Welcome back to the event.

Our guest today will be speaking about mitochondria.

You're going to learn all about them and how they're the root of most of the chronic diseases we face, and even longevity, when you stay to the end.

Our presenter for this discussion is Dr Hemal Patel.

He's a professor in the Department of Anesthesiology from the UC San Diego School of Medicine.

Professor in the Department of Anesthesiology from the UC San Diego School of Medicine, professor Patel's expertise is in mitochondrial biology.

He's applied this expertise to the study of basic inquiry into cardiovascular disease, neurodegeneration, aging, diabetes and cancer.

Let's go ahead and jump on in.

Hey, hemo, welcome Glad you could make it Glad to be here.

Well, I'm so excited about learning about mitochondria, which are turning out to be more amazing the more I learn about them.

So what?

We will maybe just start off at basics.

What are mitochondria and why are they so important?

Yeah, so I think if you ask people into the survey, I think most people will get it half right.

Right, they say they're the powerhouse of the cell.

So they're the organisms that we incorporated into our biology billions of years ago, that allowed for this expansion of diversity, growth in terms of size and other things, so they provide the energy for everything that happens in our bodies.

We, as humans, have trillions of cells and there's trillions of mitochondria living in those cells that give us access to ATP, which is the energy currency.

The only cell type that really has no mitochondria in your body are your red blood cells, but every other cell has mitochondria, and so they become the conduit for creating this balance that you need to sustain who and what you are and then to thrive in those environments, and it's really this ability to generate energy that does this the thing that people don't really understand about mitochondria.

They're also the gatekeepers for cell death and survival.

So they've been incorporated into our cells and because they create this unique balance of energy, they also become the corner points for which a cell uses to make decisions of fate right Whether it needs to go down this one pathway for killing itself, to survive for the organism or potentially to survive under certain situations, and so they create that potential.

There's growing evidence to suggest that mitochondria may be involved in differentiation of different cell types.

So if you look at your neuron versus your heart, the behavior of the mitochondria is very different in terms of the energy they create, the signaling they create, and so there is sort of newer thought to think that mitochondrial metabolism and energetics may be a driver for differentiation as well.

And so now this unlocks the key to stem cells and all these other things as well.

So they're powerhouses in many respects in the body.

Well, the point you made about cell death and we've talked with other speakers about senescence and autophagy.

So what you're saying is that there's evidence that the mitochondria may play a key role in that whole thing, in deciding whether cells die or they become senescent, and are involved in that decision process there.

Yeah, so I mean, the other arm of autophagy is mitophagy, right, so mitochondria eating themselves, and so there's lots of quality control issues that come in, and so as your mitochondria become dysfunctional, we have to process them in our system to get rid of these dysfunctional mitochondria.

A lot of processes that people are interested in diseases, aging, longevity, all these things have pathways that lead to deficiencies in mytophagic processes along with autophagic processes, right, and so ways to sort of intervene in all these things.

People are looking at triggers that induce mitophagy and autophagy and all these kinds of pathways to do it as well.

But yeah, they're really gatekeepers in sort of keeping cell systems clean and sort of behaving in a normal homeostatic fashion.

So, like some of the supplements or even drugs that we've talked about that are related to autophagy and senescence, have interesting properties as possible longevity drugs as well, things like fisetin, cursitin and and as supplements or desatinib as a prescription drug.

Do these act directly on the mitochondria or is it through some other mechanism?

I'm sure there's some conduit where they all funnel into that energetic profile.

Um, you know they're.

I'm a mitochondrial biologist and I'm also a membrane biologist and it's interesting how those two systems connect together.

The membrane really is our sensor for the outside world and the mitochondria is this internal sensor that then internalizes that outward signal into a behavior phenotype.

And so all of these supplements and compounds likely impact the membrane in a unique way and ultimately the downstream effect of that is rebalancing and changing that energy profile at the mitochondrial level.

So whether they permeate through the membrane and have a direct effect on the mitochondria, or whether they just balance or change the membrane behavior to then ultimately change energy profiles, it at the end point always comes down to that balance of energy.

And one of the critical elements of that is we can't store the energy anywhere, right?

So once you make it, you have to use it, and so ATP gets churned quite frequently in our systems.

The heart generates kilograms of ATP in a day, yet you're not increasing your mass by kilograms because as soon as it's made, you're constantly using it, right.

And so it's this balance of keeping the system fine-tuned.

They can meet the demand that the body produces and needs for that energy and the mitochondria meet that demand over time.

Yeah, it's so fascinating.

When I went to medical school, we were taught that the mitochondria, as you say, were the sort of the batteries or the powerhouse, and that was their job the batteries not very interesting or sexy, and the nucleus, on the other hand, was the brain of the cell.

It had all the DNA and everything but what you're saying.

