#419: A Mind-Blowing Mitochondria Episode— Mito Transplant, Rare Diseases & Biomarkers With Dr. Natalie Yivgi-Ohana

Welcome to Longevity. I'm your host, Natalie Nidom. I'm a nutritionist, a human potential

and epigenetic coach, and I created this podcast to bring you the latest ways to take control

of your health and longevity. We cover it all from new technology and ancestral health

practices, to personalized interventions, and a very special interest of mine, peptides

and bio-regulators. Enjoy the show. Welcome back. I'm Natalie Nidom, your host, and I have

to share a secret with you guys. After I recorded this episode, my mind was so blown, I actually

had to take a break. I had to step away. I had to reboot my brain. It was like literally

blew my mind. And this is such an incredible topic. And the truth is that I have this incredible

privilege of speaking with world-class experts across every corner of Longevity. And every

so often, a conversation comes along that just truly expands the way I see how human health

is going to be impacted by some of this new technology that is as old as humanity itself.

So this is exactly what happened with today's guest, and I literally couldn't wait to share

this episode with you. Dr. Natalie Yivki-Ohanna brings an extraordinary depth of knowledge on

mitochondria, those incredible little organelles, breaking down how these tiny powerhouses

influence fertility, hormone production, immune function, and even the aging process itself.

We also explored the emerging science of mitochondrial transfer, and what this could mean for the

future of Longevity medicine. And they're already applying it to areas like neuro-degenerative disease,

fertility, rare diseases. It's really like, you guys are going to love this because I know you

guys, and I know you're going to love this. Let's dive in. There are some good tools in Longevity.

They're powerful, but quite impractical for daily life. Ozone therapy is one of these. The

research is compelling, but most people aren't going to clinics multiple times a week or setting

that equipment at home. And honestly, you shouldn't need to. That's why I was so curious when

wizard science is launched Oracle. It's their first ozonated oil in a capsule designed to be used

daily. No machines, no appointments, just a simple addition to a routine that's already working.

What makes it so interesting is its delivery. Oracle uses an acid-protected capsule,

so the ozonated oil reaches the small intestine intact. That matters because ozone doesn't work

like a typical antioxidant. It acts as a signal, encouraging your body to increase its own

antioxidant production, support immune balance, and improve cellular communication. And because

it's delivered through the gut, you're supporting the system where immunity, detoxification,

and energy regulation all begin. If you're looking for a smarter, more practical way to support

resilience at the cellular level, you can learn more about Oracle at wizard-sciences.com.

And make sure to use code NAT15 for 15% off your purchase.

Most people think magnesium is just for sleep, but what they're really missing is have magnesium

supports so many systems, including your muscles, your mood, and your stress response.

Magnesium breakthrough stands out because it combines seven highly absorbable forms of magnesium,

not one or two filler versions that don't do much. People tell me they feel calmer at night,

less twitchy or restless, fewer cramps, better recovery, and deeper sleep, all from one simple

nightly habit. And unlike most supplements, this one uses its delivery system designed to help

magnesium actually reach your cells where it can do its job. If you've tried magnesium before

and thought, I guess this just doesn't work for me, this one might just change your mind.

You can say 15% at bioptimizers.com forward slash bio NAT and use code bio NAT for 15% off any order.

Look, it's not about knocking yourself out, it's about supporting your body in the way it was

designed to work. Welcome to the show, Dr. Natalie Yiggy Ohana. It is such an honor to have you

here. And thank you for taking the time to speak with me today. Thank you so much. It's a pleasure

to be here. Believe me, a lot of people are going to be excited about this, including me.

So we're going to talk about the tiniest little structure in the human body, I think, or one of them,

it's not the tiniest because it's got tiny things inside of it. But the mitochondria, what we

talk about the powerhouse of the cell, which I think it's such a hot topic and has been in many

ways gets reduced to less than what it is. But this is your career. This is what you've built your

career around. So when did you decide that mitochondria was going to be your topic? I think

mitochondria actually decided I'm going to meet you. I'm completely controlled by these

organelles and fascinated. And it took a while. I mean, I started as an embryologist, so I'm an

expert in in vitro fertilization. And I started to study the role of mitochondria and embryonic

development. And I was fascinated by the fact that actually mitochondria are only inherited by

the mother. And then if we do an in vitro fertilization where we inject the sperm with the mitochondria

into the old site, eventually no leftovers of this mitochondria out there. It's only maternal

and it is selecting against the paternal mitochondria. So that's like it's enormous. And there is a

huge responsibility for us women to transfer this mitochondria to the next generations. I have

four daughters, so they will transfer my mitochondria. That's incredible because and I mean,

obviously we know that the ovaries are so dense in mitochondria. Yes, right? Which makes sense

on the fertility side. Yeah, very important because there are so many supportive cells and tissues

within the ovary to make that one special all size every month to fertilize. And also when we

go through first the puberty and then the menopause stage, what is the role of the ovaries and the

hormone production in might end the mitochondria aspects of it. So when I started my PhD, I was walking

actually an oil reproductive organ systems and mitochondria. And the fourth role of mitochondria

that I learned about is of course energy production. We'll talk about it greatly in a minute,

but they were all of mitochondria in steroid hormone production. I don't know if you know,

but the first hormone that is produced is produced in the mitochondria. And I studied a protein,

the transfer cholesterol from the outside of the mitochondria into the mitochondria,

where an enzyme converts this cholesterol to pergnenolone. Pergnenolone is now the precursor

of steroid hormone production, all sex hormones. I mean, all glucocorticoid and mineralocorticoid

and the sex hormones, all of them start in a process in the mitochondria. And when mitochondria

dysfunction, of course, you get distracted hormone synthesis. So it's super critical. There is no

life without all these hormones, of course, in the production of hormones by the mitochondria.

And there is no use in living, right, without sex hormones and what it does to our bodies and to

well, to everything. Well, I mean, look, you've just blown my mind and I'm sure a few others,

like cholesterol is used in the mitochondria. Like all these people, like this race to the bottom

on cholesterol as we age, which ultimately could be, I mean, I don't know for sure, but and I'm not

saying, but which could ultimately be feeding into the pathways that lead to the aging process

and decline, not to say we have to run around with high cholesterol, but an important role for

cholesterol, both in building our membranes, of course, and of course, we could drafts that are

important with cholesterol inside them for signaling within the cells and outside the cells,

but also for this very important task of steroid hormone production. You cannot do that without

cholesterol. That's incredible. So was there a not-how moment when you decided that, you know,

when you're like, okay, okay, medicine is completely underestimating mitochondria,

I'm going to do something about it. Yes, so there were two or a half moments. One was I was doing

my PhD on this life creation with mitochondria and the fact that they produce energy and steroid

hormones and there is no life without them. And then I did my post-told fellowship on triggering

cell death through the mitochondria. So if a cell has a damaging response, mitochondria immediately,

they behave like these smart bombs and they release content that start and cell suicide mechanism

that is irreversible. And then that was the first aha moment. I said, life and death controlled

by the mitochondria. And that's where I should focus my next life on. That was the first aha moment,

really realizing how important they are. And then the second one came after I finished my

on my academic training and I decided there is such a huge and mechanized in the whole field

of mitochondrial dysfunction that the problem was that no one could really say whether someone

has a mitochondrial dysfunction or not because there were no methods to measure that. And then again,

we are all going to suffer a mitochondrial dysfunction as we age. So age as a kind of mitochondrial

dysfunction, I said, no one treats it today. There are no therapies to fix my mitochondrial dysfunction.

That's where I am going to spend my life on. And I said at home for like nine months, just thinking.

