Autophagy Beyond Fasting: How Protein and mTOR Affect Cellular Cleanup

Two people can live nearly the same life and age completely differently, and a lot of it comes down to a single switch inside your cells that you can turn on today. That switch controls a process called autophagy, and it almost always comes up alongside fasting. But fasting is just one way to activate it.

In fact, some of the most powerful triggers of autophagy don't involve skipping meals at all. And the word autophagy means self-eating. Think of it like a cleanup crew that patrols your body around the clock, and if it finds cells that are broken or pre-cancerous, it clears them before they can turn into cancer.

It's one of the most powerful ways your body protects itself, and the discoveries that explain how autophagy works earned the Nobel Prize back in 2016. And there are a surprising number of ways to activate this process. Most of us are just shutting them off without realizing it.

Flip them back on, and your body gets back to doing what it's built to do, repairing itself and aging slower and catching diseases and cancer long before they even have a name.

So in this video, I'm gonna walk you through these switches one at a time, and we'll start with the one that almost everyone gets backwards.

And then we'll talk about a few everyday things that turn it on.

Many of them are much easier than fasting and don't take a long time.

And then at the end, I'll go over the nutrients and supplements that your cleanup crew needs just to run, including one that about half of adults in the US don't get enough of without realizing it. And if you're new here, I'm Dr. Leonard Kim. I'm a double board certified physician,

and on this channel, my mission is to give you the science and the practical tools to not only live longer, but to feel better today. And as always, even though I'm a physician, I'm not your physician. So please talk to your doctor before making any changes to your health regimen, as this video is educational only and not

medical advice. All right, let's get into it.

So switch number one is the one that almost everyone gets backwards.

There's a master control in your cells called mTOR, and it does one of two things. It basically decides whether your cells spend their energy building or cleaning house. And as soon as building materials show up, it switches into build mode, and then the cleanup crew shuts off.

And this mTOR pathway is one of the most commonly overactive pathways across human cancers. So dialing mTOR down and flipping on the cleanup crew brings it back on.

It pushes against the very signaling that fuels a lot of cancer growth. So what does your cell actually see as building materials? Well, surprisingly, it's less about calories in general and more about amino acids, uh, the building blocks of protein.

And one of these amino acids, leucine, is the main activator switch, while the other amino acids prime the process, but they're not as dominant.

So when leucine shows up, mTOR kicks into build mode, and the cleanup crew shuts off. And leucine is most concentrated and most usable in animal protein, things like whey and meat and eggs. And it's not just how much leucine is in each protein. Uh, the key word here is usable.

Because many plant proteins still pack quite a bit of leucine, but it's more difficult to digest, so less of it gets absorbed to flip that mTOR switch. So a whey protein shake dials your cleanup down faster and more completely than a bowl of beans.

Now, this begs the question, is protein bad?

Well, no. Protein is one of the most important nutrients that you can eat, especially as you get older, and you need it to grow and protect your muscles, which will protect your bones.

And there's also nothing wrong with animal protein.

Gram for gram, it's one of the most nutrient-dense foods that you can eat that's chock-full of useful vitamins.

How you wanna approach this is cycling. So keeping protein high most of the time, but easing off every once in a while. So one day a week, make it a lower animal protein day. So you'll lean on plant protein like beans and lentils. Uh, you're still getting plenty of protein to protect your

muscle. It's just lower in that usable leucine that flips mTOR on. And then the other six days, you just get back to your usual protein.

Now, the next switch flips on the same system, but through a completely different pathway. And whether it works for you, it all depends on the bacteria in your gut. It starts with a compound called urolithin A. It's one of the strongest triggers that we know for a kind of cleanup called mitophagy, which is autophagy aimed at your

mitochondria, um, the power plants inside your cells.

And this is a very important process because old and damaged mitochondria, they can stop working well, and they leak harmful molecules, which can damage the cells around them.

