#289 Dr David Sinclair Protein Speeds Up Aging - My Reaction and Analysis

Siim Land (0:00)

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So the first clip we're gonna play is gonna be actually his own new podcast which I recommend you to check out, Lifespan with Dr. David Sinclair and in his with his co-host they basically go through their book that they wrote together and yeah we'll just skip to the clip where he talks about how basically mTOR and the protein can contribute to aging.

David Sinclair (1:14)

We have a little bit of an understanding now how Sartuins are turned on by fasting.

We talked about two other classes of longevity genes in the first episode, mPOR and AMPK. Do you want to go really briefly through how these genes are impacted when we restrict calories when we fast?

David Sinclair (1:31)

The first one is mTOR, which stands for mammalian target of Rapamycin, the drug Rapamycin. We talked a little bit about it in the last episode, but let's refresh everybody's memory.

This is a protein complex in cell that registers amino acids. When you have a lot of protein in a big steak, it's going to activate this mTOR protein complex that allows the cell, causes the cell to build things. It's one of the reasons eating steak allows you to build more muscle, but that's not a recipe for longevity. What we know from many animal studies, even in yeast, if you downregulate the activity of this mTOR protein complex, you get longer life.

Why? Because it's activating a process called autophagy, which recycles proteins. So when you're hungry, this autophagy will get all the old proteins, put them in the recycling bin, and then bring them out as fresh proteins. And that seems to be really important for longevity. In fact, even if you just inhibit mTOR and stimulate autophagy, that's sufficient to extend the lifespan of flies and even mice by dramatic amounts, even 30%.

Siim Land (2:21)

So let's kind of analyze it a little bit. mTOR, the mammalian target of rapamycin, protein complex regulates growth pathways, regulates things like muscle growth, regulates things like nerve cell growth, as well as cancer cell growth and fat cell growth. So yeah, there are some benefits to having mTOR, but there are also some negative side effects to mTOR. And there are a lot of studies in many species showing that mTOR is kind of crucial and central to the aging process. If you have overexpressed mTOR or it's like dysfunctionary, expressed some sort of genetic mutations, then those animals die sooner, they get cancers and tumors. Whereas if you inhibit mTOR, then they live longer and they're healthier. So one reason for that is because mTOR inhibits the process of autophagy that recycles the cells from different kinds of old material.

And mTOR signaling also makes everything grow and you may develop a cancer sooner because of that. And so there is a lot of truth to that, that the mTOR complex is related to kind of aging, it's a central regulator of lifespan and aging. Many studies have found that and even like suppressing mTOR, inhibiting mTOR in humans with like rapamycin and these different kinds of drugs, that has been shown to be beneficial for the immune system and just general longevity. There's no human studies that mTOR inhibition is going to extend your lifespan, but there is animal studies and there is studies that it improves some aspects of health, like just health span, so to say, the better immune system function and that kind of thing.

So if we look at this graph from the study that I just showed you, then you can see mTOR C1, the complex one that is regulated by feeding and fasting cues. Basically if you're fasting, then you suppress mTOR and you're going to go into this more state of increased autology. If you're eating, then you're going to stimulate mTOR C1 that leads to anabolism and growth. So excess growth will just accelerate the aging process and even like cellular senescence increases. The senescence, which is describing the zombie cells, cells that aren't like with any function, but they're just staying there and spreading inflammation, that is increased by also mTOR C1. So you don't want to be having mTOR C1 activated constantly. The problem is that chronic mTOR inhibition can also be bad, can cause like muscle atrophy, muscle loss, can reduce beta cell proliferation. So to say your pancreas will produce less insulin, you become slightly insulin resistant because of that reduced adipogenesis, which is a good thing that you're not really growing fat cells, but you're not really growing muscle cells either. So there is a balance to it.