And I read all these books and all and I went back to the early days of how mitochondria

well identified. And there was the Lynn Margolis. Lynn Margolis was a great scientist. She was a

woman in the 1960s. She tried to publish her endosymbiotic theory, meaning, okay, so

tell us about it. Tell us about it. Projected her publication about the endosymbiotic theory

that we all know today. This is a consensus. Absolutely. My mitochondria used to be bacteria,

independent bacteria that entered into the cell during the evolutionary process. So one and a

half billion years ago, the cells started to develop. The nucleus wasn't there yet. It was just DNA

flying inside the cell. And now this bacteria enters into the cell. Usually when a bacteria affects

a cell, they will multiply until they'll kill the host and then they will live to infect another

cell and so on and so forth. In this case, mitochondria entered into that cell but they did not

multiply until infinity just a little bit. And then they actually became an independent part

of the cell. And they transitioned most of the DNA into the nucleus and maintained just the

portion of it within the mitochondria. Now they can no longer live independently. They have to

reside within the cell and this is the symbiosis. What the mitochondria did were actually

enabling the cell to survive in an oxygen-enriched environment, which is what we have here on earth,

right? It's an oxygen-enriched environment and before that oxygen was toxic to cells,

but now mitochondria consumed the oxygen and the nutrients and produced energy for the cell.

And this is not cheap. This is a chemical molecule that is required for everything that happens

in the cell. It's called ATP or a denosine-3-4-5. And this is a chemical molecule that is needed for

everything the cell is doing. Every pump, every enzyme, every protein formation, nucleotide

for oxygen, every DNA replication, everything requires this ATP and that's how life began.

And now there are creatures on this planet that consume oxygen for this energy thanks to the mitochondria

that we have residing within ourselves. My aha moment, the second one that I promised came when I

suddenly realized that actually mitochondria were very selfish. They behaved like a selfish gene.

They wanted to integrate their DNA into the nuclear DNA to protect it. And now the nucleus produces

most of the proteins for the mitochondria. And this is a perfect symbiosis. And this is why I love

it so much. My aha moment was, can we use mitochondria to fix diseases? Can I integrate mitochondria

from one cell type and apply it to another disease cells? Will they go in? Like they did

you an evolution? And that's it. That's how we know we have started. It was crazy. But I just had

to test it. And it was true. Wow. So what was that scientist name you said in the 1960s? And who

didn't publish her paper and who ended up? Was it a guy? So Lin Margolis was a scientist in the 1960s

and she suggested the fact that there were endosymbiosis happening between different species.

It is also the chloroplasts inside plant cells which are also evolutionary. They're used to be

also germs and the mitochondria in our living cells. So she suggested that there is a structure

that enforces these two species to come together in order to supplement a missing function.

That missing function was the use of oxygen. And the outcome was the creation of the energy,

the ATP. She tried to publish this in 15 different journals and she was rejected in the 16th time

that was accepted. And eventually it's a common practice for everyone. This is the endosymbiotic

theory. When you look at the mitochondria under the microscope, they look like bacteria.

They are devise of bacteria. They contain your own DNA just like bacteria. And their DNA is

circular, just like a bacterial DNA. So everything about them says that they're used to be bacteria.

They actually can replicate independently from the cells multiplying. They can just

they do the fusion and and mitochondria. And they're very independent within the cell.

Yeah, no, I love mitochondria. I think they're the cutest organelle personally.

It's a surprise you don't have a big poster on your wall. I have a mitochondria there,

but I have the wall over there, yes. I'm sure you do. You're going to have to get mitochondrial

jewelry instead. I have my bag. And I have a mitochondria jewelry, actually a very special stone

that was brought all the way from Africa, from Ethiopia. And then an artist created a mitochondria

foamy from that stone. I actually should have buried that one of my partners actually created

that jewelry foamy. It's beautiful. I will show it to you when you come to me.

So let's talk about how understanding this this endosymbiotic origin of mitochondria. How should

does that how should that affect how we think about chronic disease or should like does it come

into play in terms of how we're thinking about chronic disease? Because it's so interesting,

right? What you said earlier, that you know, you've got these incredible branches like fertility,

chronic disease and mitochondrial disease specifically, but just any chronic disease.

And then just the pure process of aging, right? But when we're talking about chronic diseases,

does this endosymbiotic origin of mitochondria have an impact on how we need to be thinking about

it? Of course. So the first thing, of course, the fact that they are consuming oxygen and using

the nutrients that we need to produce the energy, we need to be mindful for the quality and the

amount of oxygen that we are breathing, of course, and how important it is that. And it's not

wondered that when we are doing sports and when we're doing yoga and we're singing, we're just

loading our bodies with oxygen that makes us feel good. That feeling good is actually boosting

our mitochondria with energy and eventually that's the outcome. When we are feeling our mitochondria,

there are huge differences between if we are absorbing now carbohydrates, glucose, for example,

or if we are now feeding our mitochondria with free fatty acids, because you know that the number

of molecules of energy that you produce from a carbohydrate versus from a free fatty acid

is completely different. You can get up to three or four fold higher numbers of molecules

if you consume free fatty acids versus glucose. So I think the mindfulness of what will cause

our mitochondria to be more active or more efficient in energy production, this is supercritical.

And we do know, I mean, we all feel the drop of energy and the drop and the start of frailty as we

age, we know that in chronic diseases people feel weak, they are less active. So how do we know

that? This is mitochondrial dysfunction, eventually. We feel the lack of energy, we feel tired,

we feel exhausted. This is practically mitochondrial dysfunction. And why is it happening? Because

mitochondria carry, as I mentioned, their ancient DNA that came from their bacterial origin.

And that DNA is circular and exposed. It doesn't have the three-dimensional structure of our

nuclear DNA, with all the proteins that are protecting it. And it is very, very protected.

It wound up and it has to unwind to work. And there are systems to fix errors within our nuclear

DNA that doesn't exist in the mitochondrial DNA. So the fact that it is open, very sensitive and

for insults, from the environmental insults, and that there are no machineries to fix damages

in the DNA of the mitochondria. I'm going to pose it to be very, very prone to mutations in the mitochondria.

Now, each mitochondria have multiple copies of mitochondrial DNA. And in each cell you have many

mitochondria, so even more copies of mitochondrial DNA. And sometimes if it's just several of these

are mutated, you won't feel anything. But with time, the process, the natural process of selection

of the good mitochondria is harmed with the age. This is the micromancy. So it's going down.

And what you see is accumulation of damaged mitochondria within the cells. And those mutations

in the mitochondrial DNA accumulate more and more as we age. And those mutations are what's

causing us to produce less efficient energy and eventually, even more reactive oxygen species,

because of the non-efficiency of energy production. And that further circulates and increases the

damage within the cells, all eventually connected to mitochondria. And there it is. So that's the

origin of why chronic diseases eventually evolved from this DNA. It is so sensitive to...

It's so delicate. Yeah, it's interesting. And really speaks to anything we can do to, which we

can talk about later, what are the things people can do to support my topology, mitochondrial biogenesis,

like to... What are the things we can do to do that? But I want to go back to something that you

said earlier. And you talked about the difference in ATP production between glucose as a substrate

fuel versus free fatty acids and ketones. In that, and I don't know if you have... Do you have a

position in terms of whether people should follow more of a ketogenic diet in certain states,

or is this just... Or does this more speak to maintaining metabolic flexibility so that the body,

like the problem is most people live in sugar burning, 1900% of the time, right? Because they

taste good, they make us feel happy. And the worst part is when we get sick, we go there. Because it

makes us... It gives us... I mean, I've just gone through something. I can tell you, I've probably

eaten more carbs in the last month than I have in the last... When we are stressed, right? And we feel

bad. You want to... Well, because of the cortisol is high, my adrenals are taking a hit, you know,

like I feel like going keto right now might not be smart. But maybe that's a trick. Maybe I should

be thinking more on the keto side. And I'm just curious, and if you have an opinion in these

chronic diseases, or in these situations where the mitochondria is really impaired, is there an

argument there that says that either introducing the right exogenous ketones at the right time,

or maybe following a ketogenic diet might be... This might be a use case scenario for it.