And on top of that, precancerous cells also rely on unhealthy mitochondria to survive, and mitophagy helps clear those out.

In randomized trials, urolithin A improved muscle strength and endurance and markers of healthy mitochondria.

And in your trial, also found improvements in aging immune cells.

Now, no one's tested whether it slows down chronic disease or it actually lowers cancer risk in people, but the cleanup it drives is real, and we can measure it. Now, there's a catch to this.

Urolithin A isn't actually in any of the foods that we eat.

Foods that we associate w- with urolithin A, um, things like pomegranates and blueberries- Walnuts and berries, well, they give you the raw ingredients, but your gut bacteria have to turn this into urolithin A, and only about 40% of people carry the bacteria that can do this. So two people can eat the exact same pomegranate, but

only one of them turns this into this useful compound, but the other one makes almost none. Same fruit, but completely different results. So we still wanna eat the right foods that provide the raw ingredients, pomegranates and walnuts and berries.

But since not everybody carries the right bacteria, this is one place where a supplement may make sense.

Taking urolithin A directly can skip the whole gut bacteria lottery.

Now, one important side note is there's not a whole lot of human data here. Uh, most of the studies are smaller and shortened duration, and these studies measured biomarkers and short-term physical endpoints, like muscle strength and endurance and aerobic tests, but not long-term disease or cancer outcomes.

And so the question is, what can you do after those meals when a walk just isn't gonna happen? Now, this is where we get back to the muscle in your calf, and it becomes a really useful tool. That muscle is called the soleus,

and it sits in the back of your lower leg underneath the bigger calf muscle that you can actually see, and it's tiny. We're talking about roughly 1% of your body mass.

So how does one tiny muscle produce a 52% drop in blood sugar?

Well, gram for gram, researchers found that the soleus could work at roughly eight times the metabolic rate of your leg muscles during the moderate walk.

And part of the reason is that the soleus is built for a very different kind of work. It's packed with slow oxidative muscle fibers, and these aren't the fibers designed to give you one huge burst of power.

They're designed like that Energizer Bunny that just keeps going.

In contrast, think about doing squats. You're using your quads and your glutes, some of the biggest muscles in your body, and that's great for pulling glucose out of your blood.

But as we keep doing more squats, our legs will eventually start burning, and we're gonna have to stop. But the soleus is almost built for the opposite job, a small amount of work, but they can keep going for a very long time. And there's actually another whole separate reason it can do that.

So normally, when your muscle is working, one of the fuels it uses is glycogen, which is basically a carbohydrate already stored inside that muscle.

It works like a little fuel tank. Uh, it's right there ready to use, but there's only so much of it before it gets depleted.

But when researchers had people doing these soleus pushups, this muscle barely touched that stored glycogen. Across hours of continuous work, glycogen only supplied about 4% of the energy used.

So instead of burning through its own stored carbohydrate and glucose storage, the soleus was relying heavily on the outside fuels coming from the blood. And that mechanism explains how that little muscle can go for so long, and it really explains those remarkable numbers in that study, with

blood sugar being down 52% and insulin down 60%.

Now, these are the numbers that you've probably seen making rounds online and in other YouTube videos, but there is one important part that tends to get left out. In that study, to get those numbers, they were doing that exercise for three hours. They kept the soleus working throughout the entire

three-hour glucose test. And when you look at the other work from this group, that duration appears to be pretty important.

They didn't start seeing a significant increase in glucose uptake until about 30 minutes in. And when the contractions stopped while glucose was still elevated, blood sugar started moving back toward what they saw while just sitting.

So that 52% number is real, but it came from keeping this muscle working for hours and not minutes, and that's the trade-off. A lot of muscle can do the job in three minutes, but 1% of your body, like the soleus muscle, well, that needs a lot longer.

But that doesn't mean you need to sit there doing this for three hours straight to get anything out of it. So with that framing, the honest take is this is not something we do for five minutes and then check it off your list.

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