there's no one diet that is a best diet for everyone. I've seen people thrive on

for everyone. I've seen people thrive on very different diets. uh since we've been kind of working on related areas and um and a few years ago I received a

research prize the Bazooki prize in science uh which was so enabling and Bazooki group is a family foundation uh whose 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 um uh they came across a a psychiatrist who was using the ketogenic diet as as a treatment. And so he went

on a ketogenic diet and uh Jan Bazooki the um um the mom um said like I had my son back like within a few weeks he his

mood you know got stabilized. he was

able to sleep and uh he stopped kind of you know cycling between mania and and major m depression. Um so for him like

you know that really worked and uh so I was sensitized to that area of of of work and research and then dozens of other patients and I've met you know so

many people now who who manage their mental health disorder with uh ketogenic diet and they they test you know their blood ketones to make sure they're still in 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?

>> Uh, 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 it

puts the organism in this prohealing state, right? which is probably why you

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,

something. Uh and then I had much more, you know, better clarity of mind. Uh and

that's what a lot of patients report as well. Like,

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. Uh there there's good research.

When I saw that study, like, oh my god, this might be why, you know, I feel like 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,

intolerant. Uh and and then you know, you can make all sorts of theories about maybe it's like the detoxification enzyme and their liver like energetically they're 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

right? It's a toxin. So everything in biology costs energy. Nothing is free. A

basic [snorts] energetic law of life. Uh

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

sleep. The data came out recently. This

was covered in the uh traditional press.

Uh I think you can look it up folks.

It's a there's something like a 50% reduction in alcohol uh consumption in the United States now. I think it's the lowest alcohol consumption in something

like 90 years. It's pretty spectacular.

We did an episode about alcohol a couple of years ago. It turned out to be a very popular episode.

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 or before you start to run into some issues um 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 Humphre 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

now. The the way those studies were designed was was poor experimental design. All of it speaks to the fact

design. All of it speaks to the fact that zero is better than any.

>> 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

meetings. I would uh take solace in the fact that a I'm going to sleep relatively early. 11:00 isn't that

relatively early. 11:00 isn't that early. But I didn't stay out late and I

early. 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 at bigger labs and I was like I'm going to take your lunch. [laughter] I'm going to

take your lunch.

Yeah. I'm Yeah. That and I'd recommend that they watch certain Netflix serieses because that'll definitely take your competition out. No, I I would watch

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 uh steals a piece of your energy budget. So whether you want to,

energy budget. So whether you want to, you know, allocate that energy, if you have extra energy to spare, you want to do that. Uh but

do that. Uh but >> that's a good way to think about it. In

some cases uh let's say you know uh vital processes nothing you can do about this and as you age probably those increases stress processes >> right the mind creates most of those at

a 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

we from our past that we deal with u if if this is burning a big chunk of your energy budget right every Hey, 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% of your energy budget and when you drink alcohol that 30% goes to 5%. Right?

>> Uh you're you're maybe wasting let's say 10% of your budget to detoxifying alcohol. But if you're relieving that

alcohol. But if you're relieving that stress, you know, I suspect this is why um you know, there are people, you know, that really like their social drinking

because it relieves kind of a a stress uh 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 as a key thing to think about and then how we

allocate energy at the mitochondrial level, but at the decision-m 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

energy expending. Although we can't take it so far that we're not getting enough sleep. I mean, you know, there's

sleep. I mean, you know, there's [clears throat] always the the housekeeping that needs to be done of of sleep and nutrition, etc. I am curious about exercise.

>> You mentioned training for a marathon will double the number of mitochondria >> at most. Yes.

>> 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

efficiency? Um, but not so much that you're robbing mitochondria from other areas of your of your biology that are critical.

>> Uhhuh. Yeah, a good question. Like if

you exercise too much and you're a healthy a young healthy male, you can actually decrease testosterone level, right? Like endurance training can shut

right? Like endurance training can shut down your testosterone production, your your reproductive system basically.