Yeah, I think a ketogenic diet that's a very dramatic, a very drastic...

They're problematic, like they're not perfect. Yeah. And I think we should... But definitely,

I do believe in the concept of more free fatty acids versus carbohydrates. There is a very

simple explanation to that. This is why I'm so strongly believe in that. What happens is that when

we consume carbohydrates, our cells immediately, there is a huge responsibility to remove the glucose

from the blood, right? You cannot stay around. That's what we want. Once it goes into the cells,

it becomes a source of energy, okay? And then it will create ATP in a non-efficient way, but

through the glycolysis, you will actually get ATP produced. You'll get about nine molecules,

I think, of ATP. And then if it goes into the mitochondria, you will get 36 molecules of ATP.

If it goes through the mitochondria, if the pyrovert goes in. So the responsibility of removing

the glucose from the blood and now creating energy through the glucose is a huge. And if you consume

both free fatty acids and glucose in your diet, you know it in a hamburger, okay? With the

bun and the cheese and the burger itself. So you have it all mixed in. What the cell will do,

it will use the carbohydrates for energy production. And the fat will go being sold because they don't

need it now. They have enough energy from the carbohydrates. If you eliminate the carbohydrates

from your diet, now you are educating yourselves that they need to use the free fatty acids in order

to produce the energy. The cell will multiply the mitochondria to the amount needed to face the

flow of free fatty acids that you are now consuming. And then they will not be stored. What happens is

you are currently, when you start a paleo or a keto diet, you are educating yourself,

now, to increase the content of mitochondria. So they can face the amount of free fatty acids that

currently are consumed. They will not be stored. They will actually start using your fat issue because

they don't have the glucose now. And there is a requirement for energy that is coming from the fat.

And this is why this re-education actually shifts the balance and people start to lose weight.

It's crazy. It's completely against what we are being taught. However, there is the carbohydrates

that you have to consume through vegetables. Of course, there are carbohydrates everywhere.

When you are doing ketogenic, you have to cut on everything. And that have their consequences

because you need the vitamins, you need the fibers. This is why paleo is more of a diet that I believe

because it's mostly about natural food, consuming good free fatty acids and vegetarian. So it's

mostly nuts and avocado and olive oils and butter, which is great and coconut oil, etc. Those are

good free fatty acids that supply me with great energy and very low carb diets.

And it is about metabolic flexibility. It's so interesting to hear you speak this way because

it really reinforces in me this idea that if you're heavily on a cart, if you're on the glucose,

if you're the head of the glucose-carrying parade, that process of re-educating yourself,

because your cells know. It's almost like the factory has been shut down for however long.

Right? And so now we need to restart the machinery and it can be ugly at the beginning.

But if we can get to that world where we can kind of flip back and forth, it allows us to get to

the best of all worlds. So going back very quickly to the, and we're not going to stay on endosymbiotic

any for much longer, but can we talk a little bit about this symbiotic influence? How it would

influence modern immune signaling? Because the immune system, we were talking about this offline

earlier on in another subject. Again, we don't think of it as a mitochondrial issue.

As foundational as mitochondria is to the cell, proper immune balance and function is

foundational to our ability to be healthy and age well and not have chronic disease.

So I don't know how many people know that, but the function of immune cells really depends a lot

of mitochondrial function and actually the different cell types that we have in our blood and in

our immune system also differ in their mitochondrial function. They differ in their mitochondrial

content, number, quality. So it's very different. So for example, if you want to stay the cell to stay

in a stem kind of senescent state or quiescent state, the mitochondria actually not active.

They only rely on glucose for metabolism. Once the cell needs to differentiate to different

cell types, then they start activating their mitochondria and now different types of cells will

carry a different amount of mitochondria and actually they are controlled, their differentiation

state, are controlled by the function and the number of mitochondria within those cells.

So it's really critical to have good and functional mitochondria in the stem cell that

will eventually produce all the immune cells that are acquired. When there is an immune

requirement in the body, there is a pathogen that is inflated or whatever, then the mitochondria

need to be very active and this function is being tested. An antigen produced in cell needs

tons of mitochondria, okay? This is a fundamental requirement for the production of antibodies

or the presentation of antigens only requires energy and a lot of energy. So the function of

mitochondria actually fundamental for the immune system function and very, very important. When we

talk about immune function, it's not only about protecting the body from invading pathogens,

it's virus or bacteria, it's actually protecting our tissues from damaged components.

For example, while we are aging, there is an increase in the presence of cellness and cells.

Those cells are like dormant cells within the tissues. The fact that they are there, not functioning,

just there and secreting their factors is a damage in response. What should have happened?

Is the immune system should have come to that organ and clear them away because the immune system

is not functioning? Well, you get them accumulating within the tissue and inducing further, further

damage. So the function of the immune system is not only against foreign pathogens, it's also

against damage, dead cellness and cells within our tissues. They have to be removed by the immune

system. So there is a very strong connection, for example, between immune dysfunction and Alzheimer's

disease, immune dysfunction and metabolic diseases, pancreatic diseases, kidney insufficiency,

there are many connections between these two organ systems, the immune and further organ

infection mediated by mitochondrial dysfunction. And you had mentioned earlier, before we started

recording, you had mentioned something about the immune cells started over producing,

it was over producing mitochondria or they start over replicating. I can't remember.

Yeah, yeah. So it's really dependent on the type of the cells that are produced because the

immune system is composed for many, many different cell types and eventually the type of cells that

will be produced is dependent on the mitochondrial content and function and special characterizations

of the mitochondrial within that cell type. When immune function is over active, when you see

the real function over active autoimmune disease or yeah, it might be due to impaired mitochondrial

function in a certain cell type within the immune system. Okay, it's important to look also on

the specific cell types, yes. The headline that people know, if anybody knows about mitochondria,

they know that they produce energy, right? That's that's going in position, but

you, I think you and many other scientists talked about the micellular sentinels.

They also sense the environment. They also make decisions. They also communicate as a warning

early warning signal in the cell, like, you know, like they, they'll sound the alarm. Basically,

like, can we talk a little bit about how they sense the environment? What are the other things

that they're sensing for? There is a close relationship between what happens in the nuclear

environment and the mitochondria. The sensing that we talk about is mostly environmental sensing,

for example, the nutrients or the oxygen that currently exists within the environment of the cell.

And then the mitochondria sends signals to the nucleus. There are many proteins that are on

the mitochondria in their day-to-day job. And then when there is a stress signal, they will

ship that protein into the nucleus signaling that now the nucleus needs to react. What does it

mean to react? The nucleus can now induce gene exploration of proteins that are required to

stand in stress conditions to allow the cell to be more active in certain directions versus

others to eliminate reactive oxygen species or to increase the number of mitochondria. That's

what needed. I've just said, for example, when you're controlling the nutrients and now there is

more quifati acid, you need more mitochondria. Let's restart mitochondria by your genesis.

If there is now a reduction in the needs of energy, let's start mitochondria and eliminate some of

the mitochondria. So all of that is a crosstalk between the mitochondria, the environment and the

nucleus. It all goes back eventually to gene expression and protein production, etc. So the

mitochondria behave like sensors. There is something very new recently in the past few years

that speaks about mitochondria also a sensor in organelles between cells. So now is it a phenomena

known as mitochondrial transfer. Cells can produce this tunnel in nanotubes like tunnels between cells

and they can transfer mitochondria to neighboring cells. Come on. I know this transfer is

actually induced by stress coming from the cell that is in demand. So one of the stress

signals is that I don't have enough mitochondria, I have a dysfunction in the mitochondria and now

the donor cells will create those nanotubes and transfer the mitochondria to the demand in cells.

