#443 Physionic on Longevity, Autophagy, Supplements, and More

Nicholas (0:00)

I'll just put it this way, I'm very hopeful for Rappamycin. I think if it's used correctly, it will end up showing that it has some pretty profound effects on longevity and potentially on health span. What do you want out of your life? You can't win it 100% everything, you kind of have to play this balancing act. You can't go extreme one way and still get the extreme of the other as well. This is tough, this is one of those questions where it's like make or break if a person is going to continue listening to you or not.

Siim Land (0:32)

Nicholas, welcome to the show.

Nicholas (0:33)

Hey, welcome. I'm really happy to be here.

Siim Land (0:37)

Yeah, I'm excited to also have you on the show. You have a great YouTube channel. And yeah, you have like a lot of very interesting videos about different new studies and new supplements and just longevity and science in general. So yeah, like I find it very useful on myself to kind of browse a lot of the videos that you have.

Nicholas (0:59)

I can say likewise. I mean, I know you've got a ton of content out there dissecting the science on, especially longevity in the longevity space. I've watched several of your videos. I really like them.

Siim Land (1:09)

Yeah, like likewise. But your specialty in a lot of ways is alzalfajim, which is something that was very popular, you know, something like five or four years ago. It still is. But that was like when I made a lot of my own videos back then about that topic. And it got like a lot of views. And it was like this massive kind of buzzword almost back then. But you're an actual like researcher of alzalfajim. So yeah, how did you like get into researching that specifically?

Nicholas (1:42)

So I got into researching autophagy in the lab throughout my PhD. So I was doing, so I did a undergrad work in mitochondria specifically in like bioenergetics and metabolism. And then I got into a master's program and I was still doing mitochondria and bioenergetics. And then when I went for my PhD, the lab that I joined, I brought my bioenergetics experience and brought that to this lab. And this lab was very focused on mitochondria and autophagy. And it's especially a particular type of autophagy called mitophagy, which I'm sure you've discussed before, which is just autophagy of mitochondria. It's just a fancy word for that.

Siim Land (2:25)

Right. And I guess we can start with what is autophagy. There's a lot of different definitions of it out there. And of course, there's dozens of different types of autophagy out there. But as the umbrella term, what does it actually describe?

Nicholas (2:43)

Yeah, autophagy is just...

So, the word itself indicates what it is, right? It's auto, so you're basically consuming self. And that's essentially what it is. It's just this mechanism that we can obviously get into more details on it. But this mechanism by which your cells are able to take up different proteins and lipids and organelles and just destroy them and just eliminate them for a number of different reasons. But that's the simplest explanation. Although, like you said, there are many different types of phages, like xenophagy or autophagy or mitophagy. And there's different versions that ultimately fulfill different functions, but they all operate very similarly.

Siim Land (3:27)

Yeah. Yeah, I was like reading about that. Then you have like virophagy and bacteriophagy, and like you said, xenophagy and agrophagy, and yeah, almost like phagy for every kind of organ in the body.

Nicholas (3:41)

Yeah. Yeah, definitely. Exactly.

Siim Land (3:44)

But how does it relate to longevity? I know one of the main, let's say, selling points or the ideas behind Atafati was that it's important for longevity to remove these dead cell parts that accumulate during aging.

Nicholas (4:00)

Yeah, so there's, you could just that one question, which is a really good question. That one question could probably be filled up with like an hour's worth of content just because the sheer complexity of what happens. So, but I'll give you just like one brief way that Atafati strongly contributes to not just lifespan, but health span as well. So one thing that happens with aging, especially let's say around mitochondria, is that you can experience what's known as proteotoxicity, where you get this accumulation of dysfunctional proteins or mistargeted proteins. What do I mean by mistargeted proteins? Is your cell will produce proteins, and they actually have tags on them that tell or biochemically tell the cell where to place them. So they should be in different compartments of the cell so that they can fulfill their particular function. So think of like you wouldn't want a lifeguard at, I don't know, in a sauna, or you wouldn't want a lifeguard as a police officer. You need to put these different functional proteins, these different roles in their specific area. So there can be mistargeting of proteins, which happens with aging as our DNA structure gets damaged and whatnot that ultimately leads to these proteins that may be functional, but their targeting is mislabeled to the point where they end up going to the wrong areas within the cell. So they can accumulate, which is called proteotoxicity, around these organelles like mitochondria, which ultimately then leads to autophagy to come in and eliminate either the mitochondria or eliminate these aggregates of proteins that are just kind of stuck within the cell. And once you've eliminated those, then you've cleared up space and allowed the cell to potentially produce the correct protein and target it to the to the correct spot. And that's just one example. I mean, there are many, many others.