What's the deal?
Can people reverse the graying of their hair by reducing their stress?
Can people accelerate the graying of their hair by stressing more?
Likely both are true, yes.
Okay.
And I think what we discovered is that hair graying, at least temporarily, is reversible.
This was surprising because it goes against this notion that aging is a linear process that...
Just happens over time, no matter what you do.
And here we should know, actually a hallmark of aging, which is deep pigmentation, losing color in your beard and your hair.
It's something that happens to almost everyone, but at different stages of life and so on.
And then on the same person, and the reason we got into this was that this felt like the perfect experiment.
Every hair has the same genome.
They're all genetically identical twins, right?
And they're all exposed to the same exercise regime, the same food, the same stress levels.
Yet some hairs go gray when you're like late 30s and then some hairs go gray when you're like in your 80s.
What the hell's happening?
If we could figure this out, maybe we can understand why different people age at different rates.
Because it's very clear that there's no more than 10 of how long you live.
That's genetically driven.
Like the best studies put this at around 7%.
7% of longevity is genetically inherited maybe, and then about 90% is not.
Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life.
I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
My guest today is Dr. Martin Picard.
Dr. Martin Picard is a professor of behavioral medicine at Columbia University.
He is also a leading expert on how your daily behaviors and your mode of thinking, meaning your psychology, change energy production in your cells and can accelerate or reverse biological aging.
Most people have heard of mitochondria as the energy producing organelles within their cells.
And of course, that's linked to what we call metabolism and metabolic health.
And, of course, most people understand that eating properly, exercising and sleep are critical for metabolic health.
But it turns out that's only part of the story.
As Dr. Picard explains, mitochondria don't just make energy.
They act as sort of antennas to link your psychological experiences to your organ health, your rate of aging and your sense of vigor, meaning your mental and physical readiness.
He explains that how well your mitochondria work in different organs and brain areas reflects what specific forms of exercise you do, as well as how you think and how you manage stress.
Today he explains the things that you can do to enhance mitochondrial function that go beyond the typical get sleep, eat right and exercise advice.
His lab has shown that aging is not linear.
It's not just a progression from youth to death. where your mitochondria decline over that time.
At different ages and stages.
Mitochondrial health drops off like a cliff, but there are critical things that you can do in terms of how you eat, your mindset and exercise that can offset those changes.
His lab also famously showed that graying of hair is indeed related to stress and is also fortunately, reversible.
By the end of today's episode, you will not only have had a masterclass in mitochondria, he explains mitochondria with immense clarity so that you really will understand how these incredible organelles work to produce energy and as the sort of antennas to direct that energy from outside you and by the things you do.
And by the end of today's episode, you'll also have a lot of actionable items that you can apply toward your health and to offset aging.
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
It is however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public.
In keeping with that theme, today's episode does include sponsors.
And now for my discussion with Dr. Martin Picard.
Dr. Martin Picard, welcome.
Thank you.
Your work is so relevant nowadays.
I suppose it was relevant always, but These days we hear so much about mitochondria.
Most people have perhaps heard of mitochondria.
They think the powerhouse of the cell.
But you're 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 organelles we call mitochondria is not for them, keep in mind Martin's Laboratory was the one that discovered that you can indeed reverse the graying of your hair, that graying of hair is not a prerequisite of aging.
There's some other ways that hair grays.
So we'll get to that later.
Super interesting work.
I have a million questions for you.
Let's start off with the most important and most basic question, which is what is this thing that we call energy?
There's electrical energy.
We know the sun gives us energy, et cetera.
But when we're talking about the energy of life and Physical and mental vigor, the feeling that we want to do something as opposed to have to force ourselves to do it,
What is this at the organism and cellular level?
I mean, even physicists don't agree on what energy is.
And there's been debates.
You know, Richard Feynman, who 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.
Light energy, electromagnetic, kinetic energy, movement, speed, potential energy.
So energy kind of manifests in all of these different ways.
So, in a nutshell, I think the best definition I've heard from my wife Narosha, who's a biophysicist, energy is the potential for change.
And that applies to any kind of form, any form of energy you can think about.
It's the potential for change, for changing something in the system.
And that's, I think, an accurate description of thermal energy.
If something is frozen solid, there's no potential for moving something.
We need to be at 37 Celsius, the human body.
It gives us the potential to move and muscles to contract and our biology to... to function.
So this is just one example where there's a sweet spot of energy or there needs to be some thermal energy.
You need to be a little warm to be alive.
So the potential for change, and then it manifests in all these beautiful ways.
And it's something that flows.
A key property of energy is something that has the ability to flow and to transform.
You can never create nor destroy energy, right?
That's like a fundamental law of thermodynamics, but energy always transforms.
So you can transform heat into motion, right?
And like the steam engine, for example, through pressure, another form of energy.
Or you can transform electricity into, you know, a picture on your screen.
That's, you know, what your computer does.
Transforms your raw energy electricity into, you know, a picture, a sound.
So that's what happens all around us.
It's all you know energy moving, transforming energy from the sun right, this nuclear reactor in outer space beings energy at us.
And then what plants do is they take that energy, transform light into biochemistry.
And then you get energy, which used to be immaterial, that gets crystallized into biochemistry.
And then we, human beings, animals, eat that biochemical energy.
And then in our mitochondria, that energy gets transformed, right?
Again, the potential for change.
And then that biochemical energy gets transformed into an electrochemical gradient.
You charge your little batteries, your mitochondria.
And then that's another form of energy, which, again, is a potential for change.
And then you can make ATP with this.
You can make reactive oxygen species.
You can make hormones.
You can, you know, all of the beautiful things that mitochondria do.
So energy is that potential for change that has all of these different forms, that continuously transforms.
Amazing.
Or you can use your brain to create technologies that create other forms of energy.
Or, excuse me, transform other forms of energy.
Exactly.
And your question was about the human energy vitality, like 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 the human body, It kind of moves us into action, right?
And we know from first principles that the basis for human experiences, the mind and our ability to be inspired to feel positive things or to feel negative things depends on the flow of energy.
The difference between a thinking feeling, conscious person, having experiences and being able to go to the gym and lift, and a cadaver is really – it's not the size of the muscles, the number of cells, the nucleus, the genes, the mitochondria.
It's none of this.
The difference between a living person and a cadaver is the flow of energy.
Yeah.
When you die, all of the structure you know, the physical stuff, remains as is, but energy stops flowing.
If you stop breathing, if your heart stops beating, energy flow stops and then energy transformation therefore can't happen.
And then that's what we call death.
And then the mind dies, right?
Like you don't have an experience anymore.
And so the flow of energy, I think, has to be the basis not only of life, which we know, you know, to be correct, but also the basis of human experiences and what we experience as energy.
We think about energy, we crave energy and we know, and the way we talk about you know, this person has really good energy, or this thing you know really energized 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 most people will have, you know, had the experience of feeling really excited about something right.
A new idea, a new person.
And then you know you have butterflies and you know there are emotions going on in your body.
I suspect emotions, the best kind of first principles definition of an emotion is energy in motion.
And we can talk more about what we experience in terms of energy, but I think it's pretty clear we don't experience energy per se.
You don't have a direct experience, an empirical access to how much fat you have in your body.
There are hormones that communicate, and how much energy is in your liver or how much heat is in something.
What you feel, what you experience is a change in energy.
When energy moves, you feel that, right?
And I suspect that's what emotions are.
There's like a movement of energy, something shifts, and then you experience that.
A bit like if you're in a car and your eyes are closed and you're going constant speed, right?
Kinetic energy.
You have no way of knowing from first experience if you're going at 100 miles an hour, 10 miles an hour or if you're standing still.
These are very different energetic quantities, right?
The kinetic energy.
What you do feel is acceleration and deceleration.
You feel the delta in energy.
The change in energy, acceleration, deceleration.
Same with temperature.
If you touch something and it's body temperature, the same temperature as your hand, you don't feel it.
You don't feel room temperature or body temperature.
What you feel if 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.
It's the heat of your body leaving through conduction towards this.
And then that's what you experience.
And if you touch something that's hot, you're not feeling the energy of the thing.
You're feeling the heat that's coming into your body.
So you feel that delta and that change.
And that's how human perception also works.
We're able to see colors, to see light.
You've studied the visual system a lot.
Fundamentally, the ability of the eye, of the retina, to perceive, to sense light, requires that you bring photons that are beaming from whatever source.
Short, long wavelength.
You need to bring them into stillness.
You need to resist the flow of photons.
So you change the speed of the photon, and it's that change in energy.
You get kinetic energy speed of light and then boom when the delta V, the change in speed, happens.
This is when you can trigger a calcium release and then molecular series of events and action potential.
So in order to see, you need to resist the flow of photons.
You need to resist energy movement and then that triggers a transformation.
Same for hearing.
We hear and I hear your voice because my eardrum resists the pressure waves that you're producing.
So your energy is being channeled and projected through the air as sound waves, another form of energy.
And then I'm feeling you through your energy that's carried through the air, and then, because my eardrum resists the pressure wave that you're producing, and then it's that resistance and that change that delta again in speed by resisting the sound waves coming from you, by resisting your energy.
Now I can perceive them.
And then there are little ossicles 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 to 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 are many, but that electricity is just so amenable to computation, processing and integration.
Once you have this common energetic language for sight, for hearing, for touch and smell and taste, then you can integrate that.
We perceive energy transformation and change in energy.
We don't perceive energy per se.
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Your description brings to mind a number of things, but years ago a colleague of mine, who unfortunately now has passed, stopped me in the hallway at Stanford.
This was Ben Barris, my postdoc advisor, later my colleague as a faculty member.
He said, why do we have so much less energy as we get older?
And I said, well, that's probably not a concern with you, Ben.
I mean, he was known for having tremendous amounts of energy.
He probably only slept four or five hours a night.
But in any case, I said, I don't know.
And he goes, well, how come no one's working on that?
Like, why are we working on all this other stupid stuff?
And I won't tell you what he listed off because some of it was stuff in his laboratory.
And I said, well, that stuff's interesting 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 when we're young as opposed to older.
You said something interesting, very important to underscore and that I'd like to get into a bit more, which is you said you know your partner said energy is the potential for change.
And you mentioned emotions, they stir us, right?
And that that feeling, especially a positive anticipation is so much of what we live for.
In fact, the signature feature of major depression is lack of of kind of any idea that there is a future worth living into.
So apathy, et cetera, whereas vitality and excitement and everything good about life is about wanting to know what comes next.
So if we take a biophysical, to cellular, to psychological set of steps here, we would say that somehow energy is converted into this internal vibration which we call emotions, that let us physically sense into a future.
Mm-hmm.
It could be even a negative emotion, but it still senses into a future.
And then you give this example very dramatic example but I believe appropriate of a cadaver where all the material is still there, right after death, before it degrades, right.
But it can't move, and therefore there is no future.
And it can't sense.
It's a very different way of thinking about death.
So...
Let's talk about psychological energy and physical energy that we call vitality.
And, if you would, it's a bit of a challenge, but could you perhaps use that as an opportunity to teach us about these incredible organelles that we call mitochondria?
I use a slide often as an opening slide when I give presentations to academics or non-academics, which is kind of a mitocentric view of the world.
At some point we realized that the Earth was not the center of the world, and then we switched over to a different form of, a different model of the universe.
So my sense is we need to do something similar in biomedicine.
We still have, I think, in most... people's mind, especially the older generations, a very gene-centric, you know, nucleus-centric view of biology that the genes are there and then central dogma, right?
The genes drive RNA, drive protein, and then drive phenotype.
And we know that that's not the full picture.
And there's a lot of end phenotypes, for example, in 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 can't be encoded in the genes somehow.
We found recently that actually there are differences in mitochondria.
Part of the reason why these animals behaviorally, are different, maybe half of the variance, half of the inter-individual differences.
What makes one mouse super chill and the other, the brother or the sister that is genetically identical, very anxious, has to do with energetics in some way.
I use this slide to convey this mitocentric perspective.
If you want to have a copy and show people, I'm happy to share this.
One way to understand this is energy comes into the organism as food.
We eat and we breathe to fuel our mitochondria.
So the reason you breathe is to bring oxygen into the body.
Most people know this.
And then, once oxygen is in your lungs, it goes into your blood and then it goes to the heart, and then the heart, kind of boom, distributes this across the whole organism.
And then, when oxygen gets to your big toe or to your muscle or to your neuron and your hippocampus or some brain region, What happens is the oxygen enters a cell and then, once it's inside the cell, it looks for mitochondria.
I mean, it's attracted by a concentration gradient.
So the mitochondria is where oxygen is consumed.
And then when mitochondria consume oxygen, they basically create a downhill slope for oxygen, to kind of be attracted to that.
So you breathe to bring oxygen to your mitochondria and you eat to bring electrons into your mitochondria.
And what happens?
There is this beautiful sequence of reactions where you have electrons that were initially stuck on food by the plants, taking solar energy to stick electrons onto carbon, and then you make hydrocarbons, and then that's glucose or starch, and then oils lipids, everything that that's good fuel for mitochondria.
Those things, the food and the oxygen, converge inside the mitochondria.
And then finally, the electrons that were ripped off as CO2 is broken into oxygen are reunited in your mitochondria.
And so your mitochondria actually make water. and then release CO2.
So they close the life cycle that we have with photosynthesis.
Photosynthesis makes oxygen and food, and then our mitochondria brings those things together and then they release water and CO2 exactly what plants need.
So it's this beautiful cycle.
So when mitochondria do this, is basically feeding unpatterned energy into the system.
And it starts with the mitochondria.
The same way that if you feed electricity into a Morse code, right like teet teet teet teet teet teet, 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 nothing.
It's just raw current.
And then you pattern it in something that means something.
Short beeps, long beeps.
And then you can spell stuff.
You can communicate information.
So you're creating information by patterning in time, by patterning electricity.
So mitochondria, the way I see them is they're kind of an energy patterning system.
And we've called them the mitochondrial information processing system for that reason.
Should we think of them like a little Morse code lever?
I think it's a decent analogy for 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 the transformation of energy right.
The electricity can be converted, transformed into all sorts of different messages signals, right with your Morse code, depending on the needs, depending on the state, depending on the person pressing releasing the lever.
And sometimes the organism needs a lot of ATP.
If you're a mitochondrion 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 mitochondrion in the liver, your job is very different.
And you're a very different kind of mitochondrion.
Mm-hmm.
Well, let me ask you this.
I think you just answered the question, but are there different types of mitochondria?
Yes.
How does a mitochondria in the liver versus in the brain, versus in the heart know to take the energy that it's transforming and pattern its output so that heart cells can do what heart cells need to do, or liver or brain?
This seems like a very important issue.
Yeah.
Is it possible even that the mitochondria and these different tissues are fundamentally different organelles?
We should probably define what an organelle is for people.
Yes.
Organelle is the technical term for an organ of the cell.
The cell typically is represented as this skin.
And then inside the skin is the cytoplasm, the big soup.
