* Illustrations by Tori Rogers.

If you have been practicing intermittent fasting for a while, you might have heard that autophagy is one of its many benefits. But what is it and why is it important for your health? This blog post explores the concept of autophagy, how it happens in your cells, and why intermittent fasting is about much more than just weight loss. 

Autophagy is a vital process our cells do for keeping themselves working properly. It involves packaging damaged cell components and transporting them to a recycling plant within the cell called the lysosome, where they are broken down and reused.

Your cells maintain low levels of autophagy all the time, but they ramp it up when nutrients are low, or when there is increased demand for energy, a.k.a when you’re fasting or working out.  

When you fast or exercise, your body can remove old components if they have accumulated too much damage, or turn them into things your cells can use. This gives you sugars and other building blocks that can power you through a fast or a workout. 

When your cells are ready for autophagy  3 things occur:

  1. A cup-shaped structure (known as the phagophore) begins to form around damaged components 
  2. The edges of the phagophore extend and fuse, forming a new structure known as the ‘autophagosome.’ This is the ‘recycling bin’ that will contain the damaged material.
  3. The autophagosome fuses directly with a lysosome, (the cell’s recycling plant) which contains enzymes known as acid hydrolases that can digest old and damaged cell parts.
    This process
    generates sugars, amino acids, and fatty acids that cells can repurpose, and it gets rid of dangerous things that can cause disease, such as faulty proteins and even bacteria and viruses.

Autophagy can be ramped up and decreased as needed

mTOR (mammalian target of rapamycin) is a protein that normally keeps autophagy levels down. It becomes active when you eat and there are plenty of nutrients around for your cells to use. When this is the case, your cells don’t bother with autophagy because there is no need to recycle anything when nutrients are plentiful. However, when you  go without eating for several hours, a protein known as AMPK ( 5′ AMP-activated protein kinase) turns off mTOR  and signals your cells to go into self-protective mode. This activates several proteins, including those known as autophagy‐related genes, which initiate autophagy by helping gather damaged cell parts and fusing them to the lysosome to be broken down. 

Autophagy decreases with age 

Although your cells use autophagy to clean themselves up, autophagy becomes less efficient as you age. This causes your cells to accumulate damage that they are increasingly unable to repair, which is linked to many diseases of aging, including Alzheimer’s, Parkinson’s disease, and cancer.

Reduced autophagy causes premature aging and shortens the lifespan of many animals, from worms to mice to humans. Since mTOR puts the brakes on autophagy and its levels go up during aging, scientists think that increased mTOR might be the link between aging and reduced autophagy. AMPK  also decreases during aging. Decreased AMPK might act in concert with mTOR to suppress autophagy in aged cells.

There are at least 2 things you can do to increase autophagy in your cells: High-intensity exercise and intermittent fasting.

Intermittent fasting and exercise increase autophagy

There are limited studies on autophagy in humans, but animal studies show that autophagy might reverse the effect of aging on health!  For example,  restricting calories in fruit flies increases their lifespan and restricting calories in rodents consistently improves their health. These effects seem to be due at least in part to putting the breaks on mTOR and activating autophagy. 

Intermittent fasting is one way in which you can increase autophagy in your cells and possibly reduce the effects of aging. A 2019 study with 11 overweight adults who only ate between 8 am and 2 pm showed increased markers of autophagy in their blood after fasting for around 18 hours, compared to control participants who only fasted for 12 hours. A second study detected autophagy  in human neutrophils starting at 24 hours of fasting.  In a third study, skeletal muscle biopsies of healthy male volunteers who fasted for 72 hours showed reduced mTOR and increased autophagy.

But intermittent fasting is not the only way to enhance the ability of your cells to recycle old components. American scientist Beth Levine showed that some of the known benefits of exercise for overall health have to do with increased autophagy. For example, autophagy induced by exercise delays the progression of heart disease by giving the heart better quality cell parts and reducing oxidative damage.

A cartoon representation on the effects of exercise on the autophagy. An exercise character high-fives an AMPK character with a 'recycling'facility in the background.
Exercise, just like fasting, inactivates mTOR and activates AMPK.

Exercise, just like fasting, inactivates mTOR, which increases autophagy in many tissues. Exercise mimics the effects of going without food for an extended period: It activates AMPK as well as autophagy-related genes and proteins. 

In mice, endurance exercise increases autophagy in the heart, liver, pancreas, fat tissue, and brain. In humans, autophagy increases during high intensity exercise, including marathon running and cycling.

Autophagy can renovate your cellular components, protect your brain by removing damaged proteins, keep diseases away by getting rid of foreign bacteria and viruses, provide your cells with energy when food is scarce, and protect you from DNA damage. Practice intermittent fasting  and exercise daily– You might end up living healthier and longer because of it. 

Learn more about autophagy with our illustrated flashcard mini course!