Luisa Torres, PhD
Luisa is a science communications manager at LifeOmic and neuroscientist and science writer covering topics related to aging, metabolism, and brain health.

Luisa Torres, PhD
Luisa is a science communications manager at LifeOmic and neuroscientist and science writer covering topics related to aging, metabolism, and brain health.


 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? 

What you’ll find in this article:

What is autophagy? | How does autophagy happen in your body? | mTOR and AMPK | The effect of age  | How long do I need to fast to increase autophagy ? | Intermittent fasting and exercise turn on autophagy | Foods that induce autophagy | Signs your cells are performing autophagy  | Effects of autophagy on cancer, neural stem cells and hematopoietic stem cells

* Illustrations by Tori Rogers.

What is it?

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. There, damaged cell parts 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, such as when you’re fasting or working out.  

When you fast or exercise, your body can remove old components 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. 

How does it occur?

When your cells are ready for the process of autophagy,  3 things occur:

  1. A cup-shaped structure known as the phagophore begins to form around damaged components cartoon representation of the phagophore, the structure that forms around the cell parts to be recycled during autophagy.
  2. The edges of the phagophore extend and fuse, forming a new structure known as the autophagosome. This is the ‚Äėrecycling bin‚Äô that will contain the damaged material.
  3. cartoon representation of the autophagosome, the structure that forms when the ends of the phagophore extend and fuse. this occurs during autophagy.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 rids your body of dangerous things that can cause disease, such as faulty proteins and even bacteria and viruses.

cartoon representation of the autophagosome fusing with a lysosome. This occurs during autophagy.

Autophagy can be ramped up and decreased as needed

mTOR (mammalian target of rapamycin) is a protein that normally¬†prevents autophagy.¬†It becomes active when you eat and nutrients are plentiful. However, when you do¬†intermittent fasting for ¬†several hours, a protein known as AMPK (5′ AMP-activated protein kinase) turns off mTOR and signals your body to go into self-protective mode. This activates several proteins, including those known as autophagy‚Äźrelated genes, which initiates the process of autophagy by helping gather damaged cell parts and fusing them to the lysosome to be broken down.¬†

Rapamycin, which is a natural mTOR inhibitor, is a potential treatment against cancer because it inhibits tumor growth.

Animal research shows 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. 

The effect of age 

The autophagy process becomes less efficient as you age. This causes your cells to accumulate damage they’re unable to repair, which may lead to Alzheimer‚Äôs, Parkinson‚Äôs 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.

How long do I need to fast for increased autophagy?

After 16 hours of fasting, neurons switch from using glucose to using ketones as their primary energy source. Ketones have been shown to promote the autophagy process in neurons. Therefore, it’s possible neurons ramp up autophagy 16 hours into a fast.

A 2019 research 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 research study, skeletal muscle biopsies of healthy male volunteers who fasted for 72 hours showed reduced mTOR and increased autophagy.

Autophagy increases throughout your fast. Be sure to fast for at least 16-18 hours per day to see the benefits of cellular recycling.

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

Intermittent fasting and exercise increase autophagy and improve health

Intermittent fasting is not the only way to enhance the ability of your cells to perform the autophagy process. Dr. Beth Levine’s research 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.
Physical activity, just like fasting, inactivates mTOR and activates AMPK.

High-intensity exercise encourages your cells to recycle

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.

Foods that turn on the recycling button

In general, your body cells need a low-nutrient environment to increase autophagy. This ideal environment is usually achieved through intermittent fasting and exercise. However, there are natural compounds found in fruits, vegetables and spices that make your cells go through the process of autophagy without the need to actually to intermittent fasting.

They include the following:

Berries

Berries and grapes contain stilbenes which can activate the Nrf2 signaling pathway associated with antioxidant defense and elimination of damaged cell components. Stilbenes can also prevent cancer and prevent the progression of malignant tumors.

Red wine

Resveratrol in grapes and red wine turns on autophagy by activating AMPK and turning off mTOR.

Resveratrol also keeps breast cancer cells from proliferating and increases sensitivity to cancer treatment with cisplatin.

Curcumin (turmeric)

This compound is a strong anti-inflammatory that can manage arthritis symptoms. It also helps your cells get rid of damaged mitochondria and can enhance the activity of lysosomes, the recycling plant of the cell where damaged components are broken down and reused during autophagy.