And I think there's growing evidence that the mitochondria actually have a lot of driver roles of fundamental level, and the cell membrane along with it are the brain, whereas the nucleus is more like the library it's just storing blueprints.

Yeah, I mean, the way I've been sort of thinking about it recently is the nucleus just sits there, right, it's just that there's no potential.

There's potential there, but it just sits there, whereas the mitochondria, the movers and shakers of the cell, they're moving around, they're dynamically shifting, they're sensing, they're, they're creating this information for you to, to respond, and and there's some evidence to suggest that they may be talking to the nucleus as well right that this energy balance creates this thing that's just sitting there and gives it potential to do more and beyond what it can do.

Yeah, yeah.

And those interesting experiments with malignant cells doing nuclear exchange, where they take the nucleus out of the malignants basically normal cells and malignant cells and they swap the nucleus in the cytoplasm.

And what was interesting and sort of counterintuitive is that the malignant property seemed to follow the cytoplasm rather than the nucleus.

But of course the cytoplasm is where the mitochondria are and the membrane, of course, is right around it, so it's fascinating.

Well, so what is it about mitochondria that make them underlie all the chronic diseases, or a majority of the chronic diseases that we're facing?

Like you know, we hear about them with Alzheimer's disease, with cancer, with cardiovascular disease, the diseases that determine our longevity, not to mention, you know, diabetes and obesity, and hypertension, and the other ones as well.

What's the common theme about mitochondria that allows them to have such a wide ranging effect on what seem like very different types of diseases?

Yeah, and I think it's because they're everywhere, right?

I think I don't know how anyone counted this, but if you do a Google search, I think it's like 30 something trillion mitochondria in your body.

They are an old organism that was incorporated in the symbiotic relationship with who and what we are.

There's a huge other side of science that's been focused on the gut, microbiome, and there's a gut to everything axis.

The gut regulates, and there's a gut to everything axis.

The gut regulates your heart behavior.

The gut regulates whether you have psychiatric disorders or not.

Your gut regulates whether you have cardiovascular dysfunction.

Back in the day we were doing studies with probiotics and how it would protect from ischemic events, because the gut would secrete stuff that would be protective to that biology, and so the way I've been thinking about this as a sensor model kind of thing, is that the gut's communicating with some entity in our cells and it would seem like that entity is probably mitochondria, right, the gut creates a lot of metabolites that then feed back into the rest of the system to then change the behavior of this energy balance.

To me, diseases are a manifestation of an inability or a supply-demand issue with energy.

Every disease gets consumed in a certain way because you don't have that balance in that particular state.

If you can rebalance your mitochondria, it's usually through this dysfunction, because you're not making the energy you need or you're over consuming the energy that you're making.

That creates all of these chronic diseases Pain, cardiovascular dysfunction, diabetes, aging all of these things are a manifestation of this misbalance of energy demand and supply, and mitochondria become the gatekeepers of that.

This goes back to the whole med school and the other aspect, the powerhouse thing, is an important component of mitochondria.

I think what we're learning to see more and more now is that they have a dynamic component as well in the cell.

The way they move, the way they shape, the way they behave becomes a resiliency factor as well.

So one of the things we're starting to see is that mitochondria are exists as living communities within your cells, and so every mitochondria is somehow connected to other mitochondria, so they're sensing and basically creating a profile across cell types.

It's when they get disrupted and lots of diseases will do this is the mitochondria become isolated, so they either start fizzing.

So one of the early thoughts in cancer biology was this concept of well, what triggers the cell to divide when the mitochondria start to fizz, become smaller and they're dividing.

That's typically a trigger for the cell to be like oh I got to divide, and so a lot of cancer therapies are targeting this fusion fission reaction within mitochondria.

If you can stop them from fizzing and contain this fusion aspect, you may be able to tell the cell that there's a signal to stop dividing and not sort of grow out of control.

So there may be some elements of this in terms of their dynamic shifting and what they sense, and so I really think that resiliency and longevity and sort of the things that manage chronic diseases are where you keep this communication completely intact.

Then you've got sync for calcium, you've got ways to signal, you've got ways to communicate and you have ways to maintain an energy balance.

It's when you see these mitochondria come apart from themselves that you see this traumatic disease.

A key example of this is the cardiac myocyte.

If you've never looked at a myocyte under a microscope, you should go find a microscope and get some myocytes and look at it.

It's the most amazing looking cell.

It looks like a box car.

It's got all these patterns and things and when you look at it under the electron microscope, it has these mitochondria that look like pearls that are just beaded together across the entire cell.

30% of the volume of a heart cell is mitochondria.

Your heart is constantly beading and it needs that energy to do it.

Every disease that we've looked at and my lab is a cardiovascular focused laboratory heart failure, ischemic heart disease, diabetic cardiomyopathy, stress-induced kinds of things that happen in the heart.

