← Biohacking Beauty: The Anti-Aging Skincare Podcast
Biohacking Beauty: The Anti-Aging Skincare Podcast
The Overlooked Side of Autophagy Causing Aging - Part 1
00:26:17
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- [00:06]
A
What if I told you that your skin could literally eat itself young?
- [00:12]
B
I would probably say,
- [00:17]
A
because there's a process inside every one of your skin cells and actually every one of your cells when it's running well, at least. Which breaks down the damaged parts and. And builds something even better with the pieces. I call it the Phoenix process. If you rises from the ashes. Yeah.
- [00:38]
B
And I think when it stops running, well, that's when people have the skin they have after 40s.
- [00:45]
A
Yeah. This basically, you know, which is basically a cell that's been making copies of damaged copies of damaged copies of damaged copies. Sometimes I also say, you know, like we're. This is a meat suit. Right. If you put meat in the fridge without, you know, any maintenance process, just meat goes bad pretty quickly. If you put it out, by the way, we are not in the fridge. So if you put it out goes bad even. Even faster. That's what happens, let's say without that process.
- [01:13]
B
I know every time you do this analogy, all of your analogies today are not very appealing.
- [01:18]
A
Yeah.
- [01:19]
B
Well, I'm Anastasia and I'm here with my co host, Amitai Eshel.
- [01:26]
A
Eshel, that's me. Anastasia Khloja. That's her. We are, of course, the.
- [01:31]
B
The founders of Younguss Skincare.
- [01:33]
A
Yes.
- [01:33]
B
And the hosts of this very biohacking beauty podcast.
- [01:36]
A
You know the word founder, I always think about it. Sounds like we found Yungus anyway.
- [01:42]
B
Yeah, Yungus found us.
- [01:43]
A
Yes, that's true. This is the biohacking beauty podcast.
- [01:48]
B
Yes. And everything we were talking about until now is autophagy. So it won the Nobel Prize in 2016. And we are going to spend the next hour or so showing you exactly what it is, how it rebuilds your skin and what to do every day to turn it on.
- [02:05]
A
Yes. And if you're watching this on the wonderful YouTube, this is our new. Our new home studio.
- [02:15]
B
It's still work in process.
- [02:17]
A
Yes, exactly.
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B
So don't judge it yet.
- [02:20]
A
Yeah. But I hope it's going to make us feel more comfortable. Anyway, let's get into it. Autophagy. So, Anastasia, let's start in the beginning. Okay.
- [02:32]
B
That's usually a good place to start.
- [02:33]
A
I think most people, when they hear the word autophagy, they just default to the, you know, something that's connected with fasting, some positive effect that happens when you fast. And that skips, I think, a very large part of the story. So how about you walk me through autophagy, what it means.
- [02:51]
B
Yeah. Where it comes from, for sure. So the word autophagy, it Comes from Greek and auto means self and phagi means eat. So self eating, basically. In 1963, a Belgian scientist named Christian de Duff coined the term, when he coined the term when he realized cells had a way of digesting their own components inside little membrane bound compartments called lysosomes.
- [03:22]
A
So Duduf named it in the 60s. Then we're basically not.
- [03:30]
B
Almost nothing happened.
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A
Yeah, Nothing happens for 30 years, right?
- [03:32]
B
Yeah. So the reason almost nothing happened, I mean, the scientists were working on it, there was very small amount of papers being written about it. And the reason the process, the progress was so slow is because the machinery was invisible. So no one knew which genes ran the process. And then in the early 90s, Yoshinori Osumi, a Japanese cell biologist working with baker's yeast, was actually determined to figure it out.
- [04:01]
A
So he was basically working in the kitchen. Yes, that's like baker's yeast. The same bake.
- [04:07]
B
Yeah, yeah, yeah, yeah. So many women bake their own bread. There you go.
- [04:10]
A
That's the experience. They don't know that they could have won the Nobel Prize.
- [04:14]
B
Oh, yes, yes. And the reason he chose yeast is because the yeast cells are very simple, they reproduce fast, you can knock out genes one by one. So, so Assumi ran a genetic screen. So he identified 15 genes that are essential for autophagy in yeast and he called them ATG, basically autophagy related genes. And in 2016, he won that same Nobel Prize we talked about, which is well deserved.
- [04:42]
A
So the Nobel Prize was actually rewarded to him for work done mainly in yeast.
