Transcript for:
mTOR Inhibition and Longevity Insights

You've heard of autophagy before. To really understand the perspective that mTOR inhibition promotes longevity, autophagy is in the middle of those things. So if you're looking at this in a linear way, inhibiting mTOR leads to longevity or the organism living longer. By inhibiting mTOR, you enable autophagy to occur.

That would be a critical mediator between these two things. Now, autophagy... I hate to bring in a new term with a new definition. You probably know it already, at least at a superficial level. It is at a superficial level, just the idea that the cell is renewing itself, that it is breaking down its older components.

You know, it's rebuilding its mitochondria. It's rebuilding its lysosomes. It's rebuilding its endoplasmic reticulum.

It's renewing its own membrane. You know, for example, that's the idea when it comes to autophagy, that a cell is able to recycle its parts. and thus keep its parts in sort of useful or functioning, if you will, and that allows the organism to live longer, to survive longer.

Okay. Now, with all of that having been said, let's move into rapamycin itself. As a reminder, mTOR, this critical mediator that wants a cell to grow, but thereby perhaps putting it on a clock, making it have a bit of a shorter lifespan, as the theory goes.

It is named after, mTOR is named after the drug, mammalian target of rapamycin, like I said earlier, M-T-O-R. So it's named after the drug. It was identified because it was identified as the target of this drug.

Now, why are some people so enthusiastic about it? It's because the animal evidence is quite convincing. Animal studies show that rapamycin extends life by up to 60% in these animals, which is absolutely a mind-boggling amount of time. Um, and any of these claims I'm making, you can just look in the show notes to get some of the references. So that that's really naturally you would look at that data and make a lot of very positive conclusions.

Um, it's no surprise that by inhibiting mTOR rapamycin has been shown to enhance autophagy. So you're helping the cells clear out their older parts and you have a bit of an anti-aging effect as the theory goes because of the activation of autophagy. which is able to occur because of the inhibition of mtor and mtor doesn't want autophagy could be viewed as a wasteful process you're recycling parts mtor could say i don't want to waste energy i want to be storing energy that may sound a little familiar if you've heard me discuss some topics on metabolism before there's a particular hormone that could describe that could be used to in that same way you know thematically saying to a cell, I don't want you to waste energy.

I want you to store it. We're going to revisit that hormone in just a minute. I'm a basic scientist.

I, my laboratory is literally right down the hall from where I am right now. I am conducting basic science research all the time. Being in meaning that I am seeking out, I'm seeking the mechanism of certain events within cells, this or within organisms. And so in my lab, we commonly use cell cultures, you know, growing cells in a little Petri dish.

And we commonly use animal models too, rats and mice. It's just because one reason why, because we can perfectly control for every variable. Now, why am I bringing that up? We also do human work too, but that doesn't happen in this building. Why do I mention the animal work in my own experience with it is because of what I said, you can literally control every variable.

These are not free living animals. They're not animals that are encountering any challenges. They encounter no, they live in absolutely, totally sterile environments. That's going to become very relevant as we get to some of the negatives of rapamycin in just a bit.

Like I said, they have no physical challenges. They exist. They spend their lives in a very, very comfortable space.

They don't need to use, they don't need to run away from any threat. They don't have any. They don't have any physical challenge. I guess I can just put it like that.

That then creates a point of concern as we try to take the animal studies and then extrapolate and apply those data to humans. That is what I consider to be an essential and oft overlooked consideration when it comes to those who are advocating the use of rapamycin for human longevity. But also, let me just say, there are no human studies that show that rapamycin, that even hint, that even can be. extended to show that rapamycin extends lifespan or prevents age-related diseases.

Nothing, not a single human study can show that. And that's because you cannot conduct longevity research in humans. It's impossible.

You cannot put humans in an enclosed space throughout their entire life where you can control every variable like we can do with the animals. Now, the nice thing about using that in animals is that it does let us eliminate variables. But these are variables that cannot be eliminated when it comes to human research. So let me just state that one more time so that you can have some of the same cynicism that I do when it comes to those who advocate the use of rapamycin for human longevity. It is based on no solid evidence in humans whatsoever.

It's only extrapolation from animal studies or correlation.