And then inside the soup, the cytoplasm, there is a bunch of little organs that allow the cell to do all sorts of things and perform its activities and replicate and so on.
Mitochondria is one of those organs.
And their purpose is to process, transform energy.
And one of the ways in which they transform energy is taking raw energy from biochemistry, the food you eat, empowered by oxygen to flow those electrons and then making – building a charge and then powering this beautiful rotor.
Some people might have seen this.
It's kind of a rotary – engine kind of thing, a turbine.
And then, 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 in the backdrop of all this, of course, is that all of this self-organizes during development.
The yes, the genes are the blueprint, but this is all built up from scratch.
Probably a tangent for another time.
But so how does a heart cell know to produce a lot of atp versus a liver cell?
And, Of course, it's coordinated in time with sleep and circadian stuff.
But how does it know, or does it even know?
I'm a mitochondria inside a heart cell and the amount of energy I need to transform is X.
Yeah.
How does a mitochondrion, right?
Singular is mitochondrion and multiple is mitochondria.
How does a mitochondrion in a heart cell know that it needs to be a cardiac mitochondrion?
Right?
Is that your question?
Yeah.
Is it genetically different than a mitochondrion from...
The liver?
No, they're genetically exactly the same.
And that's another kind of punch to the gene-based model of biology.
How could it be that every cell in your body is genetically identical and the mitochondria have their own genetic material?
We all have our mom's mitochondria, which is really beautiful.
100% of our mitochondrial genome is from mom.
Is that true?
Correct.
And there were a few papers a few years ago that said, oh, no, look here.
There's this one case.
This one kid or these two kids that have paternal father mitochondria.
Turns out it was like a mistake in the sequencing.
So mothers are truly always right.
Yes, power to mothers.
People will be thinking and I'm also thinking does that mean and of course there are lifestyle issues, but does that mean that if we were to look at the quote-unquote energy levels of mom versus energy levels of dad, that what better predicts the energy levels of mom?
A kid is the mother's sort of baseline levels of energy at a given age.
I don't know of studies that have asked that question about, like subjective energy or like the energy to do stuff, and which we can.
I think we'll talk more about.
But people have looked at other more tractable which.
What we do in biomedicine we take things that we can measure objectively or, like you know, run on the gel or sequence or you know objectify with a biomarker in the clinic.
People have looked at longevity, right?
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.
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?
Some evidence say it's more maternally inherited than paternally inherited.
So it could be that part of your ability to live a long healthy life, or your risk or your resilience to those disorders really are conveyed or carried by mitochondria, by your ability to transform energy.
And the reason why through evolution –, your uniparental inheritance, you get your mitochondria from a single parent has developed.
Most people think is because there needs to be a really close metabolic, energetic match between the mom and the baby.
The baby comes out and then if the mom has a certain type of metabolism and we're all different, I hope we talk about how different we are energetically, metabolically.
So we're all very different.
If the baby that was born was like, so metabolically different than the mom, there's a chance that there would be a mismatch, right?
And then the mom wouldn't be able to support through breastfeeding historically.
That's how babies survived.
And that would be a catastrophe.
So you know, it's probably a good system to have baby metabolism match pretty closely because they have the same mitochondria as the mom to mom metabolism.
So that's, I think, a loose hypothesis, but it makes a lot of sense.
It does make a lot of sense.
Every mitochondria you have in your body, like the brain mitochondria, neuron mitochondria, astrocyte mitochondria, whatever your favorite cell type is your heart mitochondria, liver mitochondria, muscle mitochondria they're very different.
And now we have a new method.
There's a wonderful scientist in our group, Anna Monzel, who's developed a method to profile different types of mitochondria.
We call this mitotyping.
The same way that now in neuroscience or in immunology.
It makes no sense to talk about a brain cell or like an immune cell.
If you're a self-respecting immunologist, you know your cell types and there's at least 30 different types.
So I think we're at this point in mitochondrial science where we need to adopt a similar level of specificity.
There are different types of mitochondria.
We call those mitotypes.
And they emerge, all of them, from the same mitotype in the egg, right?
The egg that the mother carries and releases from the ovary.
There's about half a million mitochondria in that egg.
And then those mitochondria, there's a single type of mitochondria in there.
And then when it's fertilized, development happens in this beautiful 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 cell types of organs.
And one way we think about this is I think it's it makes a lot of sense to think about mitochondria as social organisms.
And there are multiple features of mitochondrial biology that obey what behavioral social scientists classify as social
If you study ants, for example, there's a few rules that we know.
Ants are social creatures because they form groups and there are different types.
There's division of labor.
You have worker ants that work really hard and you have warrior ants that are really chubby and they're here to defend the hive.
They like to fight.
Yeah, exactly.
So those two types of ants, you look at them side by side.
There's this little flimsy, super active worker ant and then this chubby warrior ant.
Genetically, they're identical.
They have the same genome.
They came as a little larvae from the queen.
But their morphology is super different.
Their behavior is very different.
But through development their cues are different to the different larvae, and then they end up becoming a worker or a warrior.
So the same kind of thing happens in mitochondria.
So there are different types of mitochondria, like the two types of ants.
There is division of labor.
There's some mitochondria, for example in the muscle, that are at the surface of the muscle, like just underneath the sarcolemma the, the skin of the muscle cells, and then their mitochondria that are inside, where the actin myosin, the contractile proteins, happen.
Subsarcolemual mitochondria and intermyofibrillar mitochondria, two populations.
Their proteome is different.
Their molecular composition of those different types of mitochondria are different.
Their functions...
ATP synthesis, reactive oxygen species production.
Their ability to handle calcium and release calcium is different.
Their morphology is very different.
So even within one cell, you get this division of labor and differentiation of mitochondria.
And in every cell, mitochondria have a life cycle.
New mitochondria are born and old mitochondria die out, which is what happens in social creatures.
And there's a few other features like this that I think make mitochondria social organisms.
And once you start to think about mitochondria as social creatures, then you understand maybe a little better why they need to fuse with one another.
And if you ask Google what do mitochondria look like?
Or chat, GPT or whatever, it shows you always the same kind of images.
It's like a little bean.
You brought one as a gift.
At one moment, I thought they might be brass knuckles when you first handed them to me, but it's a mitochondrion with the cristae of the mitochondria.
There you go.
Usually looks like this, but you're saying, in reality, there'd be many of these closely fused to one another.
Yeah, and when they fuse you get these like bean or kidney shapes or peanut shape.
Whatever your preference is that fuse with one another.
And then they form these beautiful filaments.
So if you're lucky enough to work in a lab that has one of these cool microscopes called confocal microscope or light sheet microscopy,
And then you can make the mitochondria fluorescent.
So you put a dye in the dish and then it's a little fluorescent molecule that goes inside the mitochondria.
It's attracted by the big charge that mitochondria have.
And then you turn off the lights, look down the eyepiece, and then you see this beautiful filaments, mitochondria moving.
They move pretty slowly.
And interestingly, they're just at the edge of human perception of how quickly we can perceive things to move.
So they move barely fast enough so you can see them.
And then they kiss and then confuse completely.
Either you can invite everyone to your lab to see this, but that's a lot of people.
You'd be very busy.
We'll put a link to a video of this.
We're building a webpage called MitoLife, which is to help people understand themselves energetically and through the beauty of mitochondria.
And there are all sorts of different types of mitochondria that move differently.
And when the mitochondria are not healthy and if they can't flow and transform energy properly, they start to look really weird.
It occurred to me that you know for the longest time I'm 50 now, so I can say for the longest time, for the longest time we heard, that if we want energy we need to eat right.
Of course we need to sleep, but we need to eat.
So it'd be like, and every kid learns, you're consuming energy so that you'll fuel your body.
There are 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, et cetera.
I think you should be an omnivore.
Some fats, yes.
That's 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 that, and based on what you're saying, it should be clear to everyone that the issue is not lack of energy going into the system.
It's that the transformation of energy that occurs in mitochondria somehow is not happening correctly in people that are obese or in people that are eating and feeling lethargic.
And of course, there's blood sugar aspects to this and we could discuss all of that and we won't because that's not the topic for today.
But I think, if nothing else, that people can just understand that they have not just these powerhouses, but these power plants within their bodies that are transforming the energy, and the mitochondria are central to how the energy is transformed and distributed on an organ by organ basis.
I think that would be a helpful concept for people to get into their mind, because people are talking about mitochondria all the time.
People are talking about and hearing about nutrition all the time.
And so often we just think about calories and you know, everyone knows that.
You know calorie is a unit of, you know heat off, but when you burn a given food, 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 how their bodies work and you're adding a lot of important detail and aspects to that today.
So I just wanted to frame that up.
If you have any reflections on that, great.
If not, it was just a point that came to mind that I think might be useful.
Yes, it's so important.
And we are energy.
Fundamentally, we are the flow of energy through this biological infrastructure that we call the body.
But you are not the cells or the genes or that thing.
You are much more that energy that is flowing, which is why, when the energy stops flowing, you are no longer.
When you die, all the physical stuff remains, but you no longer have an experience.
You no longer exist 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 gazillion nouns.
And so I think people thinking about themselves as a verb state of an energy transformation being.
It sounds so mystical, but it's not mystical, it's biochemical.
I think could be useful.
Along those lines.
I do want to talk about this recent paper that you published, which essentially my understanding is that looked at different brain areas and found that different brain areas have different concentrations of mitochondria.
And we know that different body areas and different organs have different concentrations of mitochondria.
But I heard you say someplace and this is such a beautiful, sticky topic, as they say that perhaps the things we do in life maybe lift weights, maybe study biology, maybe play the piano, maybe some combination of things 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 weight lifters.
Something else
But in the brain, this gets very interesting.
This means that if we read poetry, for instance, or study biology, that the areas and circuits of the brain that are responsible for that in some sense become better at doing that.
And I think this is a very important topic because it really gets to the essence of who we are as individuals, based on our choices of what to do and what not to do.
So, with that 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 would love that we flow as energetic processes, right.
To your point, like we are transformative processes.
Like we transform, we flow, we are the energy that flows.
And the more you direct energy to one area, right?
If you go to the gym and you do bicep curls like you're resisting the flow of energy while you're contracting, And then you do this a few times and then when you go you get blood flow right.
Energy flow through the system.
And we know exercise training is a beautiful example.
If you're trained to run a marathon, for example, you can double the number of mitochondria in your muscles double.
And my understanding of this is as energy flows through the existing mitochondria, you're basically bringing your energy into that system.
And then the biochemical energy gets transformed into molecules, into metabolites and then eventually into proteins.
And then structure gets created as energy flows.
So it's the flow of energy.
First, you resist it.
We call this energy resistance.
And then when you let go of the resistance, that's when we build.
That's when we grow.
That's when – right?
Arnold Schwarzenegger said muscles are torn in the gym.
They're fed in the kitchen and are – grown in bed, I think.
In an Austrian accent.
Yes.
So if you direct energy towards a muscle, then one way to direct energy is to resist the energy flow and then to let go.
And that's what exercise fundamentally is.
You resist the energy flow and then you let go.
When you resist energy too much, it feels uncomfortable, which is the burning pain.
And then when you let go is when growth and you know, building can happen.
And we know the same thing happens like everywhere.
This is not like a mysterious thing of the muscle and like of exercise, you know, physiology.
This is a fundamental biological principle.
If you flow energy in one area, then it will grow.
It will 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 damaged, then the muscle doesn't contract anymore.
You're basically blocking the flow of energy there.
And what happens?
It atrophies.
Atrophy is a normal movement of life when energy flow decreases.
And if there's no energy flow, there's no purpose for that structure.
If you feed, if you stimulate that structure, be it a muscle or brain circuit, right brain network or brain area, then naturally you know that area should grow and build.
And 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.
Now we know very well if you overeat right, you eat more than your body is actually flowing, consuming in terms of energy transforming.
You get sick.
Like if you can, you put on fat, which is a good adaptive diet. coping mechanism to eating too much.
But then eventually the system gets overwhelmed and then that hurts the mitochondria and it hurts cells to become insulin resistant.
And so there's all sorts of consequences to eating too much.
You cannot eat more to get more energy.
And that is, I think still scientifically a very big mystery, right?
That.
Why can't we just ramp up our energy, energy transformation, and then sleep less and work out three hours every day?
Even professional athletes who devote all of their energy to building muscle mass, building skills or building aptitudes.
There's a limit to how much you can eat.
We don't really know why that is, why there's a limit to that.
So the body operates an economy of energy.
You have X amount of energy.
You can push that up over short periods of time.
Like if you start to work out and you're a cyclist, you do the Tour de France.
Three weeks, you're going for like 5,000, 7,000 calories a day.
You do this for three weeks.
There's a reason why the Tour de France is not four weeks and five weeks.
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 if you look at that curve you know 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 400 meters, and then it goes down.
And the Tour de France is, you know, marathon is here, Tour de France, three weeks is here.
Then you get that crazy run across America, multiple weeks.
And then at the very end, nine months, Pregnancy.
And it costs energy to grow a human being.
And some of the data suggests that when you grow a human being for nine months, the woman is basically operating at the max of her capacity.
If you integrate over a nine-month period, do pregnant women accumulate more mitochondria or the energy demands are entirely for the mitochondria of the developing fetus?
That is a good question.
We know certain brain areas grow during pregnancy.
That the brain remodels, exactly.
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 a slightly different way, and it's not just about yourself.
So there are certainly even long-lasting brain changes that happen in the woman's brain.
So this economy of energy between organs is likely, what explains, if you're a young woman and you exercise a lot, you lose your menses amenorrhea.
And this is not because the reproductive system is broken or because the ovaries are sick or something like that.
The best explanation we have is there's a shortage of energy.
Like you're pushing and driving all of your energy budget towards your working muscles, towards making more mitochondria in your muscles.
And there's no more energy to fuel 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 more lethargic and tired?
And these are very adaptive.
And we know we need to rest, but it's not just about getting sleep.
We actually need to slow our circulation down.
We need to rest.
And there are all these theories, you know, about do you feed or starve a cold or flu?
And I covered that in a different episode.
I will put a link.
It's not straightforward, but follow your appetite, stay hydrated, keep your electrolytes up, and so forth is the short answer.
But is it that the immune system needs more energy and the body, as a protective mechanism, as an adaptive mechanism, is saying slow down everything else and devote yourself to 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 idea?
Yep.
I think that's the best model we have.
And I had a personal experience of this over a New Year's a couple years ago, where I could feel I was, you know, coming down with something before the you know New Year's dinner.
And so it ended up being a pretty short night.
I went to bed early and that night was terrible.
The next day I was so, so off and I was, you know, starting to work on the book Energy.
And then I thought oh, this is such a cool opportunity like now I'm experiencing.
I'm feeling drained, right like I'm in bed, everything hurts.
And then I thought I should be writing about this, right like.
And then I thought like, just the thought of, like grabbing my computer, then I shouldn't cost more, doesn't cost a lot of energy, just like wiggle my fingers on the keyboard.