>> Uh so that there that trade-offs the the kind of trade-offs we talked about with uh you know young females also applies to to males and and those kind of ways.

um where that threshold is I think is also highly individualized and um 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 there's a limit and I used to be a competitive cyclist and I I race kind of semi-professionally and in my college days and uh and I knew that if I worked

out if I you know was on the road and I used to do like intense and long distance workouts if I was like I I logged all of my training, you know, how many hours, kilometers, all of this. Uh

if I did more than like 20 22 hours a week on the bike, I would get like Achilles tendon that was kind of my sweet spot um or my sensitive, you know,

weak spot or or my knee. Um 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

cyclist. I I wanted to at some point maybe I'll 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 uh sprint uh building exercises and I weighed like 10 15 more pounds than I 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 amount of great amount

of food. And so the the trade-offs at

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

activities. And that sweet spot, I think, is unique to each person. Uh, 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. Uh,

running. Some people use gambling. Uh,

you know, whatever it is for you. Um, so

I don't know that there's kind of a number of hours, number of miles per week, for sure not. Uh, and whether you do something, you know, that inspires you or whether you do something and it's it's a it's a 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 spent a lot of time in the in the gym, uh, Steven Presfield, who you know, you 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. uh too much resistance

true mentally. uh too much resistance crushes you, right? And then it's like too difficult and and it's demoralizing and and deenergizing. But not enough resistance is is not inspiring like and

and then being bored like being imprisoned. That might be why, you know,

imprisoned. That might be why, you know, being in prison is so such a a it's a thing we do to people that who've done really bad things because it is it really crushes a human spirit when they

have nothing to do. And having something to do is a bit is kind of exerting resistance to the human mind. So having

to I 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

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 actually controlling energy flow >> transforming >> transforming it um 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

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

turning on. Your brain doesn't change if it if it's in a state like any other state. This is unfortunately why

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 is happening now is really

important and it actually grabs too much. And that's PTSD. It it grabs

much. And that's PTSD. It it grabs random events. It's it's a whole thing.

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,

resistance. If you can do the thing, your brain won't change. If you can do the thing, your body won't change. And I

try and explain this in the context of of cognitive stuff, that agitation and frustration. Like you have to seek that

frustration. Like you have to seek that out. You don't want to overdo it. But I

out. You don't want to overdo it. But I

think if I wish they had told me that when I was in school, 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 your circuits are are primed to change.

>> Yeah. Anyway, I get very impassionate about so because it's how we get better.

And I think most people feel that they actually errors signal that more and tell your brain you have to change.

>> Yeah. Just it's just that the change takes time >> and it it takes 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 rel changing relationships uh any kind of transition by definition a transition requires change

>> which requires energy >> and I suspect the reason why uh life transitions are difficult is because they cost energy and we have a finite

amount of it. Um, so resistance, the energy resistance principle is something that we've developed recently with neuros uh that encapsulates this.

It says like life is resistance. You

cannot have life if there's no resistance. There's no transformation.

resistance. There's no transformation.

>> You're like a cadaavver.

>> Yes. Exactly. Or you're like a beaming, you know, light ray in outer space.

>> Yeah. It just goes on.

>> It just goes on, goes on. Never

transformed. You know, there's a potential for change, but it's there's no transformation. It's never going to

no transformation. It's never going to change until it hits resistance. A green

leaf on earth for example.

>> I love it. It's it's such an important concept.

>> And just to I think you think about bodybuilding and you know working out that how the body gets stronger. The way

the body gets stronger is by facing resistance, right? If your muscles get

resistance, right? If your muscles get accustomed to a certain weight, if you want to grow in strength or in mass, you need to go heavier, right? And so it's increasing resistance. Same thing if you

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 onto onto earth uh 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 in orbit and then there's nothing.

You're resisting the structure of your body.

>> They age very fast.

>> Yeah. Exactly. Astronauts don't

farewell. Now they have ways to compensate for this.

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where you can access a free 30-day trial. Again, that's

trial. Again, that's wakingup.com/huberman

wakingup.com/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. Um, co-enzyme Q10 a number

huge space. Um, co-enzyme Q10 a number of people including me take. Um, this

isn't a plug for it. It's just I take it. I was told that can help my

it. I was told that can help my mitochondria. Um, I don't take methylene

mitochondria. Um, I don't take methylene blue. It I'll mention why in a moment.

blue. It I'll mention why in a moment.

Uh, there are some peptides like SS31 is very becoming very popular now.

Cocktails of NAD, SS31, things like this. People are in Oh, yeah. People are injecting this stuff

yeah. People are injecting this stuff like crazy. Oh, yeah.

like crazy. Oh, yeah.

>> SS31.