- [04:47]
B
That's correct, yes. And what's really fascinating here is that the same ATG genes exist in humans, in plants, in every eukaryotic cell, basically. So they're highly conserved through evolution. And that also means that they're very, very important for our biological processes.
- [05:06]
A
Yeah. It reminds me, you know, when we kind of debunked that guy that was talking about vampire exosomes and he's like, well, you know, some of the genes they're talking about, they're talking. They were using a software that was talking about gene in mice.
- [05:22]
B
And you know, in the last time I checked, we are not rodents.
- [05:25]
A
Yeah. Which I like this sentence, by the way. I mean, I just know, I just
- [05:30]
B
imagine a guy very Gen Z, very clickbaity.
- [05:32]
A
I'm just imagining a guy over and over again, checking for rodents. But the main thing is that conservation of genes is one of the most. It's a green flag for a gene, if you will.
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B
It means the gene very important.
- [05:47]
A
Is important across species, if you will. So the fact that we can trace them in very simple life forms and they kind of conserve themselves until today is a really important thing. If anyone's super interested, the Selfish Gene by Richard Dawkins is an incredible book to kind of understand that process. Okay, so how about you break down the process, how the process actually looks like? This is supposed to be a deep dive. So how does it look like in a cell? In a fib. Fibroblast in someone's. I'm a fibroblast in someone's cheek.
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B
Okay, yeah.
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A
Autophagy activates. Now what is happening?
- [06:29]
B
Yeah, so inside you there is a damaged mitochondria, for example, mitochondrion, the one. And it's licking reactive oxygen species. So the way autophagy happens, a membrane starts to form around it, a flat sheet that curls, wraps and eventually seals in a double membrane sphere. So that sphere is called an autophagosome. It's a stellar equivalent of a garbage bag.
- [06:56]
A
A garbage bag that collects its own
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B
trash that knows what to grab? Yes. Basically it's a very modern garbage bag, Very AI driven, I don't know, robotic garbage bag.
- [07:08]
A
I just imagine the people today with the EU examples. I just imagine the people that need to pick their own dog's poop. So they put the bag on their. Then they grab.
- [07:17]
B
Yeah, yeah, something like that. And so that selectivity, it happens different ways. So normally it would be a special protein that is kind of like tagging the cargo that needs to be picked up. So one of the most important proteins will be P62 and that can flag damaged stuff for engulfment. Another system uses proteins called pink1 and parkin, which we'll talk a little bit later, more about, to specifically target broad in mitochondria. That what that process of targeting and recycling. Mitochondria has actually a separate name which is called mitophagy, which is part of
- [07:59]
A
autophagy is just like.
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B
Like a sub category mitochondria.
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A
Yeah, so we have macro autophagy, we have micro, which is like, you know, that bulk garbage bag process. And we have these specialized subtypes. Right. So we. We have mitophagy for mitochondria. What else?
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B
Yeah, so there is also chaperone mediated autophagy, cma, which picks up individual proteins with a specific five amino acid sequence and delivers them one at a time into the lysosome.
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A
Through which is the garbage bag.
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B
Yes, yes. Through a special receptor and microautophagy, where the lysosomal membrane itself just Invaginates and sucks in material directly inward. And then it has very basically acidic, you know, liquids there. And it just, you know.
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A
Yeah, processes.
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B
Processes, yeah, yeah.
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A
So we have three flavors. We have macro, micro, and cma.
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B
Cma, yes. So for skin, I think microautophagy and mitophagy are the most clinically relevant.
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A
Okay, so we've got my autophagosome wrapped around the damaged mitochondrion. Okay, that's where we're at. What next?
- [09:15]
B
Yeah, so then the autophagosome fuses with a lysosome. And so the lysosome is that organelle I told you about that has a lot of acidic enzymes. And then inside those enzymes, there will be proteases, lipases, nucleases. So they break down.
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A
You know, every time we hear an ace, it means it's gonna be breaking that down, right?
- [09:35]
B
Yes. And then. So proteases is for protein. So it's gonna break things down down into amino acids, individual amino acids. Lipases is folipids. So it's gonna break down things to fatty acids. So those building blocks then pumped back out into the cytoplasm, which is like a really key moment here.