But you know, there was no drive.
I stopped caring about stuff that I usually care about right.
Everyone has experienced this when you're really sick.
Motivation, right?
Zero.
My capacity to be the best human being that I am and to be kind.
A little diminished.
Just like I was just trying to fucking survive.
And what we know in terms of biology and mitochondria and energy.
That happens when you're fighting something like this.
The immune system costs a lot of energy.
Mm-hmm.
So I think the best model interpretation we have of sickness behavior is what you were describing.
The technical term is you feel sick, right?
And you don't want to move.
The body, you feel cold, right?
Which then forces you to put covers or, you know, to dress, to avoid cold environments.
Mm-hmm.
It hurts to move your body, like to contract muscles and like there's allodynia, right?
You become more sensitive to pain.
All of these things likely exist in service of conserving your precious energy budget.
And even not eating, right?
Like follow your appetite, yes.
And eating costs energy.
Nothing in biology is free.
Everything costs something.
And if you eat food, now you need to masticate.
You need to have peristalsis.
You need to have gastric acidification movement, secreting digestive enzymes, maybe some bile.
The orchestration of digestion is pretty expensive.
It's like 10%, 15% of your daily energy budget.
So that's 10%, 15% of your daily energy budget.
If you're running a limit, it's a lot.
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You mentioned that if women exercise beyond a certain threshold, they stop menstruating.
And that it's because there's not enough energy, essentially, to menstruate.
One idea would be, well, if you just eat enough, then you have enough energy.
But we have to think in verb states, not absolutes.
And so what I'm realizing is that, while one needs sufficient energy input in the form of food and this could also be true for the example of being sick it's necessary but not sufficient, because the mitochondria are doing two things.
They're transforming that food energy into bodily energy to menstruate or to move or exercise or think or care about a book, et cetera.
But part of their job is not just to transform the energy, it's to distribute the energy.
And so you really need two conditions.
And I'm not a computer scientist, but I know enough about programming and engineering that this concept of an AND gate.
You need sufficient energy coming into the system and you need to be able to distribute that energy properly in order for something to occur.
It's an AND gate.
You need both things, basically.
So I now and forever going forward, will think about mitochondria as not just energy production but energy distribution organelles.
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 gonna force myself to eat, provided I have enough body fat stores.
I need to eat eventually.
But whatever weakness or fatigue I feel is probably in that situation where I don't have an appetite is probably not a lack of caloric energy driving that fatigue.
It's that my body is saying you know what.
You're better off just not having me shuttle that food energy through you, so I can shuttle your immune cells to the proper place.
Exactly.
And this is when people say the body is smart.
There's an intelligence to the system.
I think that's true because with our brains, we think, oh no, I'll just cram more energy into that.
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 agree.
The body is wise.
Animals who don't have a very other non-human animals, like your dogs, they don't have a mind to distract them from living in alignment with their energetic states.
So when they're sick, the immune system just the amount of the part of your budget that gets consumed by the immune system expands right.
So this energy, this extra energy, needs to be stolen from somewhere, because you can't eat more to have infinite energy.
So where is that energy coming from?
So not contracting your muscles because you feel in pain is a good way.
Not having to thermoregulate because you cover up, another way to conserve energy.
And then stopping to care about stuff like becoming asocial and apathic and all of those features of sickness, behavior or energy conserving strategies.
And not eating.
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.
The record actually for not eating is from this Scottish man, 382 days.
Was he fat when he started?
He was very fat.
Was he fat when it ended?
He lost, how much he lost?
Like 250 pounds, I think.
That's a lot of stored sandwiches.
Yeah.
So most people can go a full month without eating.
And this maybe goes back to what we talked about earlier.
We don't feel energy quantity, right?
If you close your eyes and you feel your energy like you don't feel how much fat you have on your body, how much glycogen you have in your liver or, you know, in your muscles.
What you feel is the transformation of energy.
The neural energy.
Do you want to do a little experiment?
We can do a little experiment to feel our energy.
Definitely.
Yeah, okay.
By the way, a tenured full professor at Columbia School of Medicine just said 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.
Good things have happened in the world.
The reason we both closed our eyes and kind of stopped moving our bodies which is kind of what you do if you want to meditate or something like this is because it turns off the noise.
Mm-hmm right, and the.
If you want to survive in a dangerous physical world you need to be aware of, like stuff that might hurt you right or kill you um, and feeling your body, like proprioception, and all of this needs to be very high level.
It needs to be prioritized over whatever interoceptive you know signal there are.
There's some interoceptive 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.
We'll talk more about some incredible results about meditation and restoration of energy.
Can the audience do this along with us, provided they're not driving?
Yes, yes.
Okay, great.
So to do this, best is you're sitting comfortably and you can close your eyes if you want to.
I think that helps with the process.
We'll take one breath in and then we'll hold our breath for a little bit.
So breathing in, breathing out, and you can breathe out all the way, all the way down, and then hold that breath.
And for the first few seconds, it's generally not too uncomfortable.
But then as you hold this, feel into your body, to your belly, into your chest, into your head.
What's the effect of not breathing?
And then you start to feel maybe this urge to breathe and this desire to bring oxygen into your body, to your mitochondria.
And when you need to, you take a breath in, you can open your eyes.
If you can't hold it longer, you do.
What did you feel?
So when I went to the full exhale and held my breath, my, what we geek speak, what neuroscientists call interoception, my perception of things from the skin inward became more salient and I could feel my heartbeat more and more.
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, As the impulse to breathe started to kick in, 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 inhale, there's a relaxation of that sense.
Yeah.
There is the sense that energy moves out from the center.
At that point, like you'd feel more of your body.
Because I think anytime we don't have air, our brain goes to how do I bring air right here, right now?
You're not thinking heartbeat, you're thinking get air.
Something of that sort.
Yes.
I think if you do that and the urgency, the anxiety, the stress, it feels dangerous.
And I think to many people, Dying by drowning or suffocation is one of the worst deaths.
So why is that?
What is that sense of urgency, of anxiety?
It's CO2 building up in your blood.
CO2 is the product that mitochondria release as they transform energy.
And then when CO2 builds up, it means oxygen is getting depleted.
If oxygen gets depleted, the electrons from the food you eat can no longer flow.
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 ceasing to exist.
Not being able to breathe, being out of breath, is an existential threat to your energetic self.
Without getting into the details, I've talked about it on other podcasts.
I had a scuba diving accident a few years ago, 2017.
Ran out of air in a... in a bad situation to begin with.
And I'll tell you the sense of urgency is very immediate.
And fortunately didn't end up with any PTSD from that.
It obviously worked out okay.
I'm sitting here and talking, but 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 moment, the sense of urgency that kicks in is very intense and very, very fast, which speaks to just how hardwired these circuits are.
Because at that point presumably there was enough air to stay under for another five seconds, or whatever it is.
But when we anticipate getting oxygen and we don't, there's a big increase in stress.
Energy goes straight to whatever areas of the brain amygdala and other areas presumably that are like this is a bad situation.
Do anything and everything becomes about resolving the situation.
Yes.
And that's because we are energy.
We are the flowing energy through the system.
And if energy starts to stall, it just feels so uncomfortable.
We have to have evolved to 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 survive.
So what's trying to survive is not, like, the physical body.
It's this flow of energy that's, you know, being threatened, right, from lacking oxygen.
Many times already, you've talked about the flow of energy, and that concept, I think, is going to be threaded through as we go forward.
When you hear about practices – like tai chi, or when you hear, like in the martial arts, where people are taking other people's energy and, you know, converting.
And this is a not just a thing of like, of aikido, but the notion that like, if you box, you learn that you you're not just hitting with your arm and your shoulder, you have to keep your feet planted, you're pulling from the floor.
In some sense you're transferring the energy, you're actually pushing back against the floor and then it's coming up through your body.
People talk about the fascial slings.
You know, when people run they're, they're a they're bazillion different variations on this, but it's all about this concept of flow of energy.
And I find that so much of what we find incredible when people dance, when people sing, when people do incredible athletic feats or channel everything they've got into something.
This channeling of energy is the human animal deliberately channeling all their energy in the form of practice into something.
In many ways, we love that, even though By definition, it creates a very lopsided person.
And I'm not trying to get into the psychology of this so much as I want to go back to this notion of our brain areas having different amounts of mitochondria, probably from birth.
But then if we play soccer and we like math and pottery, we get a different brain 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.
Is there a trade-off?
Is there a trade-off?
Because I believe in staying fit and staying healthy and living a long life, but most people are not competitive athletes.
Most people don't want to be the strongest person in the gym or the best runner.
Most people, I believe, and I'm one of these, I want to be strong enough.
I want to have endurance.
I want to have some speed.
But I want to be able to think.
I want my mitochondria balanced across all my systems.
My girlfriend would say, well, you're a Libra.
Of course you do.
But I'm saying I want it because I want to be able to lean into a lot of different aspects of life.
I don't want to become the atrophied in one area and hypertrophy to some great extent in some other area human
So what are your thoughts on these through the lens of the results that you recently published?
Is it a trade-off?
I don't think we know exactly, but we did a study recently that points to the fact that there might be trade-offs between different systems.
Sorry, meatheads.
No, I'm just kidding.
I love working out in the gym, but you have to read too, you know?
You know, we tested the hypothesis that if you have more mitochondria in your muscles, you also have more in your brain and in your heart and in your liver and in your skin.
And the result is that's not the case.
And, you know, you, Andrew, I think you seem to derive a lot of fulfillment and, you know...
You live up to your full potential when you can do all of these things, right?
And you're a great communicator.
You're a great integrator.
You know, the kind of thinking you do is like this beautiful integrative thinking, which might be what has led you to do what you do now right, with most of your time.
Because this really taps into your strengths.
It really moves you.
I suspect, energetically.
I enjoy it.
You enjoy it?
What does that mean?
Enjoyment is kind of an emotional state, an affective state.
It's an energetic state.
We're all different energy transformers.
You transform energy and you have this ability to do what you do.
Other people have very different skills and gifts.
I think we were born with something that doesn't seem to be fully just encoded in people's genomes.
There are genetically identical twins that have very different aptitudes and personalities.
And we don't know where this comes from.
And then we are fed, we're moved and inspired by different things.
And when people seem to follow that, it appears to bring them energy.
And what this means biologically, the level of mitochondria.
I think our research is starting 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, or colleagues in Chicago asked people before they died how much sense of purpose do you have in your life?
How meaningful social connections, well-being, right?
And then the negative stuff, depression, loneliness, anxiety.
And then every year they answered those questionnaires.
So we knew how these people felt about themselves, about life, about some – greater power beyond them.
And then they died, gave their brain to science.
We got a little piece of brain and now we're measuring the mitochondria.
And Carolyn Trump, a researcher who works in our group, who's a bona fide mitochondrial psychobiologist.
So she asked questions between the psyche and the biology of mitochondria.
So she asked could it be that how people felt before they died relates to the mitochondria in their brain and the prefrontal cortex, the DLPFC, the dorsolateral prefrontal cortex?
And what she found is that people who felt more purpose in life and who felt more connected to others and who felt, you know, well-being for 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 they're fortunate to have or that they're actively fostering in their life?
That's actually transforming the mitochondria in their brain.
Maybe.
Or it's the other way around.
For some reason that we don't understand, they have more of the energy transformation capacity in their brain mitochondria and that is leading them to experience the world as more positive and as more purposeful and as more meaningful right.
Animal studies say it probably goes both ways.
So if you tweak the mitochondria in a rat brain, you can change the behavior of that animal 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.
And then the other way around.
If you chronically stress animals, you deprive them of kind of freedom of choosing different options.
So chronically stressful things actually damage the mitochondria in the brain.
And 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, and that the mitochondria in our brain can also influence our states of mind.
And if we want to talk about the philosophy of this, thinking about what's causing what maybe isn't really the right question to ask, but what's emerging that's relevant to your question, there's a clear connection between the subjective experiences that we have, that we know from first person to be meaningful, because that's what we have access to primarily is how we feel, how we experience the world.
Somehow is related to the biology of the energy transforming units, energy processing units in our brain.
And maybe also in the immune system.
And so we've done work in immune cells and brain tissue.
And we're currently analyzing mitochondria from 5,000 human brain samples.
That's 10 different brain and muscle samples from 500 people.
Do you have histories on these people, as to how much purpose, what they did, how much life fulfillment they had?
I'm so glad that biologists like you exist.
I just want to say that, not just because you're agreeing to be a public health educator, but 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 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 mitochondria in a laboratory at some medical school, at an Ivy League medical school.
But you're merging these ideas 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?
Now we can't respond to everything as just 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?
I think people confuse drama and friction with certain people.
It's like, that's energy expenditure.
That's not a good transformation of energy.
And you hear about this stuff now more in the psychology relationship space.
People will say, they're not good for my nervous system.
It's so funny how neuroscience is now Or I just feel relaxed around them or I can sleep next to them so comfortably.
And, you know, we kind of write these things off as like, oh, that's cute.
That's kind of woo.
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 biomedicine.
Many years ago, 50 years ago or so, there was this wave of whoa.
There's DNA that exists and there's proteins.
We can sequence stuff.
We can measure the components of a cell and we can look at things under the microscope and we can scan the brain and all of those things, assets that we were all of a sudden able to capture.
It was really convincing, compelling.
We built a whole research and academic science ecosystem around this.
And I think by nature, this reductionistic framework pushed aside the mind. right?
All of the subjective experiences, you know, it's in your head or 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 energy right.
And matches what matters for you and what you really care about.
So pushing aside which is what biomedicine has done, pushing aside the mind and all of those subjective experiences, I think has been really damaging to understanding the basis of health and understanding what allows some people to be healthy for a really long time and to live long, healthy lives and to live fulfilled lives.
If we think of ourselves as molecular machines, There is no way we can make sense of this.
And then we have consciousness research that's trying to make sense of this beautiful spectrum of human experience right,
From like, I can't get up in the morning.
Taking a shower is too difficult, and I'd rather die.
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 and I can do good in this world.
And then everything in between.
And we're left now.
We don't have a science of this.
We've said this is not science, right?
This is like psychology.
This is woo stuff.
And we can't access this with biomolecular science.
And I think it's true.
I don't have a lot of hope that we will make great inroads in fully capturing the nature of consciousness, the nature of the human experience, the nature of well-being, of what it means to be a fulfilled human being that lives up to their full potential.
I don't think... at this point that 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 a flow of energy, not as the molecules and the metabolism that support this flow, but as the flow itself.
I think that is kind of a point of consilience.
Energy flow is the linchpin between matter, you know, the stuff of biology, and experiences.
Again, we don't experience energy itself.
We experience a transformation of energy.
When energy flows through this metabolic circuitry that we have.
Metabolism is just an energetic circuitry electrons flowing not as free electrons in a copper wire but as electrons from food to oxygen through enzymes, right.