>> I guarantee within a radius of one one mile, there are a lot of SS31 injected.

We're in Los Angeles, so Oh, yeah. SS31

um in cocktail with NAD it's very common there's uh there are a couple others um slooh slu there's another one all of this is um MC uh a lot of people are

injecting these peptides in effort to improve their mitochondrial function would love your thoughts on this don't worry you're protected no matter what direction you you answer [laughter]

>> 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 they make hormones and they make signals and but to your point about

supplements you I was a student when SS31 was discovered and I remember the the person who discovered Hazel Setto uh who discovered SS31 she was presenting at meetings and and so I've seen the now

it was commercialized is you know stealth peptide and then it went on the publicly traded. So um it's not lived up

publicly traded. So um 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

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 the

you know the metabolic circuitry that we have for flowing electrons to oxygen. Uh

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

feels terrible. It feels like if you hold your breath and you're you feel like you're going to 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 apart >> ADHD is another good example of that >> 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 uh but I I think that's um a fairly wellsupported idea >> uh and supplements in cases when your

circuitry is, you know, impaired. Uh,

like if you're deficient in in cozy Q10, if you take it, you're going to feel it.

Uh, and if you're deficient in something like vitamin B12, there are many parts of mitochondria that require uh B vitamins to to flow electrons towards

oxygen. So vitamin B deficiency

oxygen. So vitamin B deficiency different vitamin B's including NAD right is uh can really be terrible and people have chronic fatigue like

syndromes from vitamin B12 deficiency for example uh so in cases of uh where where there's a deficiency or you think there might be a deficiency uh maybe

supplements can can help you know paliate those uh my sense is you know we've evolved over very long periods of time and we're really well optimized

uh 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 uh 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 uh without supplements and and without uh you know medical intervention so I there there's a path uh to get there and so I

think there's there's a place for supplements but I've never taken a supplement and um >> and you have plenty of energy.

>> I [laughter] I cultivate my energy in different ways >> and and I I feel like it's um 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 know, help pharmaceutical companies or or other, you know, supplement type um to test the effects of supplements on mitochondria.

If we go in that route, then I 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

point. But I feel like my energy, my contribution as a as a scientist is better positioned and understanding the energetic basis of mind subjective experiences body and uh 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 uh, 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 cuz they had taken it recently. But um there are some data that um point to the fact that methylene blue can um intercolate

into DNA and possibly cause some mutations there. That worries me. Um and

mutations there. That worries me. Um and

there are some data as well and um Chris Master John talked about this recently um that if people are mitochondrial damage deficient, 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

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

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, as you said, the experiential aspects, meditation, uh,

meaning, uh, purpose, and this notion of flow is something that I want to just ask you about. Um, when you see things like Tai Chi, >> if you're in New York City, you see people early in the morning, if you get

up, you see them doing Tai Chi. Or, uh,

years ago, I saw an interview with Iggy Pop. Um, you know, as a, you gosh, like

Pop. Um, you know, as a, you gosh, 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

secret?" They always ask these kind of like, "What do you eat?" kind of things.

And and he was like, "It's all in the Chiang breathing." And it was and I

Chiang breathing." And it was and I chuckled because Tai Chi, Chiong breathing, I personally believe that whether or not it's running, Tai Chi, Chiong breathing or lifting weights, the

the activity itself has certain benefits related to respiration, blood flow, muscle stress, etc. in recovery, but that the additional layer of 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. Yes. 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

going to >> not brace myself too much. I'm going to try and quote unquote flow through it, >> but I'm also going to 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 metalarning >> that comes from just having done it over and over. So you you have this

and over. So you you have this expectation and understanding. You're

learning how to allocate energy. And I

would just like your thoughts about this. So I don't think it's Chiang per

this. So I don't think it's Chiang per se, >> Mhm.

>> Tai Chi per se, yoga, Pilates per se, lifting weights per se. I think those have each different benefits.

