Biological systems are self-maintaining. They have to be. We don’t have maintenance workers, mechanics, troubleshooters that can “take a look inside” and make sure everything’s running smoothly. Doctors perform a kind of biological maintenance, but even they are working blind from the outside.
No, for life to sustain itself, it has to perform automatic maintenance work on its cells, tissues, organs, and biological processes. One of the most important types of biological maintenance is a process called autophagy.
Autophagy: the word comes from the Greek for “self-eating,” and that’s a very accurate description: Autophagy is when a cell consumes the parts of itself that are damaged or malfunctioning. Lysosomes—members of the innate immune system that also degrade pathogens—degrade the damaged cellular material, making it available for energy and other metabolites. It’s cellular pruning, and it’s an important part of staving off the worst parts of the aging process.
In study after study, we find that impairment to or reductions of normal levels of autophagy are linked to almost every age-related degenerative disease and malady you can imagine.
Okay, so autophagy is rather important. It’s fundamental to health.
But how does autophagy happen?
The way it’s supposed to happen is this:
Humans traditionally and historically lived in a very different food environment. Traditionally and historically, humans were feasters and fasters. While I don’t think our paleolithic ancestors were miserable, wretched, perpetually starving creatures scuttling from one rare meal to the next—the fossil records show incredibly robust remains, with powerful bones and healthy teeth and little sign of nutritional deficits—they also couldn’t stroll down to the local Whole Foods for a cart full of ingredients. Going without food from time to time was a fundamental aspect of human ancestral life.
They worked for their food. I don’t mean “sat in a cubicle to get a paycheck to spend on groceries.” I mean they expended calories to obtain food. They hunted—and sometimes came back empty handed. They dug and climbed and rooted around and gathered. They walked, ran, stalked, jumped, lifted. Movement was a necessity.
In short, they experienced energy deficits on a regular basis. And energy deficits, particularly sustained energy deficits, are the primary triggers for autophagy. Without energy deficits, you remain in fed mode and never quite hit the fasted mode required for autophagy.
Now compare that ancestral food environment to the modern food environment:
Almost no one goes hungry. Food is cheap and plentiful, with the tastiest and most calorie-rich stuff tending to be the cheapest and most widely available.
Few people have to physically work for their food. We drive to the store and walk a couple hundred steps, hand over some money, and—BOOM—obtain thirty thousand calories, just like that. Or someone comes to our house and delivers the food directly.
We eat all the time. Unless you set out to do it, chances are you’ll be grazing, snacking, and nibbling throughout the day. We’re in a perpetually fed state.
The average person in a modern society eating a modern industrial diet rarely goes long enough without eating something to trigger autophagy. Nor are they expending enough energy to create an energy deficit from the other end—the output. It’s understandable. If our ancestors were thrust into our current situation, many would fall all over themselves to take advantage of the modern food environment. But that doesn’t make it desirable, or good for you. It just means that figuring out how to trigger autophagy becomes that much more vital for modern humans.
Here are 7 ways to induce autophagy with regular lifestyle choices.
There’s no better way to quickly and reliably induce a large energy deficit than not eating anything at all. There are no definitive studies identifying “optimal” fasting guidelines for autophagy in humans. Longer fasts probably allow deeper levels of autophagy, but shorter fasts are no slouch.
When you’re keto- and fat-adapted, it takes you less time to hit serious autophagy upon commencing a fast. You’re already halfway there.
With exercise-related autophagy, the biggest effects are seen with lifelong training, not acute. In mice, for example, the mice who are subjected to lifelong exercise see the most autophagy-related benefits. In people, those who have played soccer (football) for their entire lives have far more autophagy-related markers of gene activity than people of the same age who have not trained their whole lives.
In studies of acute exercise-induced autophagy, the intensity of the exercise is the biggest predictor of autophagy—even more than whether the athletes are in the fed or fasted state.
At least in mice, both caffeinated and decaffeinated coffee induce autophagy in the liver, muscle tissue, and heart. This effect persists even when the coffee is given alongside ad libitum food. These mice didn’t have to fast for the coffee to induce autophagy.
Certain nutrients can trigger autophagy, too….
Curcumin, the primary phytonutrient in turmeric, is especially effective at inducing autophagy in the mitochondria (mitophagy).
The anticancer potential of its main antioxidant, oleuropein, likely occurs via autophagy.