So this thing is a metabolic... carbon-based energetic circuit.
When energy flows through this somehow, for reasons we don't fully understand, it feels like something.
Emotions, energy in motion, subjective experiences of feeling inspired and doing good, or feeling terrible, wanting to die.
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.
Everything we do in neuroimaging right the EEG or 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 epigenome because of metabolites and whatever intermediates are there.
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What I think has been missing in this whole landscape of health frankly, has been somebody who understands the different levels of analysis.
Uh uh.
Great neuroscientist now at NYU once told me that a real intellectual of which you are is somebody that understands and can communicate something at multiple levels of granularity.
That's very, very important.
So I'm very reassured by everything I'm hearing and where this is taking us.
That takes us to your opening question, which is like takes us through mitochondria and how that affects cellular and organ and behaviors.
I think what we just touched on here is like mitochondria flowing, transforming energy.
And then that energy kind of ripples out at the level of the cell.
And there are metabolites that mitochondria are producing.
Based on the energetic state of the mitochondria.
There'll be more acetyl-CoA and citrate, and lactate and alpha-ketoglutarate.
And those are all molecular imprints of an energetic state.
And then those molecules carry this energetic signature that's in the mitochondria to the nucleus and then boom, they get written down as the epigenome.
And now the cell?
All 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 mitochondria.
And then that ripples out.
Now the cell experiences its environment in a certain way energetically.
It starts in the mitochondria, ripples out to the nucleus.
Now the nucleus is able to make proteins like cytokines.
And so cytokines in many ways are signatures of an underlying energetic state.
So what we call inflammation, my understanding of inflammation is it's an energetic state.
And in many cases, if the energy doesn't flow freely or with low resistance in the system.
If you're a cell and either you're running out of oxygen, you're hypoxic, electrons can't flow.
As a cell, you have this primal experience of what you experienced earlier.
You're not breathing.
You're like, I have to take a breath or I'm going to die.
So if you're a cell and you experience a version of this, a really primal version of this, you need to do something.
So you call out.
You call out.
You call out for help.
That's where the cytokines come in.
Yeah.
Cytokines are universal language of cell-cell communication.
Cytokines are not immune.
There's this fundamental way that cells have to talk to each other.
Assuming that it is this repeating set of principles of energetic flow.
Let's get a little woo for a moment.
Let's get really woo for a moment.
We are in California.
Because I am beginning to understand it's grounded in real biology.
For instance, people have heard of the 27 Club.
There's this – it's not a club anyone wants to be a part of which are incredible musicians and artists who just seem to have this incredible – talent and intensity, and they die at 27.
And 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, you know.
Jim Morrison, and Jimi Hendrix, and Janis Joplin, and there are others.
I don't know if they're all in the 27 Club, but I believe so.
And there are others.
But this idea that for people whose quote unquote, flame burns, really hot their intensity, 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 that subdue people.
These are drugs that energize people.
Yes.
And it's as if really there was a lot more life packed into a shorter period of time.
And they die early.
In a parallel vein, I once had a conversation with someone that I understood was a child prodigy.
And he stopped me at one point and he said, no, former child prodigy.
And I thought, okay, we're being kind of detailed here.
But I went and started reading about child prodigies.
You know, you don't meet many adults that are brilliant, who continue to get brilliant their entire life, more and more and more and more brilliant.
In other words, child prodigies eventually plateau.
They just get there a little earlier.
And in some cases, a lot earlier.
Have you ever heard of somebody graduating medical school at 16 and then becoming the best physician in their field, continuing into their 70s and 80s?
No, people caught up.
People catch up to prodigies.
And so there's this idea perhaps, that You know the allocation of energy.
When it's really directed in time and in space to certain circuits of the body, we see incredible feats.
I'm like, whoa.
But then it doesn't continue forever.
And I'm going to bring this around to this concept of longevity in a moment, but I'd love your thoughts on that.
And then I'd like to talk about how the things that all of us can do can keep our mitochondrial reservoir high enough so that we can allocate it in different directions.
But just curious your thoughts about people who 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 doctor who's 16, or the person who graduated law school took the bar at 17 or something.
Then you look later and they're doing interesting things, but they're not phenomenal later in life.
People caught up.
There's a parallel in biology, which is how different species develop much faster.
Then they reach reproductive age much faster, and then they die much earlier.
Like mice, for example.
They live like two to three years, and they develop really quickly.
So everything is accelerated.
And there's two beautiful papers one published in Nature, one published in Science on the same month, in 2023, that I think shed some light on this.
They ask, what controls the pace of development? in mice and in humans.
And so they took mouse cells, human cells, stem cells, put them in a dish, and then you look for 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 an organism that develops, grows and dies in like 80-ish years have very different developmental rates.
And then they ask, what's different between that?
What controls the pace of development?
And they found that the main driver of this.
And then they did experiments where you can accelerate or decelerate the pace of development by modulating mitochondrial metabolism.
And when you say mitochondrial metabolism, is it fair to go back to the analogy of the Morse code thing where the animals that develop quickly and die earlier?
It's like a faster transformation of energy.
Exactly.
And that was regulated by NAD.
I think a few people who listen to this know about NAD, and So NAD seems to be kind of a dial on the rate at which energy is transformed.
So interesting.
Long ago I was getting frustrated because all the discussions in the longevity space were failing to acknowledge – I'm a developmental neurobiologist first – that development is the most rapid period of aging ever.
Look at a kid at one versus three.
That's a lot of aging.
And we don't think of it as aging because they haven't peaked in terms of their vitality and their maturation yet.
Look at somebody before and after puberty.
First of all, completely different organism of any species, right?
Person, different personality.
Much more, but 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.
If you look at the rate at which people acquire secondary sex characteristics going through puberty, typically they acquire one or several all at one stage, and then it continues.
How long the acquisition of secondary sex characteristics carries on essentially is a measure of the duration of puberty, because it reflects a bunch of changes in the hypothalamus.
We know that.
And that it cascade out to the body hormones and so forth.
I knew kids in junior high school who we went away for a summer.
He came back and there was a kid on my soccer team.
I'm like, that's a grown man.
Like he had a beard.
But I won't mention who this is.
And he was very like muscular and lean.
And he would score like nine goals every time he went to the more advanced soccer league and stuff.
I saw him in my 30s.
And I was like wow, he is.
And there was no envy or upset about this, you know, or schadenfreude or anything.
I really like him as a person.
I was like, well, he looks like he's like 45.
He had aged much more.
And then I knew other people that had, they kind of matured more slowly.
And sure, lifestyle factors play in here.
But they were developing in a way as adults where you're like wow, they really like taking great care of themselves.
But speaks to this idea?
First of all, that maybe the rate which one moves through puberty is predictive of lifespan, plus or minus some lifestyle factors.
So what are your thoughts on that?
Is it conceivable?
I think it's conceivable.
And there's nice data on energy expenditure.
How much energy is the body burning to go through whatever it's going through?
And again, nothing in biology is free.
That's kind of one of the basic energetic laws of life.
Everything costs energy.
And in development, you see when babies are born, they're a little hypometabolic.
They don't burn as much energy as like an adult per, you know, kilogram or pound of body weight.
But then within like a year, you see this massive increase in energy expenditure.
And then it kind of peaks around five years of age when kids are like developing so quickly.
My son is six years old and he's learning so much, changing all the time.
So energy expenditure is like... peaks around this time.
And then by 10, 15 years old, it's around back down.
And then by 21-ish, it's adult.
And then it's a flat line for the rest of adulthood.
Then around like 70 years old, you start to see this decline.
Yeah, it's a myth that metabolism slows as we age.
I mean, it's true that if we don't keep our muscles and movement et cetera, breathing exercise, a lot of it is just breathing.
Bringing oxygen to your mitochondria.
Well, as a friend who's in incredible shape once told me, I said, what's your workout regimen?
He's in his 60s.
He's just 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 you're trapped on a plane?
He's like, I breathe hard for an hour.
Former SEAL team guy, so they're a little extreme.
But, you know, he makes a good point.
But the idea is that we understand from this paper published in Science a few years ago that metabolism basal metabolism doesn't change much as we age.
We thought, oh, my metabolism slows.
It's not true.
Once you hit adulthood, once you hit your 20s, your metabolism is not changing much at 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 cellular level, they're- I'm referring to the basal caloric need.
How much energy you should consume to- Yeah.
Basal metabolic rate, like minus the running, the lifting, et cetera, that you do.
Now, of course, lifting can add muscle, which then raises your basal metabolic rate, but just this idea that oh, my metabolism is slowing as I age turns out to be completely false.
People have used that as an opportunity to write off.
They're overeating, they're over consuming energy in most cases.
We've developed a model called the energy conservation model, the brain-body energy conservation model of aging, the BEC model.
And so we could dive into this.
But I think there's significant changes that happen in some cells.
As cells age, they start to actually burn energy faster.
When cells become senescent, they burn energy faster.
And then they're sending signals.
I'm struggling, energetically speaking.
And that's what I think inflammation is.
You have some cells not all cells some cells in the body.
They're kind of over the edge, they're becoming senescent, and then they send signals.
And those signals are the same signal that we release during sickness behavior.
If your immune system is like really struggling energetically because it's trying to fight off a virus, it's gonna send those same cytokines.
And when those cytokines reach the brain, the brain says, oh shit.
We're going to go bankrupt.
You know, the energy budget is threatened here.
So let's save energy.
And then you become apathetic, 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 that 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 you can fight off inflammation.
Really what this is is you're bringing the organism's energy resistance, the cells that are struggling.
You're kind of normalizing them.
And then you don't feel like you're running out of energy.
So I think it's a perception problem.
So- i'm now going to imagine that one of the reasons why we have less energy in quotes uh, we feel as energy and we feel less energy, thank you as we age is because of inflammation in the body calling more energy to be allocated to those cells that are in the inflamed area, and they're consuming more energy.
So by reducing inflammation, you have more energy to allocate to other things.
Correct.
Got it.
And so this is very different than how we were talking about at the beginning.
When I said, you know, my advisor came up to me why do we have less energy?
I just imagined it was rundown of mitochondria.
So this is what creates a kind of dynamic tension.
And that's very practical for me and for everybody.
For instance, I could run more to increase the number of mitochondria in my body.
I can sleep a little bit more to offset the inflammation from the running, but ultimately I'm playing a game.
I have to budget.
Am I going to exercise more to get more mitochondria?
So my brain and body have more energy, but I'm also going to create some inflammation when I exercise and that's going to eat up a bunch of energy too.
So it's just like time or money or anything else.
You can't do everything.
So- you know, my mindset has always been and I think I'm going to stick with this frankly, lift weights three days a week.
Do cardio three days a week.
Rest completely one day a week.
Do the other things, like sauna and cold, as you see appropriate, but Make darn sure you're getting six to eight hours of sleep each night.
I've been pretty religious about that for a long time.
And try to not burn energy on drama or mind-numbing things.
And certainly don't use any substances that use up a lot of energy excessively.
I do drink a lot of caffeine but you know like prescription stimulants that I know people rely on a lot.
Like...
I'll just call it out, modafinil.
I've taken it once when sleep deprived.
You feel as if you slept eight hours, but you're borrowing that energy from someplace.
And it's not just the crash that happens later.
It's the long-term effects of this.
And I think this is why people who use amphetamines and cocaine and things like that stimulants we often find that sure they die of heart failure.
That's very common, actually, in people who use cocaine earlier.
We won't 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, et cetera.
But at some point, you're increasing inflammation that way as well.
Inflammation is a reframe that to me completely changed my perspective on what inflammation is.
Inflammation is an energetic signal.
If there are cytokines in your blood, it means somewhere in your body, and that's not true of like all cytokines, but the major cytokines that we think about, like IL-6 interleukin-6, it's secreted by muscles, not during the exercise.
Like you're doing your run, right?
Like I'd say you run intensely for an hour or two hours.
IL-6 doesn't increase.
It's when you stop exercising, boom, you get this beautiful spike of IL-6.
And then you ask, what is that?
So IL-6 is a cytokine, right?
It's a cellular signaling system.
And then IL-6 goes to your fat and then it says, we need energy.
Like lipolysis.
Chop out those lipids that's stored in your fat, release that in the blood, because the liver needs it to make glucose.
And then the IL-6 goes to the liver as well and then tells the liver make glucose because the muscle is depleted right.
And the IL-6 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.
So then the IL-6 then is a signal, right, to mobilize 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 recruits the fat.
It recruits the liver.
And then it sends signal to the brain.
The brain has IL-6 receptors as well.
And it says, you know, feel like crap.
Like, you need to recover.
Lose your vitality, your vigor, at least for a little bit.
Yep.
And rest.
And, like Arnold said, you become stronger, you make your mitochondria more mitochondria and you become fitter.
Not during the exercise, it's during the rest period.
So getting sleep, six to eight hours, definitely.
And about stimulants like caffeine and other stimulants.
What they do is they prevent you from feeling energetic stress.
So if energy is not flowing properly in your body and you should be sleeping to kind of decrease that energy resistance, then those stimulants kind of make you oblivious to those signals.
And now there are clinical trials, which I think are potentially dangerous, that are happening where –.
Those drugs are being developed antibody-based 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 it simplistically and you think the body is a molecular machine, you think here's what's happening when people are sick to have cancer.
Right?
GDF-15, just growth differentiation factor 15, which is a protein.
It's a cytokine.
It's secreted by cells when energy can't flow properly in mitochondria.
So if the cell is burning energy faster than it can sustain, it will start to secrete GDF-15.
So people with cancer who end up developing cachexia, right?
Their muscles... melt away, they tend to have very high GDF-15.
And then GDF-15 can go to the brain and, as far as we know, the only place or as far as 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.
GDF15 is made by every other organ in the body, including tumors.
So what happens is that people with very high GDF15 feel terrible.
And if you actually inject GDF15 into an animal to ask, what does it do?
Like, what does GDF15 mean if you have a lot of it in your blood?
Well, animals actually puke.
And it caused, you know, an aversive reaction.
Visceral malaise is the technical term.
So you feel like shit.
GDF-15, which is produced by cells struggling energetically anywhere in the body, signal to the brain and makes you feel like shit.
We know now also GDF-15 is the trigger for morning sickness in pregnancy.
So the reason, you know women, especially hyperemesis gravitarum HG, which is like terrible women who have this Many of them want to terminate their pregnancy.
It's so horrible.
If GDF-15 rises like 10,000-fold, there are not many hormones that can increase that much.
During pregnancy, the placenta sends out GDF-15, maybe to tell the mother like, chill out, reallocate your energy.
You're growing something that is costing a lot of energy.
So we know GDF-15 does this.
So now what pharmaceutical companies have tried to do is to say okay, let's block GDF-15 signaling so people don't feel like shit.
And so there's this one trial that was published in the New England Journal last year, and they show, as expected, if you block GDF-15 with a monoclonal antibody, people don't feel as terrible.
And they eat a little more, and they don't lose as much weight.
Right?
