June 7, 2020

Autophagy for Longevity and Long-Term Health

What is Autophagy?

The term "autophagy" was not chosen randomly and translates to "self-eating." Autophagy is a catabolic process that breaks down components of your body's cells in order to use them in the creation of new cells. It is a recycling mechanism known as homeostasis.

The cytoplasm is a "jelly-like" substance that is located outside the cell's nucleus. When autophagy occurs, cytoplasm and tiny structures with unique functions, known as organelles, are removed from the cell and recycled. This process is vital and keeps your body in balance, as it removes cells that are no longer working properly. There are several diseases (especially neurodegenerative disorders), such as Parkinson's, which are known to disrupt the autophagy process.

How does it work?

Autophagy sets in when a cell doesn't get sufficient nutrients. There are four stages during the process of autophagy:

1. Sequestration

In this step, the phagophore (a double-membrane) moves around the cytoplasm and organelles until they are completely enclosed. Then the phagophore turns into an organelle called the autophagosome.

2. Fusion

The autophagosome cannot attach to a lysosome directly. So it starts to merge with a structure called an endosome. When an autophagosome merges with an endosome, it is referred to as an amphisome. An amphisome has the ability to merge with a lysosome.

3. Degradation

After the amphisome has fused with the lysosome, degradation starts to take place — the lysosome releases hydrolases (a type of enzyme) that degrade materials previously enclosed by the autophagosome. The structure with the now-degraded cellular material is called autophagolysosome or autolysosome.

4. Reuse

After the cellular materials have been fully degraded, converted into the amino acids, and exported away from the autophagolysosome right into the cellular fluids, these amino acids can now be reused by new cells.

The broken-down amino acids are used in the TCA cycle (commonly called citric acid cycle). This is a chain of chemical reactions that serves as a central driver for cell respiration. NAD+, one of our best-selling supplements, plays an essential role in most of the reactions within the TCA cycle.

The different types of Autophagy

There are three similar types of autophagy with distinct features:

1. Macro Autophagy

This refers to the general autophagy process, as outlined above.

2. Micro Autophagy
This process also engulfs and degrades different cell structures; however, it does not utilize a phagophore during the sequestration process. Instead, a lysosome sucks in the cellular contents and starts to engulf material around its membrane. Then the contents are broken down into amino acids, which can be recycled.

3. Chaperone-mediated Autophagy
This is a selective autophagy process, where proteins are targeted in order to be degraded. So-called chaperone-proteins assist in the translocation of degradable proteins along the lysosome membranes.

Anti-Aging and Longevity

Autophagy is a stress (stress being cell starvation) response that rejuvenates cells and causes them to become more conservative with their energy use and more resilient to damage. Research has shown that the activation of autophagy suppresses the age-associated accumulation of corrupted cellular structures and greatly improves the metabolic efficiency of targeted cells.[i]

Autophagy can also be triggered to remove malfunctioning mitochondria that produce many harmful ROS (reactive oxygen species), which contribute to cell degradation. This process is known as mitophagy.[ii]

Inducing autophagy was also proven to extend the lifespan of mice.[iii]

Other benefits of Autophagy

Autophagy not only has anti-aging benefits but may also play a key role in the prevention of age-related diseases. Autophagy removes toxic proteins that are known to contribute to the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease.

Many cells, which no longer work, can do harm by mutating and multiplying, which forms the basis for the spread of every type of cancer. Autophagy prevents malfunctioning cells from multiplying by breaking down the corrupted structures within the cell into amino acids. Thus many medical professionals believe that autophagy plays a vital role in the prevention and treatment of cancer. The body detects what's wrong, destroys it, and conducts "repair work," thus increasing genomic stability. While there is no concrete scientific evidence to back up this hypothesis, the results of one study provide further indications in support of this theory.[iv]

Here is a brief summary of all known or presumed benefits of autophagy:

Regulates cells' mitochondria, thus improving the body's energy production.
It protects the immune and the nervous system.
Prevents metabolic stress.
It is believed to protect against heart disease and cognitive decline as it promotes new cell growth, especially cells in the brain and heart.
Prevents inflammatory diseases like Krohn's, as it restores the lining of the gut, thus improving digestive function.
Protects our genes, as it stabilizes our DNA.
May prevent and treat every type of cancer, as it is believed to be a bona fide tumor suppressor.
Is known to slow down aging by rejuvenating our body with new cells without increasing energy demand.

Ways to induce autophagy

With so many mind-boggling health benefits that go well beyond anti-aging, you may ask yourself how you can trigger autophagy in your body. As mentioned, autophagy is a stress response. Thus, mild stress, that doesn't significantly damage our body can be beneficial by activating autophagy. Numerous studies have helped identify several measures you can take every day in order to induce autophagy. Most notably:

1. Nutrition

Resveratrol was reported to have an autophagy-inducing effect. [v]
Pterostillbene, another polyphenol closely related to resveratrol, albeit much more potent and bioavailable, was also found to induce autophagy. [vi] Read more about the health benefits of pterostilbene.
A mouse study, not only proved that curcumin can reverse damage from osteoarthritis, but can also activate autophagy. [vii]
Just like turmeric's curcumin, ginger's 6-Shogoal was also found to induce autophagy.[viii]
The active ingredient in cinnamon was also found to trigger autophagy.[ix]
Coffee was proven to increase autophagy in mice. [x]
…As was an active ingredient in green tea, albeit at a dose equivalent to ten cups of green tea per day. [xi]

2. Exercise

Exercise was shown to induce autophagy in peripheral muscle and brain tissue in mice.[xii]
Meanwhile another study suggests, that physical exercise may trigger autophagy in organs that partake in the metabolic regulation process. (i.e. liver, adrenal glands, thyroids, etc.) [xiii]. So besides all the other invaluable health benefits of cardiovascular exercise, it is also a great way to put your cells under "healthy" stress and expose them to autophagy.

3. Intermittent fasting and caloric restrictions

Fasting has many benefits, such as decreasing inflammation levels , boosting brain function [xiv] and increasing HGH (human growth hormone) secretion [xv]. These benefits might be possible, not directly through fasting, but as a side effect of autophagy. Another mice model proved that autophagy could also be induced through intermittent fasting and restricting ones caloric intake [xvi]. Thus, frequent, short-term fasting may be a viable method to combat neurological conditions and cancer growth [xvii].

4. Adequate Sleep

Autophagy is also triggered during sleep. The circadian rhythm, which we've covered extensively before and is itself directly related to anti-aging, controls our sleep cycle, and is directly linked to autophagy [xviii]. Another study derived at the conclusion that lack of REM (Rapid Eye Movement) sleep may negatively affect autophagy in neurons, leading to altered brain function [xix]. A mice model also demonstrated, that disrupting mice's sleep, also disrupted their autophagy protein transmission [xx].

References:

[i] https://www.ncbi.nlm.nih.gov/pubmed/25654554

[ii] https://www.ncbi.nlm.nih.gov/pubmed/24079773

[iii] https://pubmed.ncbi.nlm.nih.gov/23939249/

[iv] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388596/

[v] https://www.ncbi.nlm.nih.gov/pubmed/25068516

[vi] https://www.sciencedirect.com/science/article/pii/S1021949816301855

[vii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028754/