>> Y >> but what are your thoughts about learning to be a better Oh gosh, this sounds super woo, but what the heck >> energy channeler? [laughter]

>> Two scientists talking about energy channeling. Uh well this is not woo I

channeling. Uh well this is not woo I mean there the mitochondria flow energy you can say they their 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 of energy um is there like a molecular reality to chiong or toqi or

to you know prana or right like maybe um and maybe and if we look at all of these practices right and And then we ask what's the point of consilian 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 the states of consciousness states of mind that that we know are real uh like crazy states of consciousness that we can experience with psychedelics for example like what

can uh 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 understand or the our anatomy human anatomy you can understand as a an energy delivery 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

information. Uh instead of electricity flowing through, we flow food and then oxygen is at the other end pulling on electrons. Uh so maybe all those

electrons. Uh so maybe all those practices uh 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

measure this. We can't you know image this with an MRI. Maybe not yet. Uh but

I suspect there's a truth there and uh 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 going to injure yourself and you're not going to get as strong. You're not going to you know

strong. You're not going to you know grow or you know evolve. Um mentally we need resistance and there's like so 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 if the problem is too hard or you're too severe you you're going to

crush them right you kill their their their spirit. But if you don't apply any

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

never learn. there needs to be like just the sweet spot, right? That's what great masters, great mentors are able to do. I

think I I've 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

energetic processes. You know, they're transforming energy. They need the right

transforming energy. They need the right amount of resistance and, you know, not too much. And it it brings me more

too much. And it it brings me more compassion maybe for them as as energetic movements. And then I realize

energetic movements. And then I realize I'm more sensitive to the effect I have uh, you know, on them. But all of this movement and the Taichi, the exercise, you know, lifting and and resting is

analogous to what the heart does. The

way that the the the heart works is by contracting cy, right? And then by relaxing >> and then contracting and relaxing. Same

thing for like the way neurons work.

Boom action potential, refractory phase.

You need to have that period of science, right? Boom action potential and and

right? Boom action potential and and refractory. Same thing with sleepwake

refractory. Same thing with sleepwake cycles. You need to get awake. Your body

cycles. You need to get awake. Your body

temperature rises. Cortisol spikes up.

You, you know, you're aware of the world. You're exposed to stressors. Uh

world. You're exposed to stressors. Uh

if there's not enough stressors, challenges slash meaningful things in your life. You get bored and you want to

your life. You get bored and you want to die. So you need that. But then you need

die. So you need that. But then you need to kind of let go and and sleep, right?

So sleepwake cycle, same thing. And

maybe all of this has evolved from, you know, our existence on this planet.

Like the sun rises, things get warm, right? And there's energy flowing around

right? And there's energy flowing around and then the sun sets. It's same

movement as sunrise, sunset, you know, day, night is contraction, you know, resting yoga. The the whole, you know,

resting yoga. The the whole, you know, practice of yoga is based around this.

Like you strain your muscles a great poor 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 ready the body by

shavasana. So you you 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 uh [laughter] which uh because if if we do too much doing I think you know many professionals know this if you're always in a 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 it's healing the body um and consolidating memories and you 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 uh clearly what I'm hearing and uh 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 the challenge that we get pulled into >> the drama or the numbing out of some online activity or the uh you know the

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.

>> Um, 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

through. So and and I think if >> if clearly people learned a ton today, but if nothing else they they now understand the biohysical principle that it's through that resistance that you

direct and create energy for something else.

>> Transform.

>> You transform. Exactly. Thank you.

>> Good managers know this 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 uh and and the way that

learn. Um and uh and and the way that happens is by creating the right amount of resistance. And uh uh Stephen

of resistance. And uh uh Stephen Presfield said this uh the first time I heard of him, he was on the Joe Rogan 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. Uh and he talked about how uh

energy. Uh and he talked about how uh when you feel afraid of something, right? like as an artist, I think he

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 and you're

like oh like I don't know like this is scary 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.

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 uh I can think rationally and think logically about steps in a biochemical pathway and about like

logically like in five years and 10 years like doing strategic planning. Uh

but I I I have an increasing um sense that uh 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 woo like I I like this or like this is a little scary right um I started to ask my wife you know uh and she's really good at this how do you

feel I I think I used to ask my partner uh 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 the space for that person to really answer from that place then you actually get to you know

uh tune in to their energetic state and then you can be I think much better partner if you see a relationship as an energetic u um exchange right and then

uh and then I can be a better I I can be in a better state if I know that oo she's not feeling Great. And and then I think we've um I think the more you cultivate this kind of energetic

awareness, I agree awareness, personal awareness, and I would say energetic awareness. Uh

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

beings. And and that's not a new concept. It's I think the foundation

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

self. And then you realize at some point there's no self. I'm this 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 uh I'm not sure how it all you know fully gels together but uh 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 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 um and so without self-awareness, I think we're not always doing you fulfilling our potential. And

fulfilling our 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

present. And when you're present to someone, it's basically saying, I see you energetic process and I'm opening to you. Uh you know, how are you feeling?

you. Uh 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

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.