So it's basically if you're sick in a hospital, you have cancer, you're getting chemo, you don't want to eat.
And energetically.
I suspect this is the right thing to do, because you're saving 10 15 of your energy budget, reallocating it to healing processes, your immune system, whatever the body needs to survive that challenge.
Now you're kind of depriving the brain of that signal.
So people actually don't lose as much weight.
So then that trial said success.
If you look at the fine print and you look at the table where they report mortality, mortality was double in people who were receiving the drug.
That trial was not powered to detect mortality as a primary outcome.
It was powered to detect changes in body weight.
So that didn't end up being a main finding.
But if this is real... right?
You're preventing people from losing weight and they feel a little less nauseous, but there 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.
There's nothing normal about chemo conditions, but I think you understand what I mean.
That the body's intuition to not eat is smarter than any kind of you know molecular chicanery to overcome that signal and have you be hungry.
And you would think, oh, they're getting more nourishment.
I thought you were going to tell me that more of them lived.
You're telling me twice as many died.
Died.
And recently there's another trial, large-scale trial for heart failure that looked at this using this antibody to block because when the heart struggles, dilated cardiomyopathy or congestive heart failure.
Energetically, it's really demanding for the heart to be pushing against high blood pressure or to be failing right.
So there's an energetic stress in the heart at that point.
GDF-15 goes through the roof.
So now people know in cardiology, GDF-15 is a really good marker of heart failure.
And then the thinking.
I think our way of thinking energetically about GDF-15 is a little different than what the rest of, I think, the field thinks.
People see GDF-15 as a marker of inflammation.
And then maybe that's like immune or I think it's a marker of energetic stress.
The heart is calling out for help and trying to kind of calm down the rest of the system, right?
And by signaling onto the brain.
Turns out many more people developed heart failure and like adverse events under the drug.
So they stopped the trial.
Where you block GD15.
Yes.
So if you block-, This is the danger of molecular thinking of everything in terms of receptors and ligands, like the things that plug in.
People might not know.
Ligands are things that plug into receptors and activate them.
I mean, I love modern biology and medicine.
There's a lot of beautiful things, yes.
But the systemic effects are impossible to predict.
I guess that's why you run these trials.
I do have a question, as it relates to this, which is a big theme of your work, which is about stress.
Well, I'm sure people are wondering by now, tell us about the gray hair reversal.
So let's start with that.
Let's just get that out of our systems.
I will say, despite some theories, not that anyone cares that much.
I've never dyed my hair on my head.
I do have some grays, but the number of them waxes and wanes with how much sleep I'm getting.
It's kind of interesting. perhaps, but my beard's gray, right?
And I'll tell you, I'm not sure that all gray can be reversed by just reducing stress.
But I don't dye either my hair or my beard.
So I'm a natural experiment in this.
What's the deal?
Can people reverse the graying of their hair by reducing their stress?
Can people accelerate the graying of their hair by stressing more?
Likely both are true, yes.
Okay.
And I think what we discovered is that hair graying, at least temporarily, is reversible.
And this was surprising, because it goes against this notion that aging is a linear process that just happens over time, no matter what you do.
And here we should know, actually a hallmark of aging, which is depigmentation, losing color in your beard and your hair.
It's something that happens to almost everyone, but at different stages of life and so on.
And then on the same person, and the reason we got into this was that this felt like the perfect experiment.
Like you have every hair on your body is about 100,000 hairs on your head.
Every hair has the same genome.
They're all genetically identical twins.
And they're all exposed to the same exercise regime, the same food, the same stress levels.
Yet some hairs go gray when you're late 30s, and then some hairs go gray when you're in your 80s.
What the hell is happening?
I thought if we could figure this out, the basis for the heterogeneity, the hair-to-hair heterogeneity, maybe we can understand why different people age at different rates.
Because it's very clear that there's no more than 10 of how long you live.
That's genetically driven.
Like the best studies put this at around 7%.
7% of longevity is genetically inherited maybe, and then about 90% is not.
Is lifestyle factors.
Lifestyle, food, exposures, whatever is non-genetic.
People will take solace in those numbers.
Yeah, I think those are really powerful numbers.
And they surprised me because I had learned, you know, through my training education, that the majority of how long you live is, you know, your parents.
And I think this is legacy.
It's like dogma.
It's not science-based.
It's dogma from, you know, the Human Genome Project era.
Like through the 90s, we were hoping we would find the gene for cancer, the gene for heart failure, the gene for Alzheimer's, the gene for schizophrenia.
And then the human genome was sequenced, 2001.
And then there was like 10, 20 years of GWAS genome-wide association studies trying to find people who have this disease and trying to find which gene do they have that other people don't have right.
Those large-scale studies.
And if the 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 hypothesis was wrong.
It was a useful hypothesis, like many hypotheses are.
It led us to learn a bunch.
And the human genome, the sequencing that was such a driver of progress in biomedical science.
But it's failed to solve the big mysteries about why we get sick, when we get sick.
No genes will tell you this.
You know, I would say the Human Genome Project, like so many things, the brain connectome proteomes inflammatomes,
Necessary, 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.
I know this because I 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 it's great.
But
The information you get is necessary, but it's not conclusive of anything.
But it is good work.
Yeah, it's good.
Of course, it's good.
There's a lot of really high-quality science that's happening.
But I think in general, academic science has kind of lost track with its core purpose.
And now we have like an incentive system and there's a lot of forces at play in administrative processes that don't serve the primary end goal.
Well, it's all getting revised now.
It's – for better or worse, it's all getting revised.
So I see your point.
I'm warmed by the fact that, even though my parents are still alive and are doing well, thank goodness, that only 7 percent of longevity is – dictated by the genes.
So if you have parents that lived a long time, this also means you got to keep upkeep is important.
But what you do is is key.
So so with respect to the graying hair isn't the most important problem.
People can dye their hair right if they want to.
People can shave their head if they're losing hair.
There are a bunch of ways around this monumental problem of graying hair, but I think what it illustrates is really interesting.
That there's plasticity.
Yeah.
So could you explain the result?
So when we started to think about this, we thought what if we found hairs that have like the same hair has two colors?
So you have a piece 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 of your hair used to be inside the body.
It's a bit like tree rings.
If you cut down a tree and you look at the tree rings, you can basically go back in time and say ooh, 20 years ago there was a fire here.
And then 45 years ago, there was a drought.
And the tree rings look different.
Yeah.
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.
Stressed, relaxed, good relationship, bad relationship.
Yeah.
And hairs grow.
Writing a grant after the grant.
Yeah, yeah.
That was actually part of the data for that study.
I was one of the participants early on because we became interested in this.
We found hair that were two colors.
The tip was dark and then the root was white.
And then we thought, oh, if we can 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.
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?
So that was the idea.
And then back then my partner went to the bathroom and then she brought back.
She had very long hair.
And then you could see clearly the same hair, two different colors.
It's like, shit, aging.
Hair graying, there's plasticity here.
And then we found hairs where the hair was white and it went back to being dark.
And 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 and then their root was dark.
And then there was a segment, two centimeters, but like almost an inch of white.
And then the rest of the hair was dark again.
What happened in that two centimeters?
Did she share?
Yeah, exactly.
So that became the question.
So then we developed, we said, okay, we need to do this quantitatively.
She didn't tell you what had happened?
No, no, no.
We were collecting hairs in Ziploc bags.
So now people started to mail us, you know, Ziploc bags with hair.
And we got some hairs from France, hairs from Canada, from different places in the US, across body regions in South Asian, African American, you know, white areas.
So, it was clearly real.
And then we thought we need to develop an objective semi-quantitative method to quantify stress.
Because we quantify now, we bought a scanner, you know, old style like photo digitization system.
So we bought one of those high-end scanners and then we could iron out like a single hair, tape it down and then like scan at super high resolution.
So then we can get like a digital picture 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 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 we could go back in time with this, and then I sat down with this participant and said okay, This is now and this is a year ago.
And then you can look at your calendar.
What was the most stressful part of the past year?
And then for her, it was very clear.
And then what was the least stressful part of the last year?
And then people would rate this.
The y-axis is most stressful at the top, the least stressful zero at the bottom.
And then they put points and then connect the dots with the line.
So then you end up with a line graph of someone's recall of their stress levels, anchored in some objective life events.
So that was the methodology we use.
And for her, she had sent us the hair a few months ago.
And then we were doing the interview.
And her profile was so beautiful.
And she said, I submitted my thesis.
She just graduated her PhD at Stanford, actually.
And then she you know, had a chill summer and everything was okay.
Then she had some issues with her boyfriend and they broke up and then she was like in crisis.
What do I do with my life?
Do I, you know, get this job or that job?
She had to go to Europe for some family issues.
And then, And then she ended up moving to New York City, getting a job, reconnecting with her boyfriend, and then life was great.
And her graph looked exactly like this.
And that period lasted two months.
And it mapped to the gray zone.
It mapped surprisingly perfectly with the graying, right, where the hair lost color.
So it was the stress peaked for two months and then came back down.
She said these were the most stressful two months of my life super interesting and that the paper's got a lot of press, as it should be.
I've received about 300 emails since that paper was published.
People from sending me pictures from all over the world saying like, I found this two colored hair.
I thought I was crazy.
Google this and found your paper.
When I was growing up, my dad told me that he had a cousin who worried so much that he went to bed one night and woke up and all his hair was on the pillow.
And I didn't know until I was an adult that that story was designed to get me to stress less and that it wasn't completely true.
But that's hair loss, not graying.
Is there any graying of hair, beard hair or head hair, that is just simply related to age?
Or can we say that any graying of hair that's age-associated is likely to be associated with the increased inflammation that comes with aging, aka stress, a different kind of stress, not psychological stress.
Yeah, maybe it depends how we define stress.
We define stress as anything that costs energy.
Well, inflammation costs energy.
Inflammation costs energy.
And making a cytokine costs energy.
And if you're a cell and you have a receptor for a cytokine and the cytokine docks, the ligand docks, that's going to cost energy.
It occurred to me that when based on what you've told us that when we're young, we need a lot of energy
And we don't want kids to overeat, but they need energy.
And their levels of inflammation are very low.
Kind of a perfect situation for development.
As we get older, we generally move a bit less or a lot less.
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, not more, as a rule.
Okay, but there are always exceptions to that rule. but there's a lot more inflammation.
So we're actually much more energetically expensive because of inflammation as we age.
And I'd be willing to bet that some of the graying of hair is related to the aging inflammation thing.
I mean my level of stress.
Who knows what it is, because it's been, you know, jagged line for so many years.
I don't know what baseline is.
I drink caffeine.
Like, you know, like most people, we're masking a lot of the things that are going on.
But I love the results showing that increased stress grays hairs and reducing stress ungrays hairs.
It's a correlation.
It's a correlation, but it's a really cool result.
I want to talk about restoration and recovery of energy.
Maybe with 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 when this one hair goes gray and then it recovers its color.
What's happening energetically?
So we took a single hair and chopped it into pieces and did proteomics.
You have to, because you're a molecular biologist, right?
And I mean, mitochondria is our way to tap into the biology of energy.
So then we thought maybe there's something there.
And initially, I didn't think there was mitochondria in the hair.
It turns out every hair that we walk around with is loaded with mitochondrial DNA.
And, you know, forensic, if you find a hair on a crime scene, you can figure out who is there.
The DNA that gets sequenced is not the nuclear genome.
It's a mitochondrial genome.
Really?
Because hairs have a very high concentration of mitochondrial DNA.
So you guys, you can't commit a crime and expect to get away with it, because if you leave one hair, Martin's lab is going to sequence it.
We don't do forensics.
Sure, you don't.
What 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 did not expect that.
And we repeated those experiments in two different proteomics core.
And the proteomics core hated that experiment because hair is like notoriously it's full of keratin, those super high abundance proteins.
And then they mask every other signal.
But we were able to kind of get good resolution data for other non-keratin, non-hair proteins.
And three mitochondrial proteins were consistently upregulated.
There was more of the mitochondrial energy transformation machinery in the gray hair compared to the dark hair.
Love the direction of that result.
I don't love that stress increases graying, but I love the direction of that result because it's yet another brick on the wall of what you're telling us that Stress is an energy requirement.
Inflammation associated with aging is an energy requirement.
Being sick creates different energy requirements.
And we need to obey these different energy requirements.
Fascinating.
So, in terms of removing or reducing metabolic demand, in order to keep our system going first, of course, is sleep.
Right.
You were telling me earlier, before we started recording, that during sleep, how much does our metabolic needs become reduced?
Decrease.
Yeah.
Most people know, when you sleep, your heart rate goes down and a bunch of your body temperature goes down, and that allows us to stay alive with 10 15 lower energy expenditure.
And they're different between different people, but 10 15 is kind of an average of how much energy you're saving by sleeping.
And there's a theory of why does every animal need to sleep?
And if you sleep deprive a mouse or a rat or an animal, They die eventually.
And we know from severe cases of mania and bipolar disease.
People can die from going without sleep for multiple days.
And that might be one hypothesis because sleep saves or conserves energy.
And if you don't go into that state of torpor, almost like mini hibernation, then somehow the organism can't sustain that.
And we have some thoughts as to why this is.
I was reading recently about this glymphatic clearance of waste in the brain that occurs during sleep.
And there was an interesting figure in this paper showing that every mammal puts its head down during sleep.
And there's some cute pictures of pandas sleeping on their side.
The giraffe apparently puts the top of its head down in order to presumably, increase glymphatic 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 when we want to rest our body and our mind.
And, with the exception of rapid eye movement, sleep when the brain is very active, sort of a reboot, of sorts periodic reboot.
Sleep just seems like this beautiful way to allow the mitochondria to either restore or you.
Just you don't want to, you can't out eat sleep deprivation either.
You can't eat more to get more energy.
That's very clear.
Yeah.
That's a very important statement.
Yeah.
Now I've long been curious about things that people can do in order to either reduce their sleep need, or I prefer to refer to it as increasing their vitality while waking.
And it is true.
There are data showing that people who meditate for an hour or so per day, or two 20-minute sessions seems to be the most typically used protocol can fairly dramatically reduce their sleep need and really go from like an eight-hour need to a six-hour need with a 40-minute investment of meditation.
What are the data on how meditation reduces mitochondrial function and energy use?
I want to start by saying we don't know what mitochondria do when we sleep.
Like do mitochondria sleep?
You lose consciousness and the body, you know, goes into this hypometabolic restorative state.
And yes, there's glymphatics and you know – garbage clear out in the brain, which I suspect might have an energetic effect.
If you have garbage in your 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 where we had people come in the lab for 24 hours, sleep into the lab, and Evan Cholson, a student in my lab, is analyzing those data.
And I think for the first time we'll be able to know what do mitochondria do when you fall asleep and you go into this hypometabolic state and you're kind of conserving energy.
How is energy reallocated?
So we see sleep as a two-arm mechanism. process, one, it slows some things down.