We see that in cancer between immune cells transferring mitochondria into cancer cells,

the cancer is using this mechanism to actually extract mitochondria from the immune system in order

to walk in a more efficient way. This is maybe a mechanism of how in the future we will target

cancer and try to cure. That's why. Wow. Element we see transferring mitochondria in the brain

through macrophages from the immune system transferring mitochondria into microglia cells in the

brain and rescue in function. There are many systems where mitochondria's function,

mitochondria transfer have been shown and it is a pure signaling between cells and it's beautiful.

So that's incredible because that's almost like in a healthy cell or in a cell that's not

fully broken yet. It's an emergency that says, I don't have the energy to make my own new mitochondria.

Can somebody send me some over so I can survive this, right? And then if that doesn't work,

then I guess at that point that's when the cell would eventually become a senescent cell and

become a more damaging cell. But how do you shut that down for, how do you shut that pathway

down for cancer and not for the systems that need it? I guess is then. That's a million dollar question.

I had a question here and I think we can now establish that at least from your work and from

everything I'm hearing you say, we can say that when it comes to chronic disease,

it's less of a chicken than the egg thing. It's probably starts with mitochondrial dysfunction

versus mitochondrial versus the mitochondrial dysfunction as a downstream effect.

Although my guess is once you get into that spiral, it doesn't matter anymore but the way to fix it

is going to go through the mitochondria. Can you talk a little bit also about how mitochondria

communicate danger to the rest of the body? You talked a little bit about it at a cellular level.

Is there another mechanism that is more macro or does it all happen kind of through the nucleus,

the genetic expression? Is it basically that process? So there are actually also messaging of mitochondria

between cells that are usually delivering stress response or damage responses. Those are called

exosomes so cells usually secret content from the cells and they contain fragments of mitochondria

and those exosomes are secreted out of the cell and they are actually selling a signal to the immune

system for example or to the brain. So there are multiple elements of crosstalk between the internal

inside cell mitochondria to what happens in the environment and it's not fully resolved and this

is not my field of expertise but it is known that exosomes carry damaged mitochondria as a signaling

to the immune system to say this cell is currently damaged and needs to be cleared. Wow. Wow.

That's wild. I mean, guys, I hope you're geeking out on this. I'm fascinated. This is so

interesting. Okay, let's move into mitochondria and rare disease and then I think I want to

and then we'll talk about mitochondria and aging. So let's go micro and then we're going to go

macro. So a lot of your work started with rare disease, right? Rare mitochondrial diseases.

Do you want to describe a few of the conditions that you kind of are there a few conditions you

really focus on initially? Yes, yes, absolutely. So we started our our therapeutic approach is

actually to harvest stem cells from the blood and then enrich them with mitochondria. We are doing

this outside the body. So collecting from the blood outside the body and then enriching

with healthy and functional mitochondria. Those are blood stem cells. It means when they infuse

back to the blood they will engraft in the bone marrow and start producing healthy cells of the blood

and the immune system. So the first disease that we looked into was an ultra rare disease that

starts with a bone marrow failure. So the stem cells in the bone marrow of these patients are failing

though mitochondrial failing and that means that the lineages of blood cell formation are disrupted

and the disease that we started because we realized we first need to show that we can fix the

blood system. What happened later on, I will tell you, but the disease that we chose was a very

special disease that first of all is not inherited from the mother. It's a genetic disorder that is

not inherited from the mother and the patients are born with a huge deletion in the mitochondria genome.

Okay, we are suffering of course from lack of energy and many other functions of the mitochondria

which means the first symptom is that they are not growing like their age match.

So they're failure, full failure to thrive and they have a bone marrow failure and then we said if

we'll harvest the stem cells from the bone marrow and we will augment them with mitochondria coming

from their mother. It's actually an identical mitochondrial genetic source but without the deletion.

Okay, that was the concept initially and it's not about the business model because there are only

about a hundred patients in the world with this disease. It is called Pearson syndrome.

But it's about understanding like can you, you're almost inducing endosymbiosis. Exactly,

that's exactly what we are doing, replicating what happened back there. That Pearson is also

a multi-systemic disease. When you see these children, they are all dying during childhood but as

the disease progresses, it started moving from the bone marrow into other organ systems. So they

start having kidney insufficiency, they start having diabetes, they have muscle weakness, they have

neurodegeneration, they have cardiac issues and when you think about it they're just like an old man

in a young boy's body. So it's just, it's a replication of the aging process in a very clean

genetic background of a mitochondrial dysfunction. So we actually realized that this is the best disease

to study the impact of our therapy in a multi-organ failure just like happens in aging.

So without treating these children and what happened was that we improved more than just the

blood function, just the hemoglobin or red blood cells production. We started seeing that these

children start getting more energy and the children who were at six or seven years old in a baby

stroller or in a wheelchair started walking and getting more energy, being more awake, more hours

in the day, the kidney insufficiency stopped progressing and that was, it was mind blowing so we can

actually impact with the same therapy that only enriches the blood stem cells with mitochondria.

By the way, causing the immune function to be better and now we see an impact on distal

organ systems, on the brain, on the muscle, on the kidneys. So it was, you know, a disease where we

can really learn so much about the potential of the therapy moving forward. So currently we are

in phase two for these Pearson patients and because it is so rare, so probably only a few patients

to get us through the approval policies because there are just no more patients. But then obviously

when we started, everyone looked at us and said, you're going to transplant mitochondria in aging,

right? And then reverse aging, you're going to do anti-aging. And you said, okay, for real,

yeah, it's going to take a while, but the targeting of a very specific mechanism, which is

the mitochondria, not by trying to improve one function because mitochondria have thousands of

hundreds of functions, right? The complex. But by replacing the entire organelle, that was the

approach that we took. And then we said, we have to be able to measure this. And as I told you,

there are no blattest to measure mitochondrial function. So we developed them. And then we

directly, those biomarkers, we could validate the biomarkers in the patients with the mitochondrial

deletions and then tested whether before and after treatment, you see an improvement in mitochondrial

function. So that was very important for us. So when we started, it was just this Pearson,

with maternal derives mitochondria, and this is really non-scalable. When you think about us moving

into aging, we can't really help mitochondria from our mothers, right? They are no longer a

source. So we developed a bank of healthy, functional mitochondria that are actually coming from

donor placentas. So women who give birth, everything within me now, everything is very female-oriented.

So the mitochondria, only from the mothers, the donation of mitochondria comes from placenta,

from women who give birth. We are female founders and more than 75% female in the company.

Yeah, very, very female-oriented. But now we have a bank of healthy mitochondria that we can

use across the board for anyone that will require this treatment. But we didn't go into aging yet.

Because we see the impact we see in children is because they are young and they are generating

easily. Let's go into an age-related disease and demonstrate an impact also in elderly people.

When we looked for disease where the bone marrow is failing, the stem cells of the bone marrow,

and that was Nielo-displastic syndrome, MDS. And those are people that are 60 years old and older,

and have a severe anemia, they are blood transfusion dependent. And straightforward thing we'll do

to improve their stem cell function and to see an improvement in anemia. And that was indeed what

we started seeing. So this is currently in phase one and retreat patients, but those patients

have other symptoms of aging, of course. So for example, one of these patients had a kidney

insufficiency with blood creatinine that was high and he was already scheduled to start dialysis.

And then three months after treatment, you start seeing a decrease in the creatinine levels in

the blood, and currently he's on normal creatinine levels. So not only his blood

improved and he is no longer blood transfusion dependent, also his kidney function improved.

Let's face it, you can't change your biology, but you can support it intelligently. A lot of

products chase surface-level results while ignoring what actually drives resilience underneath

communication. When signaling gets distorted by age stress or environment, repair becomes

less coordinated. And this is important and especially in skincare. Vitali understands this.