The mitochondria lose their pearl-like shape, aging as well, right, they become disconnected from each other and they no longer communicate and sense, and that's when you get all this dysfunction happening.

Well, I want to be respectful of your time here, but I want to just have one last area.

Here we touch on how we evaluate mitochondrial function.

There aren't a lot of good tests for it now, and you guys have come up with something new on that, maybe.

What are the problems with mitochondrial testing and what does your test do compared to what else is available out?

there, yeah.

So I mean it's been restricted mostly to research labs like ours where we have really sophisticated equipment where we can measure deep mitochondrial functionality at the different complexes.

The standard model is a muscle biopsy.

You have direct tissue from someone, but you have to extract it from someone, right?

So you go into a clinical setting and we do lots of these on campus.

We're involved in five-year projects where we're collecting samples from hundreds of people at different time points.

You numb the leg up it's a gigantic needle that goes into the leg and you pull the needle out and muscle comes out.

It comes to my lab.

We then spend the next six to eight hours analyzing this in excruciating detail, and so we can do typically two if on a good day maybe three muscle biopsies in terms of the analysis.

So there's no way to get throughput with this right, and the needle is a scary thing to go under.

I thought, since we were doing a lot of these, that I would put myself under the needle and actually go through with this, and I chickened out.

I couldn't do it.

I can't, there's no way.

So we were involved in a series of studies with NASA where the big challenge was we can only give you blood.

You tell us how to measure mitochondrial function, and so what my brain came up with was this idea of we're creating an environment in our body that's captured in blood.

Right, there's exosomes, proteins, metabolites, other factors that are secreted, that are sitting there, that create who and what we are.

Every one of your cells is bathed in that environment, and that environment then creates a metabolic phenotype, and so we really think that the metabolism of a cell is driven by the environment it's existing in.

And so the supposition for this NASA screen was could we, since we have blood from these twins at different time points in their spaceflight the year in space versus year on ground with the monozygotic twin could we use that environment that was captured in their blood and transfer that environment in an adoptive way to a cell type that we can manipulate in our system?

And so we could then pattern essentially the human body with cells onto this plate.

We could transfer the blood environment which every cell is seeing onto these cells and predict and see where the mitochondrial stress would happen.

And so we were able to basically figure out that certain systems in space would be impacted by this in terms of their energetics and mitochondria.

So we've now adopted this on a commercially available test called MeScreen, where anyone with a finger stick a couple drops of blood shipped to us in a dry sample and we can measure all kinds of things about your mitochondrial biology based on this adoptive transfer experiment, and the data we're getting is just insanely amazing, right?

Every person is unique and their mitochondrial signature is unique based on the life that they're living, and we're able to guide them to maintain that life if it's a resilient mitochondrial biology, and we're able to guide them to maintain that life if it's a resilient mitochondrial biology, and we're able to help guide them to say these are some defects that we're seeing that you may want to think about certain ways to talk to a physician to make marker and changes in this right.

So it gives us lots of insights and it's the one balance that all of us need in our body, right?

It's this energy currency, that this thing that our new test measures need in our body.

Right, it's this energy currency, that this thing, that our new test measures.

Wow, that's so exciting.

So, to recap then, the test you send in an at-home card which contains the sort of the extracellular fluid and all, and then you have cells there that are sort of standard cells that you bathe them in this personal, like my fluid from my test, and then you see how the cell responds and from that you can infer behavior about the mitochondria.

Yeah, yeah, that's so exciting.

I'm going to get one of those tests in a future program where we could talk about it some more.

That will be great.

Well, I'm so glad you're able to spend some time with us today, hemel, and thanks for that, and also thanks so much for all the work you're doing in this exciting area.

Yep, great seeing you.

Oh, also, do you have your social media links?

Or maybe tell them MeScreen, just verbally, how to find it?

Yeah, just go to MeScreencom and if you're interested, there's things that you can click on and find out more about our tests, and then we'll be at future events as well.

And so find us at some of these biohacker places and ask your physician, how can I measure my mitochondrial function?

And most of them will scratch their head and say I don't know.

Let's do an organic acid test.

This blows the organic acid test out of the water in terms of functionality and some structural data as well.

Excellent, I can hardly wait.

Well, thanks again and look forward to chatting again soon.

Yep, there's so much to learn about mitochondria and it.

Our knowledge is just exploding about those especially.

The fascinating part to me is how they're not just batteries of the cell, but how they actually drive chronic diseases and have amazing effects on our longevity.

So I and have amazing effects on our longevity.

So I want to thank Dr Hemal Patel for joining us today and sharing his amazing knowledge.

If you haven't claimed your VIP pass yet to access recordings, transcripts, mp3s and a must-have bonus, you can get it now by clicking on the button on the bottom of this page.

Remember when the event's over, the recordings and all the bonuses go away, so make sure you claim your VIP pass before it's too late.