If the heart beats 10 times less per minute, that's a lot of energy.
Every time the heart contracts, systole, diastole, both contraction and 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 we suspect that there's three main buckets of energy expenses that the body needs to sustain at some point in time.
One is vital.
You need to keep your heart beating at your resting heart rate, the brain function, your kidney.
You need to be detoxifying, clearing the blood and all of your vital organs.
That's vital cost.
Second is stress cost.
If your sympathetic nervous system is activated because you're worrying about the future or worrying about the past, or you're stressing yourself out, this costs energy.
And then your blood pressure increases, that costs energy.
Heart rate increases, costs energy.
You're sweating a little bit, costs energy.
Your hair rises.
Anything that 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.
And those GMR processes happen at the level of organs.
When you have an organ that gets bigger and stronger, for example after weightlifting, it can happen at the level of a cell.
If the cell needs to repair its membrane, needs to repair its DNA, this would be growth maintenance and repairing.
If you make more mitochondria, mitochondrial biogenesis, after a workout, that would be growth, maintenance and repair.
And because there's a finite energy budget, there's an economy of energy.
How much energy you have needs to be distributed between those vital costs, the stress costs and the GMR growth maintenance, repair costs.
So if you're stressing out all the time, we suspect this actually steals energy away from GMR.
And then you're not healing, you're not growing, you're not learning maybe.
And what sleep might do is actually shut down all of those stress processes.
When you sleep, heart rate variability increases, right?
Parasympathetic tone increases.
Sympathetic nervous system goes very quiet.
And then all of the stress-related expenses increase, then become quiet, then that piece of the energy budget can be allocated to growth, maintenance and repair.
And when you meditate and there's this beautiful study that shows expert meditators can go into 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.
Meditating, it seems, and some trained people can bring energy expenditure down by 40%.
This is more than sleep.
So they're able to shut down or quiet down maybe vital processes.
Like we know the heart rate can go down extremely low.
Probably stress processes.
We know this from measurements and meditators.
And then maybe that energy can be reallocated to growth, maintenance, and repair.
So if you do more of GMR in your waking life because you live more mindfully and you don't stress yourself out, think about the future or the past or self-related thoughts, then maybe you can do more GMR during meditation or during your daily life.
And then you don't need as much sleep if the purpose of sleep is to reallocate energy towards growth, maintenance and repair.
It's definitely been my experience.
I've talked before on the podcast.
I'm a big fan of yoga nidra or I coined a variation on it non-sleep deep rest.
It essentially consists of lying down intentionally, staying awake for 10 to 30 minutes, and you do a progressive bodily relaxation while keeping your mind awake.
The reason it's useful is twofold.
One, you emerge from it with a ton of energy, mental and physical energy.
Your vigor is restored, even 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 create a sleep inertia.
You feel sleepy afterwards, then people drink caffeine and then That can cause issues or just even make it harder to fall and stay asleep at night after naps.
Whereas non-sleep, deep rest, yoga nidra is very, very efficient this way.
The other thing is that I've been playing with lately that I've found to be tremendously useful.
I sort of joke about this.
I was telling my girlfriend the other day, like...
We'll just say for the hour or so before sleep, to just like listen to music, have the lights dim, just like really relax.
Or maybe the 30 minutes before sleep, just really relax.
And it's almost as if I mean you're 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 slowing of the heart rate before sleep.
I suspect that's what it is because it's not actual sleep.
So you think it helps you get into deeper state of sleep faster or?
I think it's restorative in its own right.
And it probably helps sleep as well because it's anti-stress.
And so, you know, it's hard to tease those apart.
Yeah.
But I think this idea of not just lowering the lights, dimming the lights, but also reducing the heart rate as you head into, you know, getting ready for sleep, you know, brushing your teeth, getting ready for sleep, you know, and pre-sleep activities, being very relaxing.
We hear that for the de-stress component, but I suspect that the brain is already going into a sleep-like state.
Yeah, so I suspect that's accurate.
And if you're... creating that environment, and then it allows you to relax.
What relaxing means basically is you decrease the energetic cost of sustaining your organism, then lowering heart rate, lowering cortisol in your blood norepinephrine, catecholamines and the things that cost a lot of energy.
We've done experiments in cells in a dish.
You give cells glucocorticoids, like a cortisol mimetic or norepinephrine.
And then we wanted to know how much energy does it cost to mount a stress response?
Those hormones are not damaging by themselves.
But if you give them to cells, those cells go into a whole choreographed evolutionary ingrained response that prepares them for the future.
It's called allostasis.
And that costs a bunch of energy.
And we found it was about 60%.
So this doesn't happen in human beings.
But if your energetic metabolic rate increased by 60 with glucocorticoids, you'd be in big trouble.
So it might not be as much in the whole body, but we know now that just a stress hormone on cells in a dish human cells is able to increase the energetic cost of life.
So it costs energy to worry about stuff.
So if you can decrease the level of those hormones and decrease the level of cytokines in your blood inflammation, that's going to save energy.
And then, yes, maybe sleep is more restorative.
And the sleep study we did.
There are people whose sleep energy expenditure drops significantly, like 20.
Other people doesn't drop almost at all.
In particular, people whose mitochondria don't work very well.
So we've been so fortunate to work with patients and I'm not a physician, but I'm in the clinic half day a week and I see patients that I've followed now for about six years who have genetic mitochondrial diseases.
So they're pretty rare, but they have a mutation or a 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.
They don't feel well.
They avoid exercise at all costs because it just feels so terrible, because 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.
The best biomarker of mitochondrial disease is actually GDF-15, which tells us something about what GDF-15 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.
And if you do a sleep study on those individuals and you look at how well do they decrease their energy expenditure to go into this restorative state, the parasympathetic nervous system can't kick in.
So some of the biggest difference we see between mitochondrial disease and people who have normal, healthy spectrum of mitochondria is this inability to slow down and to go into this restorative state at night.
So that positions, mitochondria in the context of restoration and our ability to heal and lifespan in those people has 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, we should talk about nutrition and exercise and supplements, dare I say, and prescription drugs, including the GLPs.
I realize you're not a nutrition expert, but you think about energy.
You can't out-eat a bad night's sleep, but we all need nutrition.
When you personally step back from all the noise around nutrition.
What are the key takeaways for you in terms of how you think about optimizing your mitochondrial health and energy flow?
Yeah, I think we've gotten things wrong for two main reasons.
One is we don't think about the individual.
We try to find... one size fit all solutions.
Carnivore is good, or keto is good, or high carb is good, or meat is bad, or all of these variations which people feel really strongly about.
And this brings us back to the value of the human experience.
You know for yourself.
If you change your diet and it changes your life like you have vitality you haven't had in like 20 years and your symptoms inflammation, right is gone and you have clarity of mind you've never had.
I've met several people now who've had this kind of life-changing energetic shift happen when they go on a ketogenic diet and when they install intermittent fasting.
Life-changing shit.
Yeah.
So they know that this is real, right?
And then you do an RCT.
Randomized control trial.
Yeah, thank you.
You do a randomized clinical trial.
And then what you do there is you feed everyone the same thing ketogenic diet or standard Mediterranean diet or whatever 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, let's say, 50 people here, 50 people here.
And then you ask, did the ketogenic diet improve mental health?
Or did it reduce inflammation?
Or did it do that?
And then often in RCTs for dietary interventions or drugs, what you find is Not really.
Maybe a little bit, right?
And then if the study was adequately powered and there's like an 8 shift in your primary outcome, then it becomes P less than 005.
The P value, the statistical value here becomes significant.
And now you say, ooh, the ketogenic diet is effective for this.
Or the ketogenic diet does not work for X.
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 amazing responders.
There are people whose lives was changed, truly.
And then there are people who didn't change anything.
And then there are also people who got worse.
And then you average everyone.
You squish everyone into this average.
And then the RCT is a statistical test of averages.
Nobody is the average.
Nobody is actually the average.
Literally.
Literally.
And then the ketogenic diet could literally save lives and it could cure or be like a really solid treatment for schizophrenia or bipolar or Crohn's disease or whatever it is for like 20 of the population.
And we'll never find out just because we have a science of averages.
Yeah.
Well, a safe self-experimentation is the only solution to that.
Yeah.
It's the only solution.
Yeah.
And there's a clash here between the value of the human experience, right?
You know that this thing works for you and that you live at a higher level, right?
You can fulfill your potential.
And then you see the science, you know the capital S science that tells you no, what you think works, doesn't work.
And they just, no, but it works for me.
And then you have a white coat wearing person who says, no, no, I have the authority.
I can tell you this RCT shows that it's not effective.
And I think this really... is damaging.
It makes me angry.
I feel uncomfortable when I talk about this because this is completely disregarding the human experience and service of this framework that doesn't serve the individual.
The RCT was invented for very good reasons.
It's very useful in some circumstances, like do antibiotics work?
Should you be doing surgery this way or that way?
But when you get to interventions or treatments that are likely to have a highly individualized response and there are people who respond amazingly to this, to that then you end up disempowering people.
So I think there's a clash of, I know this to be true from my experience.
And then I have this person in this position of authority, the scientist or this doctor, that says no, this doesn't work, because the RCT showed that it didn't work.
Like this is really, this breaks trust.
And so I understand the frustration of so many people who've lost confidence in science and the medical establishment I think for good reasons in many cases.
Is it fair to say that then there is no best diet for mitochondria except the one that's energetically not excessive, not calorically excessive.
Yeah.
So eating too much for sure damages the whole system, including mitochondria.
So the first piece of response to your question is because we don't think about diet in an individualized way, we're missing the boat on actually finding diets that work for different people.
So we're working on a platform that would empower people to get some objective readout of energetically.
How are they doing?
And then a framework also to we can all be thinking scientifically about our own health and about ourselves.
And once you realize you are, the flow of energy rushes through your body with different levels of resistance.
Then you can think about the food you put in your body is actually fueling that flow.
You are the movement of energy and that is continuously fueled by what you put in there, by the activity you do and the kind of things you engage with.
So yes, we need a framework for this.
We're working on that.
So that's the individualized piece, right?
There's very.
At this point I'm pretty convinced there's no one diet that is the best diet for everyone.
I've seen people thrive on very different diets, since we've been kind of working on related areas.
And a few years ago I received a research prize, the Bazooki Prize in Science, which was so enabling
And Bazooki Group is a family foundation whose son was diagnosed with bipolar disease and tried all sorts of treatments and drugs that didn't work very well or actually made things worse.
And so they were on a diagnostic odyssey and trying to find something for years.
And then finally, they came across a psychiatrist who was using the ketogenic diet as a treatment.
And so he went on a ketogenic diet.
And Jan Buzuki, the mom, said, like, I had my son back.
Like within a few weeks, his mood got stabilized.
He was able to sleep.
And he stopped kind of cycling between mania and depression.
So for him, that really worked.
And so I was sensitized to that area of work and research and then dozens of other patients.
And I've met so many people now who – who manage their mental health disorder with ketogenic diet.
And they test their blood ketones to make sure they're still in ketosis.
And there's now a continuous ketone monitor, CKM, CGM.
So you can test your ketones.
I wore one for a month and learned some really interesting things about my body and about you.
Know how Were you ketogenic?
I tried.
Did you like it being in keto?
Ketosis?
I really enjoyed the state of ketosis.
And...
And I think there's a reason why fasting is a common practice in every ancient tradition.
And every religion has a fasting component to them.
It puts the organism in this pro-healing state, which is probably why you don't eat if you're sick and why animals also stop eating when they're unwell.
So it seems to foster, promote something.
And then I had much better clarity of mind.
And that's what a lot of patients report as well.
Did you stay on it?
No.
It's hard to maintain.
It's hard to maintain, and I didn't feel the need.
I missed berries.
I know I don't handle sugar well, so I ditched refined sugars maybe like 20 years ago.
Do you drink alcohol?
I don't.
There's good research.
When I saw that study, I was like, oh, my God.
This might be why I feel like shit the next day after I have alcohol or my sleep is not good, and why patients with mitochondrial disease the majority of them are very alcohol intolerant.
And then you can make all sorts of theories about.
Maybe it's like the detoxification enzyme in the liver.
Energetically, dirt on edge, right?
And then if you look at how much energy does it cost to get rid of the alcohol, right?
It's a toxin.
So everything in biology costs energy.
Nothing is free.
A basic energetic law of life.
So if you put alcohol in the body now, the body has to spend a precious portion of its energy budget to removing alcohol.
And it disrupts your sleep.
The data came out recently.
This was covered in the traditional press.
I think you can look it up, folks.
There's something like a 50% reduction in alcohol 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.
And there was a.
You know the argument has been made by me, but others now as well, that zero is better than any.
And the upper limit for sustained health, before you start to run into some issues, is probably one or two drinks per week.
But this idea that wine is good for us.
There's been a reanalysis of that by Keith Humphries and others at Stanford.
If you look at the way those studies were designed, and he's coming on the podcast, so I'm not going to detail it now.
The way those studies were designed was poor experimental 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.
Are you willing to sacrifice 10% of your energy budget going towards alcohol detoxification?
Can you spare that at 10%?
If you care about that 10% and you want your vitality, then maybe you don't drink.
When I was going to a lot of scientific meetings.
There's a lot of drinking that happens at scientific meetings.
I would take solace in the fact that A, I'm going to sleep relatively early.
11 o'clock isn't that 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, bigger labs.
And I was like, I'm going to take your lunch.
I'm going to take your lunch.
The competitive edge.
Yeah that, and I'd recommend that they watch certain Netflix series, because that'll definitely take your competition out.
No, I would watch people who are in the field of health and science degrade their health in real time.
And it was perplexing to me because the amount of alcohol consumption.
Anyway, I'm editorializing now.
It's bad for your mitochondria is what I'm getting.
I think it steals a piece of your energy budget.
Oh.
So whether you want to allocate that energy, if you have extra energy to spare, you want to do that.
That's a good way to think about it.
In some cases, let's say vital processes, nothing you can do about this.
And as you age, probably those increases.
Stress processes.
Mm-hmm.
The mind creates most of those, stress-related energetic costs.
And then growth, maintenance, and repair.
If you're, for some reason, circumstantial or you have some, we all have shit from our past that we deal with, if this is burning a big chunk of your energy budget every day, You're a little traumatized or 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?
You're maybe wasting, let's say, 10% of your budget to detoxifying alcohol.
But if you're relieving that stress, I suspect this is why –
There are people that really like their social drinking because it relieves kind of a stress, energy wastage.
Yeah.
No, it makes sense.
Yeah.
No, the stress piece is huge.
And when you – you've set up this framework for us, which I really, really like about – energetic flow as opposed to just energy coming into the system as a key thing to think about and then how we allocate energy at the mitochondrial level but at the decision-making subjective whole whole person level um doing things that bring us a sense of meaning clearly is energy building not just energy expending although we can't take it so far that we're not getting enough sleep i mean you know there's always the the housekeeping that needs to be done of sleep and nutrition etc i am curious about exercise You mentioned training for a marathon will double the number of mitochondria.