They first earned by trust years ago with pharmaceutical grade copper peptides,

like GHKCU, one of the most research regenerative signaling molecules that we can get access to,

that actually naturally exists in your body. Now Vitali evolved that science by introducing

exosomes, the body's native messengers. They use zero age exosomes, which means the signals driving

repair are cleaner and more efficient. Paired with copper peptides, it's less about forcing change

and more about supporting skin to do what it already knows how to do. If you think about longevity

in terms of mitochondria, signaling, and long-term resilience, Vitali is skincare built for your

biology. All you have to do to get your hands on some is visit VitaliSkinCare.com and use code

knack20 for 20% off. It makes so much sense, right? You're going at the stem cells in the bone

marrow. The stem cells in the bone marrow are the found, I mean, if there is a fountain of youth

in the body, if there's a fountain of regeneration and repair, it's those stem cells and they will,

and I think you said this earlier, they will differentiate into many different cells that

are applicable to many different systems. So it's the elegance of this is getting it at such

a foundational level that then the body just decides what the next priority is on the list.

Exactly. That's what it is. That's wild. But I just want to go back to that childhood disease

just because it's my own curiosity. Would that disease not also be a really good candidate for

some kind of gene therapy someday to fix that deletion in the DNA? Many, many tried, of course,

so the complexity of that. So we know how to fix genes in the nucleus in the mitochondria. It is

way more complex because the DNA is right within the two membranes of the mitochondria to deliver

components for fixing the DNA to pass through these two membranes and then you not only have one or

two copies of the DNA, you have multiple copies of mitochondria. So to fix that is more of an issue.

And you're just keeping them alive until somebody figures that problem. Maybe, yes. And

they will need more mitochondria, we will supply them with. There's another accelerated aging

disease where it's not the same one. Progeria. Is there an application for progeria

with mitochondria or is it different specific gene that is mutated and causing the disease? And I

think a gene therapy in that case will probably be applicable. So within the context of this

discussion here, is there something to be said about mitochondrial resilience in all this?

I think we have a way to control our mitochondrial resilience. I wouldn't wait until we age and

develop chronic diseases. I think we can definitely behave while we are young and maintain

our mitochondrial function. I think getting that into our awareness actually starts resonating

very early in our lives and it will impact everything we do. It's the clarity in our brain and how

we think it's the slip quality. Our metabolism and our ability to absorb food and how do we

behave when there is an infection? When our body needs to activate our immune system,

so we cannot predict when there will be a wall pandemic or when our immune system will be challenged,

we need to be prepared to that. And being prepared to that meaning our mitochondria need to be

resilient to all these genes. And I think many of the surroundings, the air pollution and the

water that we drink and the food that we eat, the medications that we take, they have a very strong

effect on the mitochondria and not positive one. So where to that all the time and making sure that

we consume only things that benefit our mitochondria is something that we need to take in mind if we

want to age healthier. Yeah, I love that. I have a question. This is a little bit at a left field.

Do you have an opinion on non-native EMFs? On what? Sorry?

Non-native EMF, electromagnetic frequency. Like a lot of people talk about the impact of 5G

on the cell. And you know, basically this new input that our bodies have not had to evolve.

You know, the earth has electromagnetic frequency, like natural of course. But, you know,

do you, and you may not have thought about this. This hasn't, maybe this hasn't come across your

desk yet or you're not here. You're so busy. So okay, so we can talk about that the next podcast

because there will be another one. All right, let's talk about aging a little bit. So when, at one point

in life, in life, do you think we start to feel or experience that decline? Is there, I've always

heard at the age of 30 is when things start to, you know, like up until 30, our ability to regenerate

and repair is really good. And it, and you know, 30 is an arbitrary number. It could be 32, 31.

Like, is it that 30-year-old where we start to really kind of experience that decline and is

that backed up by mitochondrial science, do you think? Or is it later earlier? What are your thoughts?

So we're currently measuring those mitochondrial functions in different ages. And I'm sure that in

two years, I will have a precise answer for that. Okay, but actually people say that it's starting

20. We start to age in decline. Okay. It's very depressing. I know. I'm sorry. Oh my god.

Yeah, but, but I think it's very different and very personalized between people and definitely

different between males and females, as we know, we age very differently. So I think when we will do

our analysis using our mitochondrial biomarker to determine the health of mitochondria in different

ages, we will take into consideration also the different sexes and then try to build those mitochondrial

systems. Yeah. Health and disease. And then they'll have a better answer. Yeah, I've got you.

There's recently been some noise about these two inflection points, particularly in women,

where aging accelerates. And I think one of them was at 40, which makes sense because that's where

menopause, you know, give or take a couple years. That's when it starts to kick in. And then 60.

Yeah. Do you think, I mean, again, I'm asking for opinion, I think this is an area that you're

going to actively be studying. But how much do you think this mitochondrial kind of drop in

function might be playing exactly into those and why? I mean, you know, is the loss of hormones

affecting mitochondrial health? Absolutely. 100%. And actually the decline, the mitochondria could

be the clock that caused the decline in hormone production. And that's where you see, so it's

what starts, right? And I believe in the mitochondria, that's all kind of the trigger for that,

because I told you about the involvement of mitochondria in steroid hormone production.

Let's try all the potential alone. Yeah. I will never forget that.

It succeeds already a multi-fructorial event. It's already when the mitochondrial dysfunction

starts circling back on different pathways. You will see telomer, shortening, you will see reactive

oxygen species, you will see so many dysfunction of the immune system, exhaustion of the stem cells.

All of that is happening already at 60. So it's already too late. This is why I mean that you

need to intervene very early to prevent dysfunction of mitochondria, which is one of the earliest

things that you see in the right forces. So I was going to ask about stem cell exhaustion.

Talk to me about stem cell exhaustion. Is it a thing? What is it? And do you think it's coming from

the mitochondria? I mean, I'm listening to you now. I'm like, everything's coming from the mitochondria.

Of course. Talk to me about stem cell exhaustion, because it's a term that I think gets thrown

around a lot. And I don't know that people fully understand what it really is and what it isn't,

and then let's tie it back to our mitochondria. Yeah. It's eventually you measure the outcome.

So for example, we know that the ratio between lymphocytes and other cell types within our blood

system is changing with age. Why is that? You see just the outcome eventually. You see a very

poor responding immune system, but it starts with your stem cells. This is how we know that.

So exhaustion of stem cells means cells are actually lacking the energy to start differentiating.

Okay. Yeah. Because that's what you need as a trigger to start producing new blood cells.

New blood cells meaning new immune cells and different subtypes of immune cells. So as I look at

stem cell exhaustion is their ability to renew themselves. A stem cell has to be able to renew itself

and all come to stop what's in new daughter cells that are differentiating. So the

function affects two pieces. Their renewability and the differentiation capability.

And the lack of energy is something that just puts cells into senescence. Just like you said,

if I don't have energy, now what I will do is just hibernate, right? I don't waste energy.

I'm sleeping now. Don't bother me. And not bothering, meaning I'm not doing my job.

I'm not replicating. I'm not differentiating. I'm not producing the cells as I should produce.

Stem cells also, of course, have a role in regenerative capacity. So when they migrate into a tissue,

they will need to renew that tissue. Every renewal process requires energy. The production

of proteins within a cell that is one of the most important piece of the cell needs to do,

either secreting factors or producing enzymes for the cell to function, it all requires energy

and mitochondrial function. I think this is what exhaustion is all about. Renewability,

differentiation, and regeneration. Yeah, no, it's foundation. It's foundational.

Like the immunosenscence has got to be, fundamentally, you've described it three times now.

It's a lack of energy. Just to go back to the zombie slash senescent cell,

I've heard them described as grumpy old men. They don't even just sit there and hibernate.

They secrete cytokines and inflammatory markers. And so in the absence of a neighbor that will

create one of those nanopores and donate mitochondria so that they can live to fight another day,

then they are like, okay, fine then, I'm just going to take everybody down with me.