>> Uh 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 uh 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 uh uh

intellectual you know cog um social all of those I think probably boil down to is is this thing helping energy flow through my mitochondria more easily or

is it bringing me a resistance >> uh 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 and I learned.

>> I love it. It's a mitochondrial uh or energy flow ccentric view of of everything and I think it 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 uh at some point. I'm only half kidding. uh

some point. I'm only half kidding. uh

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. It's it's not it's not as

take effort. 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 uh

solutions, uh 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&A. So, um 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

short answers. First question is why is it that over consuming calories causes disruption to the mitochondrial pathways?

>> Yeah, 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 [snorts] up the voltage, right? Right? So you're like pushing

right? Right? So you're 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 evolve to be

mitochondria. Mitochondria evolve to be super sensitive and then when there's like a bit not enough energy they change our behavior. If there's too much energy

our behavior. If there's too much energy they change their behavior there chronically too much energy pushing on them. If you do the we have a little

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 the voltage equivalent uh 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 loss like too much reactive oxygen species and too much you know the damage

molecular damage can happen. That's

probably why overeating and why diabetes and why uh you know metabolic diseases increases the rate of aging and increases the rate of all sorts of the different diseases. I think it all

different diseases. I think it 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 andor measurement. Mhm.

So the measurement piece, we're working on this. The Anna Monzo uh in our group

on this. The Anna Monzo uh in our group uh 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 and you want to explore the the molecular differences between mitochondria and different organs of the body, you can go to mitoypeexplorer.org

or uh and then explore the different mitochondria and different organs. uh

tissue organ specific mitochondrial optimization uh I think mostly is going to be driven by the the organ or tissue specific use and and you know flow of energy in that

tissue like we were talking about earlier if you train on something you train you know on playing the violin you're going to parts of your brain are going to be you know more activated

specific circuits are going to be um uh activated together they're going to you know wire together and and then you make more mitochondria most likely and and you know probably become more efficient

as well. So there's rewiring at that

as well. So there's rewiring at that level. Um so the I think it mitochondria

level. Um so the I think it mitochondria follow or are there to to serve the flow of energy. Uh so if you flow more energy

of energy. Uh 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 as little you know channels to flow energy

towards oxygen. uh so yeah I don't know

towards oxygen. uh so yeah I don't know that we have ways yet maybe with uh you know light therapy uh photobiomodulation or maybe electromagnetic field at some

point uh we need to be developing as you know healing science uh unfolds and we understand ourselves energetically uh I think we need energy based or

energy informed approaches to uh help organisms heal and and probably those are going to target mitochondria >> yeah using [clears throat] 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.

>> Yeah, 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 uh advanced meditators can increase blood flow in like one uh part of the brain and uh so there there might be

unsuspected ways of tapping into um you know using the mind basically to direct energy in different ways. I I've started to uh see the mind as you know a master

regulator controller of 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 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

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 a you know

with my >> physician. Are there any companies that

>> 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 uh you know companies that have popped up because like this is a future like thinking ourselves thinking about ourselves energetically realizing we are energy then 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 science of energy mitochondrial biology and

psychobiology with the human experience uh that really is what moves us into into into action and determines whether you know our lives is is worth living.

Those things haven't been brought together and and we haven't also explored scientifically the healing process. So we're developing an

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

health. I don't know now of things that I I would use to tap into the the health of our mitochondria.

>> I can attest to both the pro- mitochondrial health and antimitochondrial 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

recommendations. There are a lot of busy people in this question list. They're

saying, "I've got kids. you got a busy job.

One, two, or three things that are straightforward outside the typical, you know, exercise, get your sleep, etc. 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

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 uh and I think it's hurting him his health in his like now in his 60s. Um 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

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. Maybe it

happens inside the body and then you get rid of the bad mitochondria. You make

more new ones that work better, more more efficient. So being hungry once in

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. [laughter]

hour. [laughter] >> Uh finding ways to be out of breath.