At most, yes.
But where's the sort of sweet spot of doing more exercise in order to increase mitochondrial density and et cetera?
Efficiency, but not so much that you're robbing mitochondria from other areas of your biology that are critical.
Uh-huh.
Yeah, good question.
If you exercise too much and you're a young, healthy male, you can actually decrease testosterone level.
Endurance training can shut down your testosterone production, your reproductive system, basically.
So the kind of trade-offs we talked about with young females also applies to males in those kind of ways.
Where that threshold is, I think, is also highly individualized.
Overtraining syndrome is a very real thing.
Even people who devote a lot of their life and energy to becoming better athletes, there's a limit.
I used to be a competitive cyclist and I raced semi-professionally in my college days.
Uh, and I knew that if I worked out, if I was on the road and I used to do like intense and long distance workouts, if I was like, I logged all of my training, you know how many hours kilometers, all of this?
Uh, if I did more than like 20, 22 hours a week, uh, on the bike, I would get like Achilles tendon.
That was kind of my sweet spot, um, or my sensitive, you know, week, um, spot or my knee.
So there was a limit, right?
And for me, that limit was 20, 22 hours.
And maybe that's why I never became a professional cyclist.
I wanted to at some point.
I thought maybe after undergrad, I'll be a 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?
And I did some plyometrics and some other, you know, sprint building exercises.
And I weighed like 10, 15 more pounds than I do now.
I was investing more resources there.
Then, when I started a PhD, I was more inspired to you know.
At some point it was like okay, do I write this paper or do I go for a three hour bike ride?
And then spend like three hour recovering.
You know making a great amount of food, and So the trade-offs.
At some point I started to feel like I want to put my energy towards, you know, developing these ideas.
And so there was kind of a trade-off from athletic performance, you know, and muscle building, towards more intellectual activities.
And that sweet spot I think is unique to each person.
And some people I think use running as a – as like a therapy.
Some people use eating, some people use running, some people use gambling.
You know, whatever it is for you.
So I don't know that there's kind of a number of hours, number of miles per week, for sure not.
And whether you do something you know that inspires you, or whether you do something and it's a fucking grind like I think that makes a difference for how much energy you have to do it and how much is good for you.
I know you spent a lot of time in the gym.
Steven Pressfield, who you chatted to, and his concept of resistance.
I think that there's something there.
You need to give the body a certain amount of resistance.
And that's true physically, but also true mentally.
Too much resistance crushes you, right?
And then it's like too difficult and it's demoralizing and de-energizing.
But not enough resistance is not inspiring.
And then being bored, like being in prison, that might be why being in prison is so –
It's a thing we do to people who've done really bad things, because it really crushes a human spirit when you have nothing to do.
Having something to do is kind of exerting resistance to the human mind.
So 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 worth underscoring it again, because we've established, you've established let's be fair here you've established that it's not just about mitochondria making ATP and energy, actually controlling energy flow.
Transforming it.
Transforming it, all of the Morse code rate 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.
Yes.
You know that that and that's where the transformation occurs.
And so perhaps the the whole concept of getting more vital, getting better, learning, et cetera.
It's about that feeling of friction.
Yes.
When I've done episodes about neuroplasticity, I've tried to really get into people's minds.
Like the moment you feel agitation, that means the opportunity for plasticity is turning on.
Your brain doesn't change if it's in a state like any other state.
This is unfortunately, why traumatic experiences are so good at rewiring the brain because your brain goes.
I'm not used to this much agitation, adrenaline and norepinephrine.
Something whatever's happening now is really important.
And it actually grabs too much.
And that's PTSD.
It grabs random events.
It's a whole thing.
But for healthy learning, adaptive learning, you have to have the resistance.
If you can do the thing, your brain won't change.
If you can do the thing, your body won't change.
And I try and explain this in the context of cognitive stuff that agitation and frustration, like you had to seek that out.
You don't want to overdo it.
But I think if I wish they had told me that when I was in school.
I know.
Right.
I mean, I was a pretty avid learner, but it's like you just want to tell people the moment you're frustrated.
Awesome.
Like your circuits are primed to change.
Yeah.
Yeah.
Anyway, I get very impassioned about this.
Yeah, me too.
Because it's how we get better.
Yeah.
And I think most people feel that and they think, oh, they're doing something wrong.
But actually the errors signal that more and tell your brain you have to change.
Yeah.
Yeah.
It's just that the change takes time.
And it takes time and it takes energy.
Like the reason change is difficult transitions.
Any kind of, you know, moving house is one of the most stressful things, you know, that –
Like, you know, getting divorced or changing relationships, any kind of transition.
By definition, a transition requires change, which requires energy.
And I suspect the reason why life transitions are difficult is because they cost energy.
And we have a finite amount of it.
So resistance...
The energy resistance principle is something that we've developed recently with Neurotia that encapsulates this.
It says life is resistance.
You cannot have life if there's no resistance.
There's no transformation.
You're the cadaver.
Yes, exactly.
Or you're like a beaming light ray in outer space.
That just goes on.
It just goes on, goes on, never transformed.
There's a potential for change, but there's no transformation.
It's never going to change until it hits resistance, a green leaf on Earth, for example.
I love it.
It's such an important concept.
And just to refer, I think you think about bodybuilding or working out how the body gets stronger.
The way the body gets stronger is by facing resistance.
If your muscles get accustomed to a certain weight.
If you want to grow in strength or in mass, you need to go heavier.
And so it's increasing resistance.
Same thing if you send in astronauts in outer space, their body gets so weak.
Their bones demineralize, and their muscles atrophy, and their hearts weaken.
And then they come back onto Earth, And then they struggle.
And that's because when you go out in outer space, there's no resistance, right?
The gravity is, you don't feel gravity because you're constantly falling, right, in orbit.
And then there's nothing resisting the structure of your body.
They age very fast.
Yeah, exactly.
Astronauts don't fare well.
No.
Now they have ways to compensate for this.
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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, et cetera.
The ones that come to mind are the following, just to constrain it a bit because it's a huge space.
Coenzyme Q10, a number of people, including me, take.
This isn't a plug for it.
It's just I take it.
I was told that it can help my mitochondria.
I don't take methylene blue.
I'll mention why in a moment.
There are some peptides like SS31.
It's becoming very popular now.
Cocktails of NADSS31.
Things like this.
Oh, yeah.
People are injecting this stuff like crazy.
Oh, yeah.
SS31?
I guarantee within a radius of one mile.
There are a lot of SS31 injected.
We're in Los Angeles.
Oh, yeah.
SS31.
Yeah.
In cocktail with NAD, it's very common.
There are a couple others, SLU, there's another one.
All of this is MOTC.
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 answer.
Yeah, the term mitochondrial function, mitochondrial dysfunction, I think are misnomers, because mitochondria have many functions.
And so I think that the nomenclature, that's more of maybe a researcher kind of niche kind of thing.
But I think it's misleading to talk of mitochondrial dysfunction, because mitochondria transform energy and make ATP, but they make hormones and they make signals.
But to your point about supplements, I was a student when SS31 was discovered.
And I remember the person who discovered, Hazel Settle, who discovered SS31.
She was presenting at meetings and I've seen now it was commercialized as stealth peptide and then it went on the publicly traded
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.
Those things, we're trying to tweak the system.
I think what we're trying to do with supplements is to optimize, tweak the circuitry, the metabolic circuitry that we have for flowing electrons to oxygen.
In an ideal world And electrons flow from food to oxygen like two poles of a battery, like a simple circuit with just the right amount of resistance.
Too much resistance, and then it feels terrible.
It feels like if you hold your breath and you feel like you're going to die.
That's too much resistance.
Not enough resistance feels like you're unhinged, and probably we think that's what mania is, where you feel like there's so much energy that you can't contain it and then you can't sleep and then you can't.
Your life kind of falls apart.
ADHD is another good example of that.
That might be.
So maybe those kind of conditions, disorders of the mind, we think are disorders of energy resistance.
We don't have direct evidence for most of it, but I think that's a fairly well-supported idea.
And supplements in cases when your circuitry is impaired, If you're deficient in coenzyme Q10.
If you take it, you're going to feel it.
And if you're deficient in something like vitamin B12.
There are many parts of mitochondria that require B vitamins to flow electrons towards oxygen.
So vitamin B deficiency, different vitamin Bs, including NAD, can really be terrible.
And people have chronic fatigue-like syndromes from vitamin B12 deficiency, for example.
So in cases where there's a deficiency or you think there might be a deficiency, maybe supplements can help palliate those.
My sense is...
You know, we've evolved over very long periods of time and we're really well optimized.
And the body and the mind are as two expressions of this energy flow kind of can work harmoniously together if we bring awareness to it.
And if we keep energy flowing through exercise, we're not eating too much, and 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 lives. healthy, fulfilling lives.
And they get sick once in a while, but they recover without supplements and without medical intervention.
So I think there's a path to get there.
And so I think there's a place for supplements, but I've never taken a supplement.
And you have plenty of energy.
I cultivate my energy in different ways.
And I feel like it's a better investment of my energy and my research group.
We haven't studied drugs and we've been solicited to help pharmaceutical companies or other supplement type to test the effects of supplements and mitochondria.
If we go in that route, then I think it's one approach that might lead useful results at some point.
But I feel like my energy, my contribution as a scientist is better position and understanding the energetic basis of mind, subjective experiences body, and developing a more holistic system for what we are 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.
And I should just say, for sake of being responsible folks, don't inject peptides that are for quote unquote research purposes only.
People are getting them on the gray market.
I mentioned methylene blue, so I should just close the hatch on that one that I've avoided it for two reasons.
One, I saw the images of blue brains from people who had recently taken it.
Doesn't mean their brain stayed blue because they had taken it recently.
There are some data that point to the fact that methylene blue can intercalate into dna and possibly cause some mutations there.
That worries me, and there are some data as well and chris masterjohn talked about this recently that if people are mitochondrial damaged, deficient dealing with carbon monoxide poisoning, other metabolic issues, that perhaps methylene blue, because it can reroute some of the pathways for these electrons, can be helpful.
But if people are generally healthy, that it can cause more problems than it solves.
And that was enough for me to just say, I'm going to just stay away from this stuff.
Also, I don't want to have a blue tongue like a monitor lizard.
Anyway, that's not a serious thing, but it just seems a little shaky for me and I do worry about people just taking it.
And I'm very happy that your laboratory is focusing on the molecular aspects but also, as you said, the experiential aspects.
Meditation, meaning purpose.
And this notion of flow is something that I want to just ask you about.
When you see things like Tai Chi, if you're in New York City, if you see people early in the morning, if you get up you see them doing Tai Chi, or
Years ago, I saw an interview with Iggy Pop, you know, as a musician from like the 70s.
And he's like in tremendously good shape now and has always been.
And they asked him, like, what's your secret?
They always ask these kind of like, what do you eat kind of things.
And he was like, it's all in the Qigong breathing.
And I chuckled because Tai Chi, Qigong breathing.
I personally believe that, whether or not it's running Tai Chi Qigong, breathing or lifting weights, the activity itself has certain benefits related to respiration, blood flow, muscle stress, et cetera, and recovery.
But that the additional layer of benefit comes from the understanding over time yoga as well, the understanding over time of how to direct energy in your body and mind to be able to force yourself to get through some hard repetitions but then to rest completely in the rest period, to dynamically move from one position to another, not just as a physical movement but as an exercise in being able to anticipate.
Okay, here comes the painful part.
I'm 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 meta-learning that comes from just having done it over and over.
So you have this expectation and understanding.
You're learning how to allocate energy.
And I just like your thoughts about this.
So I don't think it's Qigong per se, Tai Chi per se, yoga, Pilates per se, lifting weights per se.
I think those have each different benefits.
But what are your thoughts about learning to be a better?
Oh gosh, this sounds super woo, but what the heck?
Energy channeler.
Two scientists talking about energy channeling.
Well, this is not woo.
I mean, the mitochondria flow energy.
You can say they're channeled for energy flow from biochemistry to electricity, to ATP, to metabolites, to reactive oxygen species.
All of these are different forms or, you know, modalities of energy.
Is there like a molecular reality to qigong or to qi or to, you know, prana or, right?
Like maybe.
And maybe if we look at all of these practices and we ask, what's the point of consilience?
What's true?
Maybe they all have a little piece of the truth.
Molecular biology and 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 contain both our molecular, physical existence and our experiential existence.
Existence the emotions, the states of consciousness, states of mind that we know are real, crazy states of consciousness that we can experience with psychedelics, for example.
What can encapsulate all of this?
What's the bigger truth?
And I think the bigger truth is that we are energy.
And we flow through this channel, this body, right?
We have mouth, we have nose, lungs, heart.
All of this you can understand, or anatomy.
Human anatomy you can understand as 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.
Instead of electricity flowing through, we flow food.
And then oxygen is at the other end pulling on electrons.
So maybe all those practices have something to do with 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 image this with an MRI, maybe not yet.
But I suspect there's a truth there, and maybe one piece of that truth, and that's the way you describe Tai Chi and the way we do exercise.
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 grow or evolve.
Mentally, we need resistance.
So think about energy resistance brings us to think there's a philosophy of education that could be built around this.
The art of education is finding the right amount of resistance to expose a child to.
If the problem is too hard or you're too severe, you're going to crush them.
You kill 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 just a sweet spot.
That's what great masters, great mentors are able to do.
I've started to see my role as a mentor for people in the lab like this a little bit.
I see them as energetic processes.
They're transforming energy.
They need the right amount of resistance and not too much.
And it brings me more compassion maybe for them as energetic movements.
And then I realize I'm more sensitive to the effect I have on them.
But all of this movement and the Tai Chi, the exercise, lifting and resting, is analogous to what the heart does.
The way that the heart works is by contracting systole and then by relaxing.
And then contracting and relaxing.
Same thing for the way neurons work.
Boom, action potential, refractory phase.
You need to add that period of science, right?
Boom, action potential and refractory.
Same thing with sleep-wake cycles.
You need to get awake.
Your body temperature rises.
Cortisol spikes up.
You're aware of the world.
You're exposed to stressors.
If there's not enough stressors, slash challenges, slash meaningful things in your life.
You get bored and you want to die.
So you need that, but then you need to kind of let go and sleep, right?
So sleep-wake 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 and then the sun sets.
It's same movement as sunrise, sunset, you know, day, night is contraction, you know, resting, yoga.
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're ready to body by bringing so much resistance into it so that you can finally relax.
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 art of being.
Because if we do too much doing I think many professionals know this if you're always in a doing doing, doing and you're never kind of sitting back and resting and just being And being really means just flowing, to use verbs.
Being is just having your energy flow and it's doing its thing and it's healing.
It's healing the body and consolidating memories and everything, all the beautiful things that happen during sleep.
As opposed to transforming it into something in the outside world, like a paper or investing.
And it's the balance.