Exactly. Kind of attitude, which is interesting. Okay, you've referred to neurodegenerative

disease as a couple of times. How foundational do you think mitochondria role? Is it a foundational

role? Okay, because we talk about accumulation of plaque. We talk about the death of neurons,

which I'm sure you're going to sit there and explain to us in a very clear time.

Is everything to do with not enough mitochondria? But, you know, in treating these diseases,

should my mitochondrial treatment fundamentally be one of the pillars, because it's, as you said,

a few times, when a lot of these chronic diseases, it's not just one thing, right? It's never going

to be just one thing. But should addressing mitochondrial function foundationally be one of the pillars

of dealing with these things, whether it's slowing them down, reversing them or avoiding them

in the first place? Yeah, what you need to do with brain cells is really prevent their death.

Death. What happens in neurodegeneration is either the cells stop functioning and they remain stuck

in the tissue. Like we said, all they are dying and again, remains stuck in the tissue and they

are inducing further damage. When we talk about inducing mitochondrial function is actually

preventing the death of neurons and prolonging their life and activity within the tissue, because

neurons are not regenerating, okay? We avoid the amounts that will keep us alive all our life.

And the amount of energy that the brain demands is huge, it's enormous. So, where does it get

this energy mostly from the mitochondria? It's more than 80 percent coming from mitochondrial function.

So, of course, neurodegeneration, especially in aged individuals, is due to mitochondrial

dysfunction. We see that greatly. As we age more, more components join the party and of course,

it's accelerating everything. But the earliest signs is really mitochondrial dysfunction.

The problem is, how do you solve mitochondria dysfunction in the brain? That's really problematic.

You have to only handle what's in there. You cannot deliver anything new. It's very, very difficult.

Now, even drugs are difficult to brought into the brain. So, it's a huge challenge. When we

have treated our patients, they also suffer from neurodegeneration. I mentioned Pearson syndrome.

There are also other more neurological diseases like care and siren syndrome and least syndrome,

all our primary genetic mitochondrial diseases. And we observed an improvement in neurocognitive

function. We don't really know how to explain it. I have to tell you. Because if you remember,

we treat the stem cells in the blood, how does it influence the brain? But we have seen it because

it's like, again, the immune system and the signaling. What you're doing is getting in at such a

foundational level that allows the body to do what it does. So you don't have to get to the brain.

The body is like, we can get there. All you got to do is give us what we need. It's so incredible,

right? I'm going to use the word elegant again because it is such a, and I mean, nothing about

this is simple. But it is truly so simple that if you can get to that first piece where the

body is producing it's what it needs, then it can do what it needs to do. Like that is just wild

to me. But we are scientists. I mean, and we have this curiosity to understand how

course they're walking. And of course, drug development. If you want to succeed, you need to

understand how walking. This is what initially we only focused on the bone marrow and the blood

system to show improvement. But eventually the impact that we see in the patients, that's our

trigger to go way far and beyond, just as rare diseases. And the genetic disorders really try,

we feel very brave now. First of all, our therapy is safe. So it's not, do know how, first of all,

in the multi-organ improvement, we had a patient with severe epilepsy and stroke-like episodes

on a monthly basis. But for six years, we prevented those after a single treatment, which was like

unbelievable. So we really try to understand how to deliver this therapy way broader. The brain

is a very interesting but very challenging organ. We will just have to face the clinical outcomes,

to see them. And eventually that would be the proof. I don't think we'll ever understand everything

about how it's exactly walking. But I think that's the most important thing because if you save

the life of a child with a person's syndrome, but you didn't fix his brain. I mean, that's

so it's yeah, you didn't you didn't achieve the ultimate goal. So we can say that metabolic disease,

like diabetes, non-alcoholic fatty liver disease, cardiovascular diseases,

are gonna have that very minimum have a mitochondrial component. If not, you can

additionally link to mitochondrial under-mits malfunction or under-performance.

Are there do you think are we misclassifying diseases that are actually mitochondrial and

origin? I mean, fundamentally the question is, do you think there's a disease that isn't founded

in mitochondrial dysfunction? You can try and search in any search engine, any disease with

mitochondria, you will find a connection. I tried this before, you can go ahead and do that,

but definitely, I mean, whether it's started a disease or it's an outcome, this is a question

whether it can tell you for certain any disease will benefit from improvement of mitochondrial

function. Okay, that's because fundamentally if you get more energy, you can fix anything.

We're being the same. Talk about, you spoke about diabetes, insulin production is an energy

energy process. It has to be coming with improved mitochondrial function and then you'll get more

insulin production, controlling of insulin production, controlling of glucose metabolism,

all of that is energy dependent and mitochondrial dysfunction will actually induce further

damage into the cells. If you improve that, you have a better chance of to fix the even the initial

problem that the cell has, cell accumulates mutations, for example, and now you improve mitochondrial

function. You have better chances to initiate and DNA damage response, all to improve the

function of those machineries that will fix the cell and if it's not mitochondria will induce

the apoptosis, the cell suicide to eliminate the bad cells, which is also fundamental. So

yeah, I think there is even, I tried it, even one disease that doesn't have mitochondria

eventually and those diseases will probably benefit for mitochondrial function, yes.

Yeah, I would think so, even like anything in the eyes, like as we see the decline in the

eyes, like the eyes are so dense in mitochondria. For example, our call, I had a full discussion

about the different diseases that could benefit for mitochondrial transplantations. You name it.

All right, let's move into mitochondrial biomarkers, you know, measuring the invisible. So

this is what your work really becomes also about, like there's obviously the mitochondrial

transplantation, but as you said, in order to quantify what you're doing and to understand

the needs and the outcomes, it's really about measuring something that nobody really has been

able to directly measure so far. And that's a big aspect of your work. So, so clearly, I mean,

you know, we don't measure them because we can't. We don't know how or we haven't developed

those strategies. So what are the most promising biomarkers in mitochondrial biomarkers you're

seeing coming out today? First of all, you cannot treat, but you cannot measure. Okay, this is

fundamental knowing that drove us to develop those biomarkers. We wanted to develop a therapy,

but realize there is no way to measure our success in this therapy development. So let's develop

biomarkers. But then when we were exposed more and more into this world of mitochondrial diseases,

we realized that it is way beyond just the primary genetic. And there is a whole world of

secondary mitochondrial diseases and a whole world of age-related mitochondrial diseases.

And you see people that look completely perfect. I mean, they go to the doctor, they say,

I feel very frail, I feel very tired. I don't have the power at the end of the day to climb my

stairs to go home. And they say, your blood tests are perfect. Nothing shows that you have any

disease. Exactly. So we are not measuring, obviously, what drives our mitochondrial dysfunction.

So the most important thing, mitochondrial dysfunction is it's it's it's streaky, right? Because I

just told you they have so many infections. So which ones are the ones we should pay attention to?

So then no of mitochondria are critical. Even if you have some of the mitochondria dysfunctional,

but you can increase the content, you can eventually increase the content of the good mitochondria,

get enough mitochondria to get enough energy, okay? So the number of mitochondria are really

critical. The function that we are looking at is of course the ATP production, but ATP could come

from glycolysis too, right? Not less mitochondria. So we are coupling the ATP production to the

respiratory chain activity of the mitochondria. We are doing home. Because eventually you know,

you need to know what is the specific ATP produced by the mitochondria per single mitochondria

within the cells. So we're doing all three of them together. And those are the three biomarkers

that we're using to calculate the mitochondrial scrolling of a healthy individual versus a child

or an adult with the mitochondrial primary mitochondrial disease. And now every person that will come

and be tested with this biomarkers, we can say, your skull is somewhere here. Your healthy,

age-match control is here. So you're doing great. All your age-match control is here. You're here,

primary genetic mitochondrial disease is out here. You can go further down or you can get a therapy

and move up the scale into your age-match control. You can also go on a hill into a younger phenotype,

which would be fantastic. But that allows us to really measure the quality content and function

of the mitochondria in different people. We are also looking, of course, at the mitochondrial DNA

because we want to know the mutation load in the mitochondria, which is fundamental to all this

non-functioning mitochondria. And there is also another biomarker that is released from this

organ that is called GDF-15. GDF-15 and mitochondrial dysfunction goes hand-in-hand.