- [09:56]
A
Yeah, it is, because first of all, it's. It's. You know, so much of the discussion is on feeding, you know, our skin, our body, whatever that is, and this is the body's. So the main processes in the body, actually, especially when the skin is concerned. We talk a lot about. When we talk about nad, we're like, hey, guys. Yeah, we're supplementing, we're giving you skincare with NAD precursors, all of that. But the real issue is, like, the bulk work. Is your body kind of recycling everything? Right. So that's very similar here. You know, we're talking about, are, you know, collagen peptides worth your money? You should take them. You shouldn't take them. Well, the most important is, like, supporting your body, taking older material and like, recycling them to those. Those, you know, materials that raw. Raw. Raw materials directly where the. Where they are needed again.
- [10:42]
B
Right, exactly. And a lot of the time when people think of autophagy, they kind of like, think of destruction, right? But you actually, it's. It's really not a destruction. It's recycling. You make new proteins, new membranes, new mitochondria out of the older ones. So the cell literally building its new self out of the old self.
- [11:04]
A
That's. That's really cool. It's not only cell, Right? So as we keep going back and forth it's like, also the parts, like, I really, you know, people care about collagen, so I bring it back to collagen. You know, you could think of a spring. Collagen is very similar to a spring or to glue. Right. And you could think of either or whatever you want to think about. But the spring that's been used a lot or glue that's been, you know, that, that. That the piece that connects. Pieces that connects together have been, you know, bent a lot. This becomes to fray. It becomes less elastic, both in the glue and the spring example. So you want a new spring or, you know, adhesive there. Right. This is, again, the body has a really hard time, like, getting those raw materials. It breaks down that, you know, I'll go with spring just so I don't have to go. But two examples at once. Breaks down that spring, builds a new spring that's way springier, way more responsive, flexible, et cetera. That's best case scenario, right?
- [12:00]
B
Yeah. Whenever I think of, like, forever young or, you know, a person that is aging really well or quote unquote, doesn't age, like, having that perfect process of autophagy, which obviously declines with age, would be a key part of it, like staying young because you just constantly renew yourself and, you know, you don't accumulate damage.
- [12:24]
A
Yeah, that's, you know, for a long time, people are trying to replace the. The buzzword anti aging for many reasons, by the way. Also, like, Amazon really doesn't like the word anti aging, you know.
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B
Really?
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A
Yeah. Yeah. And there are countries that anti aging is considered like, a drug claim. So the fact that, you know, you hear your favorite whatever fill in the blank saying, oh, I don't believe in anti aging. I get it. But it's more like, you know, the zeitgeist is turning away from anti aging because it's a problematic word to use. But I agree that within the.
- [13:00]
B
I think that people are. A lot of times, they just.
- [13:03]
A
They're looking for a new word.
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B
Yeah, they're looking for. Because they don't like anti. And they don't like, like, oh, I'm not fighting aging. I'm aging gracefully. And. And it's not everyone, but there is a subset of people that are like, let's change anti aging to pro aging. But they don't mean like, oh, I want to age faster.
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A
You know, that's.
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B
I'm just like, not. Not delusional about the fact that I'm aging. You know, like, kind of what is pro aging?
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A
I never understood that that means you're for aging. That's.
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B
Well, that's the thing that you can't,
- [13:33]
A
you know, you can't just change one word to a positive. You know, it's like, are you anti car crash? No, I don't want to be negative. Are you. So you're pro safety, you're not pro car crash.
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B
Yeah. Okay.
- [13:49]
A
So within this, these parameters, you know, longevity is coming in, but also slow aging. So we're, you know, slow aging is a real definition, is the real definition of what skincare can do. One of the pillars we're talking, we're going to talk more about that. But I think you know, exactly like the word anti. Many people within the longevity community I think feel that autophagy is like a very aggressive and it's kind of what we talked about now. Acids destroying cannibalism, something violent. Right. So this is important to understand what you're describing. What Anastasia is describing is more than a, you know, renovation crew. Right.
- [14:30]
B
I mean, yeah, there is always some level of autophagy happens in your body, like some basal autophagy. And like we talked about, the question is how efficiently it's happening and what do they pick up? Do they pick up and recycle the right stuff, like is it properly tagged or not?
- [14:48]
A
Yeah. Like we talked off air the other day in the car. They can be, there can be too much autophagy.
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B
Yeah. So who decides like if you're fasting non stop and you're just like on this pro autophagy lifestyle. Yeah. It will start breaking down your muscle, it will start breaking down the tissue you don't want to break down.
