For life to sustain itself, cells must do this important work themselves. It’s not like we can send in microscopic maintenance workers, mechanics, and security details to handle the dirty work from the outside. Not really, not yet. One of the most important types of biological maintenance is a process called autophagy.
Not so long ago, no one but the most hardened biohackers talked about autophagy. However, it has become a hot topic as scientists have made significant progress in understanding the ins and outs of autophagy over the past few decades. Now, anyone with an interest in longevity or intermittent fasting throws the word up in casual conversation.
But despite the widespread interest in autophagy, I’m willing to bet that the average person doesn’t understand it all that well. They probably believe that autophagy is desirable, and they may know that intermittent fasting will deprive them of more of it, but that’s it. So today I will answer some FAQs about autophagy. what it is, how to induce it and where to be careful.
What is autophagy?
Autophagy. the word comes from the Greek for “self-eating” and that is a very accurate description. There are several different types of autophagy. What we generally mean when we say “autophagy” involves organelles inside the cell called lysosomes that “eat” — or rather use enzymes to break down — parts of the cell that are damaged. or are faulty.
The main purpose of autophagy is to maintain homeostasis within the cell – the smooth operation of the factory. This is a type of cellular recycling process that allows organelles, proteins, and other structures to be broken down and used by the cell for energy or to make new components. Lysosomes can also degrade pathogens that threaten the integrity of the cell.
What activates autophagy in cells?
Autophagy constantly functions to manage basic cellular housekeeping, but anything that threatens homeostasis in a cell will increase it. Lack of oxygen (hypoxia), DNA damage, infection, or cellular damage due to factors such as oxidative stress can all induce increased autophagy. The trigger we talk about the most is nutrient deficiencies.
Your cells are finely tuned to how much energy is available. They have many systems to sense if energy reserves are sufficient and to indicate when they are low. When energy is abundant, autophagy works in the background; but when your cells sense that energy is low, they go into maintenance mode and autophagy really kicks in. You can understand why that would be. In lean times, your cells need to be more frugal, using what they already have on hand. Damaged proteins and organelles for firewood and their parts to build new machines just makes sense, so to speak.
Some of the signals that indicate low energy availability and dial-up autophagy are low glucose, low insulin, low mTOR signaling, high AMPK, and high glucagon. It is no coincidence that these are the same biological markers that characterize the metabolic state of fasting.
The reverse is also true, when glucose, insulin, and mTOR signaling are high and AMPK and glucagon are low, autophagy is inhibited. (By the way, this is why we say protein intake breaks his fast. Because when you eat protein, especially the amino acid leucine, you activate the mTOR pathway and decrease autophagy.
What roles does it play in the body?
By maintaining homeostasis and preventing cell damage, autophagy promotes the health of all your tissues and organs. Its specific effect depends somewhat on where the cells in question are located.
In the liver, autophagy is initiated during fasting, converting proteins into amino acids that can be used for energy production, thus maintaining whole-body energy levels even in the absence of food input.
Autophagy in muscle enables us to build strength and endurance when we exercise. Muscle damage is a hallmark of exercise and is important for the adaptation process, but without autophagy, muscle could not recover from said damage.
In the brain, autophagy helps clear waste and debris that would otherwise accumulate in neurons and lead to cognitive decline. Scientists are actively working on developing strategies to regulate autophagy in the brain as a way to prevent and treat neurodegenerative diseases like Alzheimer’s and Parkinson’s;
So autophagy is always desirable, right?
Not so fast. I see many people out there who undertake extreme fasting regimes or other biohacking strategies for the sake of maximizing autophagy. This seems counterintuitive given that we don’t know if more autophagy is necessarily better. In fact, we know there are times when this is the case no.
There is evidence that unchecked autophagy can in some cases increase existing cancer. There is a fact that too much autophagy in the wrong place can be bad. There is a fact that many things in nature follow the Goldilocks principle. too much is bad and too little is bad. The “right” amount is somewhere in the middle.
At this point, we simply don’t know what “optimal autophagy” looks like.. We know it’s important, but scientists are still working to figure out when it’s good (probably for the most part) and when and under what circumstances it becomes problematic.
When does autophagy start? What are the signs that this is happening?
The biggest conundrum for those interested in optimizing autophagy is that we can’t really measure it. Scientists have identified various biomarkers that signal that autophagy is occurring, but they are not the types that we can see in real time in a fasted walking human. There are still no continuous autophagy monitors slapped on the back of our arms to tell us how much autophagy is happening in our cells.
Instead, probably the best proxies we have right now are the metabolic markers that indicate our body is in a fasting state: low glucose, low insulin, high ketones, high glucagon. But here again we have a measurement problem. With the exception of glucose, we cannot constantly control these variables. And even if we could, and I expect continuous ketone and insulin monitors to be coming soon, we still don’t know exactly what we’re after.
The bottom line is that we can only conclude that autophagy occurs because we expose our bodies, and therefore our cells, to desirable, adaptive stressors. T:hat is about what we have to go on.
How to induce autophagy?
I just finished saying that we can’t control autophagy and that it’s not always good, but that doesn’t mean we don’t want to induce it. We do. We should. And the way we do that is by engaging in the kinds of behaviors that we talk about here all the time. Fasting and exercise, both high and low intensity, are among the most important, but there are others. Anything that stresses a cell is likely to trigger autophagy.
What to do with this information?
This cannot be emphasized enough. Autophagy is a long game, a lifelong pursuit, achieved through regular doses of exercise and not overeating every time you sit down to eat. Doing epic seven-day fasts every month, making sure you end each day with fully depleted liver glycogen, never consuming more than 20 grams of carbs per day; these strategies may be “effective” but obsessively trying to achieve a “perfect” level. Persistent autophagy is not a problem and is likely to activate or induce neurotic behavior.
Autophagy mostly happens when you just live a healthy lifestyle. Be active. Go hard every now and then. Sleep deeply. Restore well. Don’t eat carbs you don’t need. Sometimes ketosis is achieved. Do not eat more food than you need.
Start with those basics. Once they’re nailed down, and all caveats aside, I find it helpful to do a big “autophagy session” a few times a year. This is what mine looks like.
- Do a big workout that includes strength training and sprints. Very intense bursts. This will trigger autophagy.
- Fast for a few days. This will further stimulate autophagy.
- Stay busy throughout the fast. Walk as much as possible. This will really boost fat burning and get you into ketosis quickly, another autophagy trigger.
- Drink coffee throughout Lent. Coffee is a good stimulus for autophagy. Decaffeinated is fine.
I know people are often skeptical of the use of “Grock logic”, but it’s likely that most human ancestors experienced similar perfect storms of deprivation-induced autophagy at some point. They followed an animal for several days and came up short. Along the way, various stimulators plucked from the land were biting. They walked a ton, ran some, and lifted heavy things. And then they ate.
If you see yourself aging well, you’re on the right track. If you’re not progressing from insulin resistance to diabetes, if you’re maintaining and even building muscle despite qualifying for a blue plate, if you’re thinking clearly, I wouldn’t worry.
That’s it for today folks. If you have any other autophagy related questions, leave them below and I’ll try to address them all in future posts.
Thanks for reading.
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