So, overall five biomarkers that are currently used in our clinical studies to first call different

people different ages with their mitochondrial scoyne and then test how our therapy improve the

function or the levels of those biomarkers in the blood of these patients.

It's like a biological age test for your mitochondria. Exactly. It's a biological aging test for

your mitochondria. Exactly. Which is going to drive your biological age. Exactly.

Wow. This project, I have to say, was funded by the foundation called Countdown for a Q. I've

just returned from Atlanta for an annual event of the Countdown for a Q, where the people who

drive this foundation are people who look completely normal. When you speak to them, they're telling

you all the symptoms that they are suffering as to a secondary mitochondrial disease, young,

beautiful, healthy people. They look very healthy. Eventually, when you test them, all the

bloods are fine. There is nothing, but they cannot climb the stairs in their house. They can come

to a situation where they can't even feed themselves and they need help. So, it's unbelievable.

It's mind-blowing how needed those biomarkers are. And this foundation has identified our project

as one of the both funding and they gave us the grant to develop those biomarkers way far

and beyond than what we initially intended to do. And I think I told you, in two years,

we will meet and I will tell you exactly what should be the scope of the mitochondria at each

one of the ages. And then we can start screaming for people. Wow. Wow. Okay. So, we talked a bit

about the transplantation that were yours essentially in a very simplistic way, trying to induce

endosymbiosis outside. You're using donor mitochondria from cord blood. So, you know,

from placenta, sorry. So, essentially, you know, unless we get into a world where we all

bank our moms mitochondria when we're born so that we can use, you know what I mean? Like,

later on in life, I can see you on a prenatal level, at some level, that mitochondrial

support for the mother would be wildly important. I mean, it's wildly important

through your entire life. Is there anything in the transplantation trials originally that surprised

you? I think the brain, the impacts on the brain was something really surprising to us.

And the kidneys as well. I mean, the improvement, because usually they say that once kidneys

phase, you cannot reverse kidney insufficiency because of the fibrosis that happened. So, I think

that was really, really surprising. And but overall, knowing how important mitochondria

I wasn't that surprised, if I really didn't know. It was amazing mitochondria. And I also knew that

the placenta was very unique in their nature because they just fed a baby for nine months and now

we are using it, we are behaving like it's trash. And all of a sudden taking that very, very healthy

young organ, producing the mitochondria. It was mind blowing. It is way more active than blood

mitochondria, for example. So, if you compare mitochondria from placenta to blood mitochondria,

you will see there are 10 times more active than the blood mitochondria. And they contain more

mitochondrial DNA than blood mitochondria. So, overall, it's like a super organ for mitochondria.

And that I knew for my PhD already. That's, for example, mitochondria is very unique. And we found

something to do with this trash. So, I'm very happy about it. Are there any safety concerns

that have to be solved, do you think? Like, could it, I mean, I guess in this case of an existing

cancer, you've already said that the cancer is already hijacking sometimes. Healthy cells might

mitochondrial stores. Are there any other safety concerns that have come up for you that you've

seen so far or that you think, well, you know, we might really need to... Definitely. I mean,

there are always safety concerns around the new therapy and intervention with some evolutionary

conserved processes that was always frightening. This is why we started, by the way, first of the

maternal mitochondria into the children because we didn't want to go first into an allogeneic donor.

But today, the main safety concern, well, can we really mix different mitochondria in individuals?

Can I take or borrow mitochondria from one donor and use that? Will I have any immune responses?

Will we get rejection? And eventually, we didn't see any immune response, again, the mitochondria.

There are no anti-mytocondyl antibodies that are produced due to this process. So overall,

in 27 patients so far, it seems to be safe and tolerated. So those risky aspects where

have been overruled, the cancer, I think, is always an issue. I mean, will we induce

cancer because of this mitochondrial orientation? But actually, you know, we've done... We went to

one of the world's experts. We focused, if you recall, we are focused on one

old age-related disease called Mielo Displastic Syndrome. And MDS had the risk to develop into

Leukemia to AML. So when to one of the world's experts, before we started those in patients with

MDS, and he has a mouse model, this is a lab in Memorial Stronkettering in New York, lead by Dr.

Omar Abdul-Wahab. So he has a mouse model that is accelerated age has MDS and develops AML

and all the mice die from AML. So when we took the stem cells of that mouse and we transplanted

them in a healthy mouse, all of the mice died within four weeks. If we augmented those stem cells

with mitochondria, and that was supposed to be only for safety, the question was whether we

induced faster the Leukemia. Did they die in a week? The answer was they actually have an extended

lifespan and it did make sense to Leukemic progression. So that was comforting. I said, okay, we are

safe to go into humans now because not only we are not accelerating Leukemic conversion, we are

actually protecting them and we are delaying the Leukemia. Well, based on the conversation we had,

you're re-engaging the immune system to do what it does. It sounds to me, again, oversimplification,

fuzzy overview, but based on this entire conversation that makes complete sense. Okay, we're

down to a last couple of questions. Stay with me. I could keep you here all day. I would imagine

that down the road when this has been refined and tested and this is going to become at least

as calm in a stem cell therapy, but I would imagine that this would augment stem cell therapy.

Like, you know, we're seeing so many amazing things coming out of stem cells, exosomes,

but now if we're bringing the work crew, the stem cells with the exosomes, the instructions,

but now we're also providing extra energy to the cell to actually do the work.

You can imagine that this would explode in terms of efficacy, or am I missing something?

I love it. Yes, exactly. We all think about how to combine therapeutic approaches in order to

reach the maximum abilities of a human body, and this is exactly it. So if you harvest now stem cells

from an elderly individual and you infuse them back, they actually all, the mitochondria are all

it won't be enough. Taking those stem cells and now augmenting them with the young and healthy

mitochondria will boost their activity. That's exactly what happens also when you grow cells in

culture in order to produce exosomes. Growing cells endlessly in culture caused the cells to

age. There might be a kind of aging. Now if you want to produce healthy functional exosomes,

boost the cells with mitochondria to get more exosomes and healthier exosomes. So for the,

it's everything, you know, people are trying to reprogram cells to come back to their young

nature, like IPSEs, blue potent stem cells to go back and be embryonic like, right? Those are

the newest things with gene therapy, trying to overexpress the amannacophactors to make cells

young and healthy again. But how do you fix their mitochondria? You cannot do that.

They are amannacophactors. So let's augment them with mitochondria. And then you see how this

combination therapies will solve multiple problems at the same time, and it's not one plus one.

It's exponential because of the impact of mitochondria. Do you have any thoughts on NAD,

NAD precursors, supplements in terms of their importance? Something that people can do

to support mitochondrial function at a foundational level? And is there any other

support that stands out to you? Yeah. So NAD, of course, is one of the important substereits,

the cells mitochondrial function, super important. Yes. And actually available and consumable by

the cells, so it's something that's relatively well-studied, and it seems like to produce a good

results. In addition to NAD, you can see coins in Q10, very important. You know, and not

you, we know. So a structure that can be consumed by the cells and be actually available for the

mitochondria. Coins in Q10 is one of the most important co-factors for mitochondrial energy

production. And important to know, it is blocked when we are taking statins. So anyone who's taking

statins to reduce the cholesterol is actually blocking the synthesis of coins in Q10 within our

cells. And this is why supplementing with coins in that case is a good thing. And one of the

things that I've spoke about, you know, raising your free fatty acids that induces your mitochondria

activity and mitochondria genesis. This is important. Easily controlled by the food that we eat.