- [15:08]
A
Yeah, yeah. I think I'm going to make a short anti aging aging club. So again, who decides when to dial it up, when to dial it down? Normally in the world of biology we're talking about switches, right?
- [15:24]
B
Yeah, yeah. This is a really great question. So there are two master switches. One will be basically mtor and that's a mechanism. MTOR stands for mechanistic target of rapamycin. And it's a well fed state. So when there is lots of amino acids, there's lots of insulin, lots of growth factors around. MTOR is active and MTOR is signaling your body to build, synthesize proteins, grow. And that's imagine that's the process that is kind of like anti autophagy. So it turns autophagy off.
- [16:02]
A
Yeah, yeah. I, you know, many people describe atoph, sorry mtor like life is good, make more of me. Right. I like to describe it a lot as like you're imagine a lion, right? Because again, this is another thing that's being conserved across, you know, species. Think of a lion, you could have two states. You're the apex lion of the pride, or you could be like a younger or an older lion waiting on the sideline. Right. So MTOR activated is like apex line, you know, now I need to procreate, I need to take care of my pack. I need to be the strongest, biggest, most whatever. We need to grow, right? We need to be big, seize the day. You don't know what's going to come. Come back tomorrow. We're not about longevity right now. We're about being the strongest, the optimal right now, either way, again, more aggressive example. But that's what MTOR stands like an activated MTOR stands for, right?
- [17:02]
B
Yes, yes. I think this is a great example. It does to me have this very like male energy. Like, you know, like. Yeah, like an apex predator energy.
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A
Yeah. Big MTOR energy.
- [17:17]
B
Yes, Big MTOR energy. Yeah. Okay, so the other process, it's an opposition to mtor. It will be basically the switch. The switch, switch will be the ampk, and that's AMP activated protein kinase. So that's actually the switch that turns on when we are stressed for energy, like deprived of energy. So the cellular ATP drops and that basically turns on the amp, which in turn like AMP rises, AMPK activates and it says we don't have the resources to build and grow right now, so we need to clean the and extract the energy from what we already have. So AMPK then turns on the autophagy. And that's where we talked about this whole process that it finds older and maybe then functioning stuff.
- [18:11]
A
And so it's going to turn off MTOR as well, right?
- [18:14]
B
Yes, yes. And break it down to the pieces and start recycling.
- [18:18]
A
Okay, so if we think of a video game, it's like MTOR versus mpk, right?
- [18:23]
B
Totally.
- [18:23]
A
And you know, most people, or most people's cells rather in most of the developed world are stuck in permanent MTOR mode. If you, you know, I remember Benazadi, my friend Benazadi shout out to Ben Azadi kind of breaking down how often people eat during the day that they're constantly snacking. Yeah, that's basically.
- [18:46]
B
And there's no room for autophagy for sure. Yes. I mean, remember that in order for autophagy to get activated, you do need to have like a little bit of less energy, you know, so it. And that's why autophagy is often associated with fasting. You have to have those Windows when you're not eating to turn on the autophagy. So if you're always eating and snacking. Yeah, you're gonna, you're gonna silence your mpk. And then also for Mtor in particular, like if you not. And speaking of like Benazadi and why he's saying people are right now in our part of the world are more in this mode. It's. We're eating very protein heavy meals as well. So tell us, keep getting the signal. Build, build, build.
- [19:32]
A
Yes. And you're saying mainly, you know, you're saying protein heavy. You know, those who are listening, you're going to hear a lot about in the future about like longevity and leucine. You know, we have a friend with a company named Novos for example, Chris, we're going to have Ipsoning in on the podcast. They released like a protein bar which is leucine. It doesn't have leucine. And the main reason is what you alluded to is that there is a specific amino acid that MTOR reacts to more as far as feeling we're in a fed state. Right. So that's just to kind of gather things together anyway, kind of switching gear and talking about the skin, I think this is my mental model. You know, that's what skin aging or you know, as we said like slow aging really is. It's not that the cells have stopped working. Actually we might get to it, but cells working sometimes is the problem. Right. So it's not that cells stop working, it's that they've been told to build without being told to clean.
- [20:38]
B
Yeah, yeah, exactly. And there's. And what you're saying kind of was mapped into exactly what's happening in aged human skin fibroblasts. So there was a paper in 2018 in Experimental Gerontology and they measured autophagy markers in young versus old human fibroblasts. So the basal autophagic activity wasn't dramatically lower in old cells. Meaning that, you know, they still have autophagy going. The problem was that all cells were generating more damaged cargo and then the autophagy capacity wasn't scaling to match the demand.
