Autophagy and healthy cell maintenance

What is autophagy?

Autophagy is an important process for maintaining healthy cells. It is a kind of natural anti-aging mechanism, which cleans up old cells to better protect well-functioning cells (1, 2). This is done by means of autofagosomes. These autophagosomes selectively capture old cells and convert them into energy, which is then used for metabolic and biosynthetic processes (3).

It took a long time for the role of autophagy in the human body to be understood. In the 1960s, the process was named autophagy, which literally translates to “self eating” (4). It wasn’t until the 1990s, when Yoshinori Ohsumi researched autophagy in yeast cells, that it became clear that there are certain genes that drive autophagy (5). This research has led to numerous investigations into autophagy. For example, in 2010, newborn mice were shown to die within 24 hours, after the autophagy-related gene ATG5 was removed from their bodies (6). In 2016, Yoshinori Ohsumi was awarded the Nobel Prize in Physiology or Medicine, for all the research he has done on autophagy (7).

We now know that autophagy is a process that helps protect our cells under all kinds of stressors. Such stressors are caused by refraining from eating over a longer period of time, viral infections or intense exercise (8). If the autophagy process is out of balance due to continuous suppression, the body ages faster. As a result, one may have an increased chance of developing numerous chronic diseases (9).

For whom is it interesting to stimulate autophagy?

As one gets older, autophagy in the body decreases (10). This makes it more likely that older people have a lack of autophagy than young people. This makes stimulating autophagy more interesting for adults, than people who haven’t reached adulthood. 

But why does autophagy decrease as one gets older? Autophagy is suppressed by a modern lifestyle, to which our species has not yet genetically adapted. In this modern lifestyle, we learn to have breakfast and to eat multiple meals throughout the day. Besides grazing throughout the day, the modern diet consists mainly of carbohydrates. The idea that a cereal breakfast would be healthy is the result of a good marketing stunt. All kinds of factors that are part of this modern lifestyle contribute to a decrease in autophagy. The decline of autophagy seems to be a cause of aging rather than the consequence. This makes autophagy an interesting process to stimulate as a preventive medicine, but is also reason enough to further investigate the role of autophagy in treating diseases related to aging. to be investigated (2).

koolhydraten suikers autofagie mtor
Starting the day with a breakfast rich in carbohydrates, containing lots of sugars, suppresses autophagy.

A challenge in today’s health care system is that a lot of emphasis is placed on treating symptoms, but not on prevention. Causes of aging of the body are often ignored (11). Such factors that can affect the aging process are; damaged mitochondria, shortened telomeres or oxidative stress in the form of free radicals. Lifestyle adjustments through stimulation of autophagy can be a useful addition to current treatment methods.

mTOR as regulator of cell growth and autophagy

Autophagy is largely controlled by mTOR, a protein kinase that regulates cell growth (12). A protein kinase is an enzyme that can add phosphate groups to proteins, which allows it to change the structure of proteins. Stimulating mTOR leads to cellular growth, while suppression of mTOR leads to cellular protection (autophagy).

Because mTOR stimulates cell growth, stimulation of this is very important for muscle growth, to name an example (13). However, an imbalance (or excess) in mTOR can stimulate cancer development (14), diabetes (15), Alzheimer’s disease (16) or body aging (17). Therefore, it is important to find a good balance between mTOR (cell growth) and autophagy (cell protection). Please find figure 1 for an overview of factors affecting mTOR suppression and activation.

autofagie autophagy mtor balans
Figure 1. Display of factors affecting mTOR and autophagy

How can we stimulate autophagy?

Autophagy is mainly stimulated by suppression of mTOR. Because mTOR is stimulated with nutrition, mTOR can also be suppressed by fasting (18). In addition, a diet low in carbohydrates or a ketogenic diet can also suppress mTOR (19). This suppression of mTOR through fasting or a ketogenic diet is caused by a reduction in insulin or IGF-1 (20, 21)

There are also numerous dietary supplements that stimulate autophagy. For example, resveratrol,quercetin, pterostilbeen and curcumin stimulate autophagy through SIRT1 activation (22). In addition, resveratrol and pterostilbene are able to stimulate autophagy by opregulation of AMPK (23, 24). For an overview of this action path, see Figure 2.

effect resveratrol pterostilbeen mitochondriën
Figure 2. AMPK stimulates synthesis of NAD+, which is used by SIRT1 to protect body cells

In addition to dietary supplements, there are also medications that stimulate autophagy. For example, Rapamycin (prescribed under the name Sirolimus) stimulates autophagy through suppression of mTOR (25). Metformin, a drug often prescribed to diabetics, stimulates autophagy by AMPK activation (26).

Autophagy-oriented medication and treatment methods

Research in mice found that stimulation of autophagy through curcumin enhance the effect of chemotherapy (27). However, in some cases tumors become resistant to autophagy, in which case autophagy can actually protect cancer cells (28, 29, 8).

It seems that autophagy has a preventive effect on various kinds of cancers. However, depending on the type and stage of cancer, a tumor may be resistant to treatment (30).

Conclusion

Finding a good balance between mTOR and autophagy can help with a healthy cell balance, which can contribute to a well-functioning body. Due to a decrease in autophagy with age, adults in particular may benefit from consciously stimulating autophagy. The trick here is to find a balance between mTOR (cell growth) and autophagy (cell protection). A number of ways to stimulate autophagy are:

1. Shorten the time frame in which one eats, for example by fasting.

2. Consume fewer carbohydrates, for example through a ketogenic diet.

3. Supplementation by dietary supplements or medicines that suppress mTOR

4. Supplementation by dietary supplements or medicines activating SIRT1 and/ or AMPK

In our blog we mention even more tips that can contribute to a healthy lifestyle. These tips can help people stay healthy, but of course offer no guarantee.

Elixir Life and autophagy

Elixir Life’s formulas are designed to stimulate autophagy, aimed towards keeping our bodies cells healthy as we age. Because we do our own research, we can offer more effective formulas than our competitors, at a fair price.

When designing our products, we take in consideration all the flaws of standard products. We only use quality ingredients of the highest possible standardization rate for our products. The ingredients used in our formulas are all flawlessly in sync. Allowing you to stack them for a stronger, more diverse effect.

ResveraShield is an excellent resveratrol supplement to support overall health. Bright Mind is our high-quality curcumin product with a twist, intended to keep the brain cells healthy. Strong Heart is our showpiece, specially developed to boost the cardiovascular system.

Literature
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