Clearly, what I'm hearing and I don't want to speak for you, but what I'm hearing is that so much of health mental health and physical health and life really is about states of mind and body and mastering the transitions into and through and out of those states, but in a controlled way, learning to direct those so that we're not at the whim of.
I mean, this is the challenge that we get pulled into, the drama or the numbing out of some online activity or the you know the energy of something going on over there that really pulls us, you know.
And so I think we have to have that self-awareness.
But I love the idea that resistance itself is the thing to seek, not as a permanent state, but as a temporary state that you can then move through.
So, and I think if...
Clearly people learned a ton today, but if nothing else, they now understand the biophysical principle that it's through that resistance that you direct and create energy for something else.
Transform.
You transform.
Yes.
Exactly.
Thank you.
Good managers know this.
If you want to have fulfilled employees and a team that really derives joy and purpose.
People need to grow and learn.
And the way that happens is by creating the right amount of resistance.
And Steven Pressfield said this 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.
And he talked about how when you feel afraid of something, right?
Like as an artist.
I think he speaks, you know, as an artist and for artists like you – you feel into this problem, or this challenge, or this new project.
And you're like, oh, I don't know.
This is scary shit.
Well, I think his advice was when you feel fear, this is the signal that there's something there for you, that this can help you grow.
And I resonate with this and I make a lot of my decisions.
I can think rationally and think logically about steps in a biochemical pathway and about logically in five years and 10 years doing strategic planning.
But I have an increasing sense that when you make decisions with your heart and basically this is by listening to your energetic state you feel you see something.
You see someone you're like ooh, I like this, or this is a little scary right.
I started to ask my wife, and she's really good at this, how do you feel?
I think I used to ask my partner, what are you thinking?
And if you ask someone, what are you thinking?
Like right away, you go into this like cognitive level which is really devoid of, like the beautiful movement of energy.
If you ask someone, how are you feeling?
And then if that person, if you can you help, you create a space for that person to really answer from that place, then you actually get to, you know, tune in to their energetic state.
And then you can be, I think, much better partner if you see a relationship as an energetic state.
And then I can be in a better state if I know that, oh, she's not feeling great.
And then I think the more you cultivate this kind of energetic awareness, I agree.
Awareness, personal awareness and, I would say, energetic awareness, feeling into your mitochondria.
Maybe that's what it boils down to, I think, is our greatest superpower as human beings.
And that's not a new concept.
It's, I think, the foundation for a lot of spiritual traditions, like cultivating awareness of self.
And then you realize at some point there is no self.
I'm this movement of energy, and then you movement of energy, and then we're all arising, emerging from an underlying current of consciousness and their ideas about this.
I'm not sure how it all fully gels together, but awareness also as a scientist.
If you move through science without self-awareness, then your biases end up ruling the projects you take on, end up ruling the grants you apply to and end up ruling the kind of science you produce and you generate.
So, without self-awareness, I think we're not always fulfilling our potential, and fulfilling our collective potential as humanity.
If we can be the best person that we can be, then we can help other beings being their best self.
We can be present.
And when you're present to someone, it's basically saying I see you energetic process and I'm opening to you.
How are you feeling?
That's why I think those kind of conversations and connecting deeply with another human being is so rewarding.
And that's true, I think, across the board.
We're social creatures.
And what this means is we love connecting with other people.
And I suspect that's because it helps us flow.
It helps us, you know, our energy flow.
And then we love projects that are stimulating, you know, inspiring.
And what those words mean, stimulating, inspiring, they're all like energetic terms.
So the things that helps us flow, being like cognitive or spiritual or, you know...
Intellectual, social.
All of those I think probably boil down to is this thing helping energy flow through my mitochondria more easily, or is it bringing me resistance?
Or is this thing bringing me resistance, that I feel I have the capacity, the inner potential to push through and then, when I let go, then I become stronger and I grow as a person and I learn.
I love it.
It's a mitochondrial or energy flow centric view of everything.
And I think it is the basis of life.
I know you're working on a book now.
It sounds like there's also another book to follow that one, The Mitochondrial Marriage.
At some point,
I'm only half kidding.
What you described is really beautiful and it captures so much of what people are seeking.
And I think what people understand intuitively about the things that make them feel good versus the things that make them feel bad and the we have to pin above that, that resistance is critical to growth.
So it's not just about things that don't take effort versus things that take effort.
So it's it's not.
It's not as simple as that.
It's uh, it's not infinitely complicated, but it's not as simple as that.
Speaking of of uh Solutions.
Before I came in here to talk with you, I solicited the internet for some questions.
We sometimes do a, not rapid fire, but brief answer Q&A.
So, if I may, I'm going to go fetch my phone and gather a couple of questions to ask for some short answers.
First question is why is it that over-consuming calories causes disruption to the mitochondrial pathways?
Yeah, I think it's because it increases energy resistance.
It's like a simple electrical circuit, maybe a computer, and then you're cranking up the voltage.
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 blood lipids.
And so the effect this has?
We understand it.
It pushes electrons onto your poor mitochondria, mitochondria evolved to be super sensitive.
And then when there's like a bit, not enough energy, they change their behavior.
If there's too much energy, they change their behaviors.
They're chronically too much energy pushing on them.
If you do the, we have a little equation that helps us think energetically about this, called the energy resistance principle ERP.
And this says if you raise the concentration of glucose you raise the energy potential like the voltage equivalent.
And then that increases energy resistance.
If you're not flowing that energy, if you're not moving, being active, stimulated by something, you just put too much food in the system.
It increases the resistance to energy flow.
And then you start to have more dissipative losses like too much reactive oxygen species and too much damage.
Molecular damage can happen.
That's probably why overeating and why diabetes and why metabolic diseases increases the rate of aging and increases the rate of all sorts of 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, and or measurement.
So the measurement piece, we're working on this.
Anna Monzel in our group said, who's moving to Germany now, is developing a mitotyping platform.
If you're a scientist or not and you want to explore the molecular differences between mitochondria and different organs of the body, you can go to mitotypeexplorerorg.
And then explore the different mitochondria and different organs.
Tissue, organ specific mitochondrial optimization I think mostly is going to be driven by the organ or tissue specific use and flow of energy in that tissue.
Like we were talking about earlier, if you train on something you train on playing the violin, parts of your brain are going to be more activated.
Specific circuits are going to be activated together.
They're going to wire together and then make more mitochondria most likely and probably become more efficient as well.
So there's rewiring at that level.
So I think mitochondria follow or are there to serve the flow of energy.
So if you flow more energy in your legs, you're going to make more mitochondria to kind of increase the number of flow channels.
Mitochondria has little channels to flow energy towards oxygen.
So yeah, I don't know that we have ways yet, maybe with light therapy, photobiomodulation or maybe electromagnetic field.
At some point.
We need to be developing as healing science unfolds and we understand ourselves energetically.
I think we need energy-based or energy-informed approaches to help organisms heal, and probably those are going to target mitochondria.
Yeah.
Yeah, using light or other tools to direct healing of 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 advanced meditators can increase blood flow in like one part of the brain.
Yeah.
There might be unsuspected ways of tapping into using the mind basically to direct energy in different ways.
I've started to see the mind as a master regulator controller of energy.
The mind can literally depolarize your muscles and then cause you to run.
It starts up here with the mind, the inspiration or the motivation to contract your muscles or to run or to do any behavior.
This is like the mind controlling the energy flow in your muscles and then making more mitochondria as a result.
What are the best or most sensitive tests for mitochondrial health, if any exist?
And I will say a number of questions, and there were many, many questions centered around this idea of how can I measure mitochondrial health as a patient or with my physician.
Are there any companies that make good mitochondrial health tests?
There are diagnostic tests that clinics offer somewhere and those are good to diagnose mitochondrial diseases.
There's a few companies that have popped up because this is the future.
Thinking about ourselves energetically, realizing we are energy.
Yeah.
If that's true, which I think it is, then what do you do about this?
And 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.
That really is what moves us into action and... determines whether our lives is worth living.
Those things haven't been brought together.
And we haven't also explored scientifically the healing process.
So we're developing an institute that will work, do the research to develop those technologies and then we'll do the work as well to bring those into, into technologies that can reach people and you know people can have in their homes or maybe as a wearable or right as a kit that you get at home to really help you tune into your energy and know what works for you, which diet, which supplement or which you know there might be.
You know it might be that this person in your life, when you're with them 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.
So we're working on initiatives and new methods to tune into mitochondrial health.
I don't know now of things that I would use to tap into the health of our mitochondria.
I can attest to both the pro-mitochondrial health and anti-mitochondrial health of certain relationships.
What are some small daily tweaks that can help increase?
And people said energy, but let's just use that as a proxy for energy flow.
Like if you could give just one, two, or three recommendations.
There are a lot of busy people in this question list.
They're saying, I've got kids, I've got a busy job.
One, two or three things that are straightforward, outside the typical exercise get your sleep, et cetera.
What are some tweaks, dare I say hacks?
I think trying not to eat in the morning, like skipping breakfast, seems like it does a lot of well for a lot of people.
And I've heard for a long time breakfast is the most important meal of the day.
My dad used to say that.
He still believes that.
And I think it's hurting his health now in his 60s.
So I think trying to be hungry once in a while is probably a good thing.
And then when you feel that hunger and then you're reflexively reaching for food, I think you're probably doing something good for your mitochondria.
Your mitochondria when you're hungry or when a cell.
What we know that the science is, If a cell is hungry in the dish, the mitochondria start to fuse and there's more kind of the social connection between your mitochondria.
So maybe it happens inside the body, and then you get rid of the bad mitochondria.
You make more new ones that work better, more efficient.
So being hungry once in a while is probably a good thing.
And then being out of breath.
You mentioned one of your friends, I think, who says like I just need to be out of breath for an hour.
Right. finding ways to be out of breath.
That can be like a run.
It can be being at a gym.
You know whatever makes you breathe harder?
You breathe harder because your mitochondria are calling for oxygen.
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.
I need to say something about meditation.
I think somehow meditation does something to our energy that is valuable.
And just yesterday there was a piece published in Nature Reviews Cardiology, about transcendental meditation.
I think that shows that the world is changing.
You know, a clinical medical journal like Nature Reviews Cardiology is saying maybe there's something about like calming down the body, right?
And not only is this like calming down the mind, sure, like maybe it improves well-being.
This could actually be a treatment to help the heart recover right and to help treat a very serious, life-threatening disease cardiovascular disease.
I suspect there's something about meditation.
I have a 10-minute every morning.
I sit down and say, I'm religious about this.
I wake up.
First thing I do is sit down for 10 minutes with Sam Harris' Waking Up app.
It just helps me connect with my energy.
Then I think 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 mentally but probably also physically.
Awesome.
There's a lot of discussion about peptides.
MOTC, humanin, SS31, also called elamapretide.
Did you know that?
GHKU copper and various BPC157, TB500 analogs.
I told you, this stuff's getting popular.
People are curious.
Let me ask you this.
I'll jump in on their question because we talked about some of this earlier.
Would you inject any of these things?
I wouldn't.
Would you let your sibling mom or dad inject these things?
No.
There were many questions centered around the fact that fertility doctors OBGYNs, are recommending various things to improve mitochondrial health for sake of fertility and egg quality.
And this makes sense because the mitochondrial genes are involved in this spindle and the formation of the embryo, et cetera.
And the questions were specifically about the recommendations of ubiquinol and CoQ10 urolithin A.
These are very prominent 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 therefore egg quality?
There's some good data on urolithin A that improves quality in cultured cells and then in animals.
So it's possible.
And I think I saw recently some very compelling data on sperm mitochondrial DNA content.
Mitochondrial DNA content, like per sperm linked to infertility.
So I suspect that this massive crash, which is really worrying, infertility we're well below replacement right now.
We're having very few babies as a society.
It could be that part of the issue behind this is mitochondria aren't as optimal as they should be, or energy is not flowing as freely as it should be.
So I don't know about whether those treatments could solve the issue.
My sense is, the issue behind infertility 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 asked whether there is any evidence animal studies, in vitro or even in humans that electromagnetic fields can disrupt mitochondrial flow.
This is, I realize, somewhat of a barbed wire topic, because it immediately gets us to the place where people think oh, they're worried about 5G and Bluetooth and things like that.
I don't know.
I did an episode on fertility where I reviewed a meta analysis of data showing that indeed, sperm motility can be impacted.
But what are the data on EMFs or other electrical signals or other energy fields that could potentially impact brain sperm eggs?
If there is something in most cells that could respond to electromagnetic fields, I think it would be mitochondria.
If you reason about this from first principles,
In the mitochondria there's a bunch of iron, iron sulfur clusters which, some of them at least, are paramagnetic, meaning they interact with magnetic fields.
So I think, in terms of biological plausibility, I think there's basis to believe that mitochondria could be sensitive and respond and be functionally impacted by some magnetic fields.
So that's for biological plausibility.
Data.
I know some data where people have measured mitochondrial respiration, 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.
And it seems like there's an effect on this one function of mitochondria, which is respiration.
So there seems to be data that says this could happen.
What we're talking about in terms of magnetic field.
There is not 5G and it's not some Wi-Fi widely used magnetic fields or electromagnetic radiation.
They're pretty specific.
And the Earth's magnetic field, which is in very low level, seems to perhaps have an effect also on mitochondria.
And there are biophysicists, like my wife, Nerosha Murgan, who has done experiments with pattern magnetic fields, which is 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.
Back to the Morse code analogy.
You can deliver information through that and it seems we have preliminary data that shows the mitochondria might be changing.
In response to this,
Basically, you're beaming energy at a certain pattern.
Instead of with molecules like glucose and pyruvate, and lipids and stuff or light, now you're beaming energy in another modality, as electromagnetic waves.
There are proteins clearly and iron-sulfur clusters that can be sensitive to that.
I think there's some biological plausibility.
There's evidence that this might happen and affect mitochondrial respiration.
There's, I think, another layer of sophistication that tells us this potentially could be harnessed eventually to help rewrite some energetic states in the body.
Maybe we can use those at some point to promote the healing process.
Love it.
We'll see.
We will see.
Dr. Martin Picard, thank you so much.
You gave us a master class in mitochondria, mitochondrial function.
You clarified a lot of what is clearly confusion for people out there, including many biologists, mind you about how mitochondrial work and the spectacular things that they do.
The way you frame this whole notion of 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 game of sorts 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...
You're reversing graying of hair.
You're giving people agency over that.
And I just want to reemphasize 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 biophysical mechanisms.
It's really spectacular.
You're truly an N of one, as we say.
And I'm very excited for what you're putting together in terms of this scientific institute to solve healing.
Your book, we'll talk again later at some point about your book.
And I should probably also sit down and have a conversation with your wife, because she's got some spectacular results in this realm too.
She does.
Just thank you.
Thank you, thank you for the education and the actionable items that you're providing.
Thanks for coming out all this way.
Very grateful to you.
Thank you.
Thank you, Andrew.
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