What Is Autophagy and How Can It Promote Longevity?

Detoxification is a well-known mechanism through which the body gets rid of harmful organisms and toxins, allowing cells, organs, and the immune system to function optimally. It’s not the only way the body “heals” itself, though. There’s a process that has been found to play a critical role in disposing of damaged cells and recycling their components into new ones to maintain homeostasis.

Key takeaways:
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    Autophagy is the process by which the body removes damaged cells.
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    Autophagy plays a key role in fighting inflammation and aging-related diseases.
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    Timed eating and exercise may help promote autophagy.

It, however, slows down with aging, and your lifestyle choices may also inhibit and downregulate its activation. It’s called autophagy.

What is autophagy?

In translation from its Greek origin, the word “autophagy” means “self-eating,” as the body performs a self-degradative process removing the parts of misfolded proteins, damaged cells, and pathogens and recycling their cellular components to create new and healthy cells.

Don Moxley, exercise physiologist and director of applied sciences at Longevity Labs, told Healthnews that it is “an internal cellular cleaning process that’s evolutionarily present in all animals, which is why much of the research that’s been done looked at this process in fruit flies and mice, before humans.”

Belgian scientist Christian de Duve was the first to coin the term in 1962 as part of his research discovering lysosomes (the digestive organelles of the cell), for which he shared a Nobel Prize with two other scientists in 1974.

Autophagy, however, wasn’t mainstream until nearly 40 years later, when Japanese cell biologist Yoshinori Ohsumi won the Nobel Prize in Physiology or Medicine for his discovery of mechanisms for autophagy in 2016.

Since then, practices such as fasting, heat or sauna therapy, and various supplements have become popular to upregulate autophagy, and hence, achieve better health and longevity.

Studies have also shown how autophagy may have the ability to help against various diseases such as Alzheimer’s Disease, Type 2 Diabetes, cardiovascular disease, and more. Nonetheless, science only uncovered the tip of the iceberg when it comes to fully understand autophagy.

How does autophagy work?

Moxley said autophagy is always present inside the cell, so instead of it being an “on-and-off” switch, certain actions may either upregulate or downregulate it (we’ll talk about why it matters in the next section).

One of the main ways autophagy is induced is by depriving the cell of nutrients or oxygen that would provide them with energy. With the lack of external resources, the body turns inward for creating energy and begins to break down old and damaged cells into their parts and reuse their components to create new ones.

In his book, “Lifespan,” David Sinclair describes autophagy as a process through which cells divide less, and instead, hunker down and “reuse old cellular components to maintain energy and extend survival.”

It was found to be a key pathway during the ancient times of feast and famine when our ancestors would go extended periods without food. Autophagy allowed the body to maintain homeostasis.

Additionally, research has found that autophagy helps avoid the build-up of dead and senescent “zombie” cells that fuel inflammation and decrease overall cell function. Therefore, it may serve as a therapeutic intervention for diseases associated with inflammation.

Why is autophagy important for longevity and overall well-being?

It is now more commonly understood that health and healthy aging begin at the cellular level. When your cells and mitochondria function optimally, your organs work better, and hence, your entire bodily system is more optimized.

However, your daily actions in terms of nutrition, exercise, sleep, and other lifestyle choices can either promote healthy cell function and lower inflammation or increase inflammation and create cell dysfunction and protein misfolding. By initiating the body’s survival mechanism and upregulating autophagy, you can help your body to correct those errors, and, perhaps, even slow down aging.

The anti-aging aspect of autophagy is seen in its association with the activation of the anti-aging gene (Sirtuin 1), the decrease of reactive oxygen species and inflammation, cell repair, and its boost of brain-protective chemicals.

Moxley said the reason why autophagy is proving to be therapeutic with many health conditions is due to its role in lowering inflammation which, when chronic, was found to be the root of many of our preventable modern lifestyle diseases.

“When autophagy goes up, inflammation goes down and vice versa,” he said, adding, “There’ve been 67 different proteins in a cell that’s been found to relate to autophagy either as a trigger or facilitator. The more upregulated autophagy is, the more you deal with decreasing inflammation.” He adds, “inflammaging” is what we face when inflammation expedites the aging process.

Additionally, a study published in Nature provided evidence for the cognitive benefits of autophagy. It reported that autophagy played an important role in increasing brain-derived neurotrophic factor (BDNF) signaling that protects cognitive function and boosts neuroplasticity, the brain’s ability to change and create new neural pathways.

What inhibits autophagy?

Some of the main aspects that inhibit autophagy are:

  • Eating too much.
  • Eating too often.
  • Sedentary lifestyle.

Ways to upregulate autophagy

Fasting and caloric restriction

Fasting and time-restricted eating in a cycling fashion activate the Sirtuin 1 gene (Sirt1) that promotes autophagy. Depriving the body of nutrients, particularly, protein and carbohydrates (glucose), results in the interruption of mTOR (mammalian target of rapamycin) signaling, which has been found to stimulate autophagy.

Cycling is, however, a key component. While you want the body to upregulate its “housekeeping” mechanism, it’s also important to then “re-feed” with high-quality nutrients (fat, protein, and fiber) to reactivate the mTOR signaling to use those nutrients to build new cells. As a result, your body can cleanse during a fast and rebuild when eating. Moxley recommends practicing a 6-hour feeding/18-hour fasting or 8-hour feeding/16-hour fasting window as a safe place to start.


Pharmaceuticals such as metformin and rapamycin are two prescription drugs that play a role in that pathway by suppressing mTOR activity, and hence, promoting autophagy.

Another molecule that’s been found to support autophagy is spermidine. According to a recent study, dietary supplementation with this natural polyamine extended life span and reversed aging-associated cardiac dysfunction in mice through induction of autophagy.


“Don’t exercise to lose weight,” Moxley said. “Exercise to boost autophagy to lower inflammation, to build mitochondrial integrity, and upregulate AMPK.” Weight loss and healthier body composition will be a byproduct.

Ketosis through a high-fat, low-carb diet

Research has shown a positive correlation between ketogenic interventions and autophagy activation along with improved vascular health. You can achieve ketosis while fasting, or by eating a high-fat, low-carb, and moderate-protein diet.

Heat therapy

A study published in the Journal of Applied Physiology pointed out that observations in animal and cell culture models regarding the effect of using heat therapy to restore autophagy appear promising. Yet more research is needed on whether heat therapy, such as sauna, induces autophagy in humans.


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