Cing, consume oxygen, do yoga, because it's so good. Yes. For mitochondrial activity, and one

thing I tried on cells on culture and is working, a component called resvertile. It is found in

grapes, red grapes only, and actually walks. So again, the source is important. The no one is

actually, but the resvert one is something that induces mitochondrial biogenesis. So the increase

of mitochondrial content within the cells, I know I tried. It's working. Are there any lifestyle

or other interventions that actually you believe really do move the needle on mitochondrial

biogenesis? I think free fatty acids is going to be one of them just because of the energy.

Is there anything else? Like, so I'm going to throw a couple of things at you and you can give

you can give an opinion if you have it. There's red and near and for red light, infrared

sonas, hyperbaric therapy, fasting, hyperbolic therapy, hyperbolic chambers. Yes, induce mitochondrial

function, by the way, increase also stem cell content within the blood. Great signs behind it,

totally agree. I don't know about red light therapy. I'm not sure if it's anything. I'm all

about the signs of eventually. And the last one, what did you mention? Our infrared sona

or fasting, fasting. And I would also be the closest, right? So absolutely.

Just as mitochondrial function, yes. Again, exercise. Absolutely. Okay, when you build muscle,

what you're actually doing is increasing the mass of mitochondria within your fibers,

muscle fibers, that's all what it is. This is how you look at what you need 14 in order to

expand mitochondria within the muscle fibers. And what you see is more energy, the more

mitochondria in the muscle, more energy, and then more tolerance and exercise tolerance.

Excellent. Also, when you exercise, of course, you consume more oxygen, you feel better,

energized. It's all over. It's everything. It's great. Okay, last two.

What is one mitochondrial myth you wish would just disappear?

Oh, that's a good. Well, you know, people think that mitochondria are single. Actually,

mitochondria are plural. So it's a mitochondria for one mitochondria or plenty. And with people,

every time they're surprised, oh, we don't only have one mitochondria within ourselves.

No, we have tons of them. So this audience, you know,

it's okay. Last one. And this is something you mentioned at the beginning of the podcast

that I think is so important. You talked about emotion. You talked about joy. You talked about

impact of our of something that is really not tangible, but that impact on mitochondria. Do you

want to speak to that a little bit? Because I think that it's, I want the audience to walk away

with something that they can start tomorrow, right? And just from a scientist who's been so deep

in this for so long, I'd love for you just to share with the audience your thoughts on our

emotional, spiritual inputs that can they affect our mitochondria? Yeah. I think when we

all, when we feel good, I mean, we feel energized. We feel so powerful. And I think when I go to

visit my parents and my father is now 84 years old, and unfortunately, suffer is from a third-age

epilepsy and consumes drugs. The terrible harms is my wonder further. When I come to him, what I

tell him, that is sing, sing. When you sing it, it's like you float your body with all your energy,

and you feel so good. And now my mind thinks why is that? And how come one of the most surprising

things I've ever met in a scientific conference was a group coming from from Canada, from Toronto.

Therefore, a psychiatric hospital and they presented data that I was just shocked and overwhelmed,

schizophrenia, mania, depression, all these bad diseases of the soul are eventually bound to

mitochondrial dysfunction. I was shocked. I never knew that even. So our mental health really

depends on the quality and health of all mitochondria. That was shocking to me, and eventually

exactly everything is eventually bound together. Why should we live those long life, unless

we feel good, we feel healthy, we feel energized, and we're good health, mental health as well.

So they presented data showing the 30% of bipolar disease patients carrying mutations in the

mitochondrial genome. It's crazy. I think there's so much to it of how we we we capture our life,

our health, and how much of it is in our control in mitochondria. This is the case, we can really

control it by simple. Yeah, and that was I think that's what I was getting at. Like in a person who

is not chronically ill or has a serious condition, is it possible that bringing bringing attention to

living and joy and gratitude and in a positive mind can also have a very powerful impact on

how we age and how our mitochondria behave or thrive. Is there anything people can do when

they're in a position that they are ill, and they have to take medications that are

in a negative to the mitochondria, but saving the system. So you know what I mean? Like sometimes

we're in a situation where we need a medication to get us through a crisis.

Have you seen or are there things that people can do when they're taking medications that are

fundamentally toxic to the mitochondria? Like a statin, for example, you mentioned CoQ10.

Are there any other interventions you can you can share with the audience that they might want to

consider and talk to their physicians about that could be helpful to supporting the mitochondria,

which ultimately could support their recovery in some small.

So you know for mitochondrial disease patients, there is a list of drugs that are forbidden

for mitochondrial disease patients because they are harmful for the mitochondria. They can

further deteriorate. Of course, in some conditions, it is not possible, but there are drugs that are

more toxic to mitochondria than others. For example, I mentioned epilepsy that my father suffers when

he started on Valproic Acid, which is the first line of drugs that epilepsy gives.

He started deteriorating like crazy. And then when I was reading about it, it is known that

those drugs have mitochondrial toxicity. So if there are certain physiological conditions,

there are multiple approved drugs, I would look into the literature and see which one of them

has less mitochondrial toxicity. Of course, we can supplement just like you know, people who are

taking antibiotics are also taking probiotics in order to prevent the death of our gut microbiome.

We can supplement our mitochondria as mentioned with the supplement that you just we discussed

a minute ago in order to improve the mitochondrial function and to rescue that. So there are certain

antibiotics that are also harmful to the mitochondria. I would try to avoid those. Again, it is

available. It's a data that is available throughout the networks. You can easily know which antibiotics

have more mitochondrial toxicity versus others. So just being in attention into mitochondrial health

will eventually allow us to ask the right questions. Either our physician or sometimes it's

just the information that is available throughout the network. Then you can really find out so much

more about your health. My goal is that any drug that is being developed in the first stage of

development, the drug will be tested for mitochondrial toxicity. I was shocked to know that most of the

drugs, not most, but about 50% of the drugs that we use today have known mitochondrial

toxicities. This is crazy. You can prevent that. You can screen in advance for drugs that are safe

for the mitochondrial will prevent the outcomes of using those therapies. So this is

my message to you. It's so self-defeating. You're keeping in person alive and denying their

body the ability to do any kind of repair work. It's wild. All right, listen, we need our, you know,

this is like when you're the longest goodbye. I have to let you go so that you can go answer all

of these incredible questions and bring your incredible work to market, which I think is going to

be so unbelievable for everybody. So Natalie, please share with us any information that, you know,

anything that where people can learn more, where they can follow your work. If there's anything

anybody can do to help, I think just, please share with us anything that people or just even

follow the work. Yeah, of course. So we have our website, of course, MinoviaTX.com. We have our

LinkedIn and Instagram and we are also on Twitter. So I think, you know, just follow our activity.

We are trying to be as helpful as possible for the entire community and to implement the

importance of mitochondrial health. As you've just heard, it's not just about getting a therapy

or a drug approved. It's been mindful to our mitochondria very early on in our life as soon as

possible. And just bring it forward because eventually what we learn and experience on our bodies

could be beneficial to others. So share that information, follow what we do and give us feedback

and send questions. There is an info at MinoviaTX.com. Feel free to write to us and ask

and questions. We find the time to answer everyone. So do that. That's amazing. Thank you so much.

This has been, I can really, you know, I'm always, I'm always interested in my topics, but this one

got me. So we will remain Natalie, maybe in a year or two when you've had your next couple of

breakthroughs. And I think people will be waiting for that episode. I know I am. Thank you so

much. Thank you. It was a pleasure. If folks, just a quick reminder that all of the information

presented in this podcast is for information purposes only, no medical advice, no diagnosing,

no treatments suggested here. Before you try anything that you hear about or learn about here,

make sure that you check with your medical provider.