- [21:15]
A
So the janitorial crew, the, you know, the maintenance crew stays at the same size, but the work, there's more mess comes up. It's like yangus. You know, we always have more and more work.
- [21:33]
B
Luckily our team has grown to match that.
- [21:36]
A
Yeah, yeah, that's true. But anyway, that actually is not true for young girls.
- [21:41]
B
Yeah, yeah, we're.
- [21:42]
A
If you're a superstar by the way, come work for us. But that's a different story.
- [21:46]
B
Yeah, sure.
- [21:47]
A
We're hiring, by the way, before we continue, we're switching things up and we're going to take a short break and we're going to talk about a. The fact that we want to give you a free product. We want to hire you if you're a superstar. Reach out to serviceanggoose.com but we also want to read the review and give you a free product.
- [22:14]
B
And what product will it be?
- [22:16]
A
It will be Blue Peptide Spray.
- [22:18]
B
Okay, let's do Blue Peptide spray.
- [22:19]
A
Yes, let's do Blue Peptide spray. The thing is this. So basically, reviews make sure that this information that as you can see is just marvelous and no one's talking about reaches more ears. So how does that happen? Reviews, people listening to this, but it allows us to just educate more. So we want to give back. So if you write a review, we read your review on air, we're going to send you a free product. This time it's going to be Blue Peptide Spray. Go ahead, Anastasia, read the review.
- [22:45]
B
Okay, so it says educational, practical and informative. I'm obsessed with this podcast. Every episode leaves me with at least one practical biohacking tip I can add to my skincare routine. Yangos is changing the way I think about beauty and longevity.
- [23:01]
A
Beautiful. Who's the person?
- [23:03]
B
Aima? Me. Music.
- [23:05]
A
Oh, the music to my ears. Anyway, so yeah, serviceangoose.com or DM us on Instagram and the product is on its way to you.
- [23:15]
B
So thank you so much for leaving the reviews and next time maybe we'll read yours.
- [23:20]
A
Yes. So getting back to the point, Janitorial crew stays the same size. Yeah.
- [23:28]
B
And the cleanup falls behind.
- [23:30]
A
It just becomes dirtier and dirtier faster and faster.
- [23:32]
B
Yeah. So you start accumulating. Actually, when that happens in the cell, a lot of times you start accumulating what's called lipofuscin. And it's a brownish yellow autofluorescent aging pigment and it's composed of oxidized lipids and proteins. That's often viewed as cellular garbage. High levels of it can impair cellular function, contribute to oxidative stress, and indicate age related diseases. Now, obviously we're talking about more of like when it happens in the brain, but it's, it can lead to amd, neurogenerate neurodegeneration. So that aging pigment and accumulation of it further clogs autophagic flux and it becomes a negative feedback loop.
- [24:13]
A
Yeah, that's the important thing. It's like not One, you know, it's not a natural process. One mistake, just like it makes all the. What's it called? Like a house of cards. Right. That everything falls at the same time. It's an accumulation of mistakes. Mistakes or damage breeds more malfunction and that breeds more mistakes.
- [24:37]
B
Yeah.
- [24:38]
A
So it's a compounding effect, if you will.
- [24:40]
B
For sure.
- [24:41]
A
All right, so that's the foundation. Right. Cells have a self cleaning system. It's evolutionarily ancient. It won a Nobel Peace Prize. And it's run by two opposing switches, which I actually want to think of as dimmers more than switches. But we'll talk about it later. Let's get into what that actually does in the organ that we care about most, which is the skin.
- [25:10]
B
Yeah. And I just wanted to say that now it's been 29 minutes, so I think this should be our part two, because that's at least 29 more minutes.
- [25:18]
A
Okay, great. So we can even keep this on air. Guys, listen, we want to make sure that this information is coherent, that you understand what we're talking about here. So that's going to be the end of part one. Stay tuned for part two and more amazing things.
- [25:37]
B
Yeah. In part two, we'll talk about how autophagy renews skin. So that will be much more skin specific information about autophagynous processes.
- [25:47]
A
Yeah. All right.
- [25:48]
B
Okay.
- [25:49]
A
See you later.
- [25:50]
B
See you in the next episode. Thank you for listening. Bye Bye, Sam.