That can be like a run. It can be being at the gym. Uh you know, whatever makes you breathe harder. You breathe harder because your mitochondria are calling for oxygen. It's it's it's that simple.

for oxygen. It's 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 I I need to say something about meditation. I think somehow

about meditation. I think somehow meditation does something to our energy that is uh valuable and just yesterday there was a piece published in nature

reviews uh cardiology about transcendental meditation. I think the

transcendental meditation. I think the that shows that the world is changing.

you know, a clinical u uh 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 it improves well-being, this could actually be a treatment to help the heart recover, >> right? And to help treat a very serious

>> right? And to help treat a very serious um you know, life-threatening [clears throat] disease, cardiovascular disease. So, that's I suspect there's

disease. So, that's I suspect there's something with meditation. I have a a 10-minute every morning I sit down. This

is I'm religious about this. I wake up, first thing I do is sit down for 10 minutes uh with Sam Harris's waking up app. And I it just helps me connect

app. And I it just helps me connect ground, you know, connect with my energy. And then I think the for the

energy. And then I think the 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 um you know, mentally, but probably also

physically.

>> Awesome.

There's a lot of discussion about peptides.

MC Cuminin SS31 also called Elamma pretide. Didn't know that.

pretide. Didn't know that.

>> Uh GHKU copper and various BPC157 TB500 analoges. I told you this stuff's

analoges. I told you this stuff's getting popular. Um people are curious.

getting popular. Um people are curious.

>> Uh let me ask you this. I'll 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. uh would you let your sibling mom or dad inject these things?

>> No.

>> There were many questions centered around the fact that uh 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 the spindle and the formation of the embryo etc. And uh there the questions were specifically about uh the

recommendations of ubiquininal and CoQ10 urolithn. These are very prominent in

urolithn. 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 uh on urolithin a um that improves quality in cultured cells and then in animals. Um

so it's possible and it there I think I saw recently some very compelling data on sperm mitochondrial DNA uh content

mitochondrial DNA content like per sperm um linked 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. Uh I it could be that part of

society. Uh I it could be that part of the the issue behind this is mitochondria aren't um you know as as optimal as they should be and or energy

is not flowing as as uh freely as as it should be. Um so I don't know about the

should be. Um so I don't know about the the whether those treatments could solve the issue. My my sense is the issue

the issue. My 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 messing up our energy.

>> Last question, feel free to pass on this one. There were a number of people who

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. Mhm.

>> Uh this is, I realize, somewhat of a barbedwire 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

like that. But >> I don't know, I did an episode on fertility where I reviewed a meta analysis of data showing that indeed uh

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 um brain, sperm eggs?

>> If 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

be mitochondria. If you reason about this from first principles uh in the mitochondria there's a bunch of iron you know iron sulfur clusters which uh some of them at least are paramagnetic

meaning they interact with magnetic fields um 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 uh so that's for biological plausibility data I know some data where people have measured mitochondrial respiration, right? Which

is flowing electrons to oxygen and you see 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 uh and it

seems like there's there's there's an effect uh on this one function 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 uh used magnetic you know fields or 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 um and uh there are biohysicists like my wife Nosha Morgan who has done experiment experiments with

pattern magnetic fields which is uh different than just you apply a static magnetic field like with a 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 uh 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 c a certain pattern instead of uh with um

molecules like glucose and pyrovate and lipids and stuff and you're or light right now you're beaming energy in in another modality as electromagnetic

waves and uh and there proteins clearly that and iron sulfur clusters that can be sensitive to that. Um, so I think there's some biological plausibility.

There's evidence that this might happen and affect mitochondrial respiration.

Um, and um, 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

body. Maybe we can use those at some point to promote the healing process.

>> Love it.

>> So, we'll see.

>> We will see.

>> Dr. Dr. Martin Peicard, thank you so much. You gave us a master class in

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. Uh, and

the way you frame this whole notion of energy flow. And I guess we should

energy flow. And I guess we should credit your wife here for uh 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 uh 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 is just spectacular. Also,

spectacular. Also, >> you're reversing graying of hair. Um

people get you're giving people agency over that. And I just want to

over that. And I just want to re-emphasize that how incredible it is that you're approaching things at this very high level of subjective experience, this 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 biohysical mechanisms.

It's really spectacular. uh you're truly an N of one as as we say and I'm very excited for what you're putting together in terms of this uh scientific institute to solve healing your book. We'll talk

again later uh 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.

>> I'm 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

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