Disclaimer: The autophagy/nutrient literature is anything but definitive. Most studies take place in test tube settings, not living humans. Eating some turmeric probably won’t flip a switch and trigger autophagy right away, but it won’t hurt.
Autophagy is a long game.
This can’t be underscored enough: Autophagy is a lifelong pursuit attained by regular doses of exercise and not overeating every time you sit down to a meal. Staying so ketotic your pee tests look like a Prince album cover, doing epic 7-day fasts every month, fasting every other day, making sure you end every day with fully depleted liver glycogen—while these strategies might be “effective,” obsessing over their measures to hit some “optimal” level of constant autophagy isn’t the point and is likely to activate or trigger neurotic behavior.
Besides, we don’t know what “optimal autophagy” looks like. Autophagy isn’t easy to measure in live humans. You can’t order an “autophagy test” from your doc. We don’t even know if more autophagy is necessarily better. There’s the fact that unchecked autophagy can actually increase existing cancer in some cases. There’s the fact that too much autophagy in the wrong place might be bad. We just don’t know very much. Autophagy is important. It’s good to have some happening. That’s what we have to go on.
Autophagy happens largely when you just live a healthy lifestyle. Get some exercise and daily activity. Go hard every now and then. Sleep deeply. Recover well. Don’t eat carbohydrates you don’t need and haven’t earned (and I don’t just mean “earned through glycogen depleting-exercise”). Reach ketosis sometimes. Don’t eat more food than you need. Drink coffee, even decaf.
All those caveats aside, I see the utility in doing a big “autophagy session” a few times a year. Here’s how mine looks:
I know people are often skeptical of using “Grok logic,” but it’s likely that most human ancestors experienced similar “perfect storms” of deprivation-induced autophagy on occasion throughout the year. You track an animal for a couple days and come up short, or it takes that long to make the kill. You nibble on various stimulants plucked from the land along the way. You walk a ton and sprint some, then lift heavy. And finally, maybe, you get to eat.
If you find yourself aging well, you’re on the right track. If you’re not progressing from obesity to diabetes, you’re good to go. If you’re maintaining and even building your muscle despite qualifying for the blue plate special, you’ve probably dipping into the autophagy pathway. If you’re thinking clearly, I wouldn’t worry. Obviously, we can’t really see what’s happening on the inside. But if everything you can verify is going well, keep it up.
That’s it for today, folks. If you have any more questions about autophagy, leave them down below and I’ll try to get to all of them in future posts.
Thanks for reading!
Yang ZJ, Chee CE, Huang S, Sinicrope FA. The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther. 2011;10(9):1533-41.
Barlow AD, Thomas DC. Autophagy in diabetes: ?-cell dysfunction, insulin resistance, and complications. DNA Cell Biol. 2015;34(4):252-60.
Sasaki Y, Ikeda Y, Iwabayashi M, Akasaki Y, Ohishi M. The Impact of Autophagy on Cardiovascular Senescence and Diseases. Int Heart J. 2017;58(5):666-673.
Florencio-silva R, Sasso GR, Simões MJ, et al. Osteoporosis and autophagy: What is the relationship?. Rev Assoc Med Bras (1992). 2017;63(2):173-179.
Li Q, Liu Y, Sun M. Autophagy and Alzheimer’s Disease. Cell Mol Neurobiol. 2017;37(3):377-388.
Jiao J, Demontis F. Skeletal muscle autophagy and its role in sarcopenia and organismal aging. Curr Opin Pharmacol. 2017;34:1-6.
Schwalm C, Jamart C, Benoit N, et al. Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation. FASEB J. 2015;29(8):3515-26.
De oliveira MR, Jardim FR, Setzer WN, Nabavi SM, Nabavi SF. Curcumin, mitochondrial biogenesis, and mitophagy: Exploring recent data and indicating future needs. Biotechnol Adv. 2016;34(5):813-826.
Przychodzen P, Wyszkowska R, Gorzynik-debicka M, Kostrzewa T, Kuban-jankowska A, Gorska-ponikowska M. Anticancer Potential of Oleuropein, the Polyphenol of Olive Oil, With 2-Methoxyestradiol, Separately or in Combination, in Human Osteosarcoma Cells. Anticancer Res. 2019;39(3):1243-1251.