Curcumin also increases sensitivity to cancer treatment gefitinib and induces cell death in gastric cancer cell lines.

Broccoli and Brussels sprouts

Cruciferous vegetables are a source of sulforaphanes. These compounds turn on the NRF2 pathway which is anti-inflammatory and prepares your cells to deal with oxidative stress.

Green leafy vegetables

Green leafy vegetables and beetroots contain nitrate (NO3‚Äď), which your mouth bacteria convert into nitrite (NO2‚Äď). ¬†In your stomach, nitrite forms nitric oxide (NO), which can dilate blood vessels and¬†activate autophagy through activation of AMPK.

Coffee

Polyphenols found in coffee, tea, red wine and cocoa may enhance the conversion of nitrite into NO in the stomach, which favors autophagy by turning on AMPK.

Coffee has been shown in cell culture and animal model studies to enhance autophagy in liver, muscle and even brain cells.

A study showed that caffeine promotes autophagy in the skeletal muscle of rats.

Another study found that both natural and decaffeinated coffee increased autophagy in mice 1-4 hours after coffee consumption. There was higher autophagy in the liver, heart and muscles.

Signs your cells are in cleaning mode

Unfortunately, you can’t measure autophagy the way you can measure blood glucose or ketones. However, research shows that ketones induce autophagy. Therefore, if your ketone meter¬†indicates you are in ketosis, it’s likely that your body is getting rid of damaged cell parts at increased levels.

You can easily measure ketone levels in blood or breath throughout your fast.

The effect of cellular recycling on cancer

The autophagy process is an essential protective mechanism against inflammation, oxidative stress and DNA damage, which ultimately protects from cancer. However, cancer cells are known to use autophagy to promote their own survival by generating nutrients and blocking cancer treatment.

If cancer is already occurring, the effect of autophagy seems to depend on how advanced the cancer is. In the early phases, autophagy can induce an anti-cancer immune response. During advanced cancer stages, autophagy can promote cancer by providing nutrients to the tumor, promoting invasion and creating resistance to radiation and chemotherapy.

This double-edge sword effect makes it difficult to implement in cancer treatment. It could be used as a preventive approach in patients at high risk of cancer, instead of inducing it directly when cancer has fully developed.

The effect of cellular recycling on neural stem cells

Neural stem cells are the stem cells of the brain and spinal cord. During development they give rise to the entire nervous system. In the adult brain a small number of mostly dormant cells remain.

Neural stem cells can either self-renew to maintain their pool, or they can activate and become a specialized brain cell. This makes them critical for repairing brain tissues. The ability of neural stem cells to activate declines with age, which means new nerve cell formation in the adult brain is reduced.

Autophagy is critical for neural stem cell survival and  function. Research shows that autophagy helps neural stem cells self-renew to maintain their reservoir. It also helps clear age-induced protein aggregates, induces their activation and provides neural stem cells with the energy needed to become specialized brain cells. In the context of brain or spinal cord injury,  autophagy can reduce inflammation and promote their differentiation so they can participate in tissue repair.

Neural stem cells can either self-renew to maintain their pool, or they can activate and become a specialized brain cell. Cellular recycling is critical for neural stem cell survival and  function.

The effect of cellular recycling on hematopoietic stem cells

Adult hematopoietic stem cells live in the bone marrow and they can give rise to all blood cells in a process known as hematopoiesis. Hematopoiesis ensures we have a life-long supply of blood cells. This helps prevent blood disorders such as anemia.

Research shows that autophagy helps maintain the pool of hematopoietic stem cells by protecting them from cell death. When new blood cells are needed, autophagy helps hematopoietic stem cells become specialized blood cells by preventing oxidative stress and DNA damage. Defective autophagy in hematopoietic stem cells can lead to blood disorders, including anemia.

Hematopoietic stem cells can also induce autophagy as a self-protective mechanism when they’re under stress.

The bottom line

Autophagy can renovate your cellular components, protect you from cancer and brain disorders, 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 move your body daily! 

Learn more about autophagy with our illustrated flashcard mini course!


Luisa Torres, PhD

I'm a science communications manager at LifeOmic and the editor of this blog. I am a neuroscientist and science writer interested in covering topics related to aging, metabolism, and brain health. I have written for NPR's blogs 'Shots', 'Goats and Soda', and 'The Salt'.

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