Autophagy: Cellular Cleansing and the Secret to Longevity

When your home gets dirty, you clean it. If you’re feeling ambitious, you might even replace some of the old fixtures. That’s what autophagy, or the body’s consumption of its own tissue as a metabolic recycling process, does for your other, more permanent home: your body. 

When you activate or trigger autophagy, you activate cellular cleanup. You take old and damaged cell parts, and replace them with new ones. In a sense, autophagy helps regenerate your body. 

Keep reading to learn how autophagy works, the health benefits of autophagy, and how to activate this cellular recycling process. And yes, you’ll also discover the interesting truth about keto and autophagy. 

What Is Autophagy?

Autophagy is a term derived from Ancient Greek. Auto means self, phagy means eating. Self eating. The translation fits well. When you activate autophagy, your cells literally start eating themselves—recycling old parts and replacing them with new ones.

Why clean and recycle cell parts? Because over time, they accumulate damage. This damage is driven, in part, by molecules called reactive oxygen species (ROS).

ROS aren’t all bad. They’re generated as part of normal metabolism, and they are valuable immune-signaling molecules to boot. 

But as we age, ROS can wear down and damage your cellular machinery. The term “oxidative stress,” in fact, refers to the wear-and-tear these molecules have on your cells. 

Oxidative stress is serious business and can literally destroy the membranes surrounding your cells. Oxidative stress also corrodes your mitochondria (tiny organelles powering your cells) over the years, leading to a functional decline or even cell death. 

Your mitochondria could use a refresh, and that’s where autophagy comes in. Autophagy may, in fact, improve mitochondrial function, especially in neurodegenerative disorders like Alzheimer’s and Parkinson’s.

Next up—for all you science lovers—a bit of explanation on how autophagy actually works. 

How Autophagy Works

Autophagy doesn’t happen randomly. Your cells must receive a cleanup signal from your body.  

This signal is largely controlled by two nutrient-sensing pathways:

  1. AMP-activated protein kinase (AMPK) — this activates autophagy
  2. mammalian target of rapamycin (mTor) — this inhibits autophagy

AMPK is your internal warning alert that your body needs nutrients. Triggered intentionally by a fast or starvation, AMPK signals your body to hunker down and activate cellular defense mechanisms. One of these mechanisms is autophagy.

MTor, on the other hand, is a growth pathway, and inhibits autophagy. Eating a steak boosts mTor, while fasting suppresses it.

Simply put: to encourage autophagy, you want to activate AMPK and suppress mTor.

Once autophagy gets sparked, your cells go into an autophagic state and start eating themselves. Cleanup time! 

Here’s how this works:

    • The autophagosome (a double-membraned vesicle containing cellular material slated to be degraded by autophagy) hauls cellular junk to the lysosome (an organelle containing degradative enzymes in a membrane)
    •  The lysosome unleashes enzymes to break the cellular junk into usable materials, like amino acids
    • Your cell uses these amino acids to form new cell parts

The fact is, autophagy is best described as recycling, not cleaning. The old materials aren’t wasted, but instead reallocated for new construction projects. Pretty cool. 

Why Induce Autophagy?

What is the role of autophagy? Why induce it? Well for one: when autophagy isn’t induced, bad things appear to happen in the human body. Impaired autophagy, in fact, is linked to a long list of diseases and conditions: Parkinson’s, Alzheimer’s disease, Huntington’s, AL amyloidosis, neurodegeneration, cardiovascular disease, and cancer—to name a few.

And yet much of the data on the benefits of autophagy come from animal studies; worms, flies, and mice sacrificed in controlled settings to measure autophagy levels.

It’s not easy to measure autophagy in humans. The average person isn’t keen on muscle biopsies. So keep in mind, when reading the next section, that human data on autophagy benefits isn’t exactly grade A. 

Keto-Mojo Benefits of Autophagy

The Benefits of Autophagy

Here’s a list of potential autophagy benefits, along with brief descriptions of the research:

  • Longevity: In numerous animal studies, researchers have shown that increasing autophagy (via fasting, genetic engineering, or supplementation) increases lifespan. Does it apply to humans? Unclear.
  • Improves metabolism: Autophagy helps protect pancreatic beta cells—which may offset the insulin resistance in type 2 diabetes.
  • Brain protection: Fasting activates neuronal autophagy that helps clear proteins (like amyloid beta) linked to neurodegenerative disease. (Alzheimer’s, dementia, etc.)
  • Cancer suppression: Autophagy helps remove damaged proteins involved in tumor formation. However, once the tumor is formed, autophagy may enhance cancer cell survival.
  • Cardiovascular health: Research suggests that activating autophagy in cardiac tissue may reduce the risk of heart disease. Stay tuned on this one.
  • DNA repair: DNA damage underlies many diseases. Based on animal and test-tube evidence, scientists speculate that autophagy may promote DNA repair and reduce chronic disease risk.

How to Activate Autophagy

Recall that high AMPK and low mTor signal autophagy. The most reliable way to make this happen? Fasting.

Long fasts probably induce more autophagy than short-term caloric restriction and nutrient deprivation, but there isn’t enough data to recommend an optimal autophagy protocol yet. 

There are a variety of fasts that are popular at the moment for weight loss, improved immune-system response, and more. Some are liquid fasts that can go on for a set number of days. There is also intermittent fasting, which involves eating a specific amount of macros within a fixed window on a daily or semi-daily basis; a popular version—”16/8”—involves eating in an 8 hour window (say, from 11 AM to 7 PM) and then conducting a 16-hour fast for the rest of the day. 

Other autophagy-activators include:

Finally, the topic you’ve been waiting for. Does a higher fat low-carb ketogenic diet induce autophagy?

Keto and Autophagy

Recent evidence suggests that yes, a keto diet (where your body relies on ketones for energy instead of carbs) does activate autophagy; in animals, at least. In a 2018 study, researchers showed that putting rats on a keto diet boosted autophagy and protected their brains from seizure-induced damage.

Again, AMPK is the likely driving force in the keto-autophagy effect. Keto boosts AMPK, and AMPK signals autophagy. There’s a reason, after all, that keto is called a fasting mimicking diet. Both fasting and keto change your metabolism in similar ways.

The Final Word

To summarize what you just learned about autophagy:

  • Autophagy happens at a cellular level and is when your cells digest and recycle damaged cellular components.
  • AMPK and mTor – your nutrient-sensing pathways – govern your level of autophagy.
  • Autophagy isn’t just about cleaning, but also about reusing raw materials.
  • Though human data is lacking, autophagy may promote healthy aging, heart health, DNA repair, brain health, and a healthy metabolism. 
  • Fasting is the most reliable way to activate autophagy and autophagy-related health benefits.
  • Early animal data suggests a keto diet can induce autophagy.

While the world waits for better data, don’t stress about activating autophagy. Fast occasionally, enjoy a cup of coffee, and consider trying a keto diet. Then kick back, relax, and picture your cells renewing themselves. 





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