“Four Ways to Instantly Boost Autophagy” is the title of one of dozens of videos on the World Wide Web in which commercial health authorities with dubious scientific credentials explain—or think they explain—how complex cellular machinery works.

The term became more widespread after The 2016 Nobel Prize in Physiology or Medicine was awarded to Japanese researcher Yoshinori Ohsumi. for his “discoveries about the mechanisms of autophagy”since it was considered by many to be something of a golden grail of youth preservation and longevity, it was associated with diets and diets that included fasting.

The constituent parts of this word of Greek origin describe the mechanism by which cells consume their unnecessary or harmful elements, thereby contributing to the maintenance of good health of the body. The term first appeared in the mid-19th century, but as a molecular mechanism it was defined and refined around 1950 by the Belgian cell biologist and Nobel laureate Christian René de Duve.

“At some point there will be a second Nobel laureate in autophagy,” says O. Nicholas Christakis, Principal Research Fellow, Babraham Institute, University of Cambridge, UK. As the interest of many laboratories around the world turns to the mechanism of autophagy, a promising path to understanding complex cellular mechanisms has already been opened. While the findings are still the result of fungal research, the mechanism is similar in mammalian cells, Mr. Ktistakis explains. “What was not covered by the first Nobel Prize is how autophagy is related to human physiology, to diseases and so on. – things that we can’t say yet, we know for sure that they are true.

Nicholas Ktistakis has been studying the cellular machinery of autophagy for over two decades. Last years focuses on research in the treatment of neurodegenerative and mitochondrial diseases. “I’m interested in how autophagy can help cells clear bad mitochondria and keep the good ones, so to speak,” he says.

The Importance of Fasting

From best-selling diet books to scientific treatises, the fasting process is presented as the key to activating the mechanism. “There is a basis of truth in this,” the researcher explains. “This autophagy pathway, theoretically it could help cleanse the cells, for example, from proteins that are no longer active, from organelles such as mitochondria that do not work properly. If the body has 90% good mitochondria and 10% bad, then those 10% can cause tremendous damage and lead to cell death,” he says.

The toxic substances produced in these cases to fight the cell activate another mechanism, described as “self-death”, i.e. cell self-destruction. In laboratory tests, model organisms such as Drosophila insects or c. elegans that switched to starvation immediately activated the autophagy mechanism. “Therefore, there is definitely a connection between nutrients and autophagy,” emphasizes Mr. Ktistakis.
According to the researcher, mechanism can be activated in three ways: “One n starvation. But this is not about reducing calories, but about the fact that for some time there should be no food at all. For the human body, this can be about 18 hours,” he notes. “The second one is physical exerciseat least for some websites, and the third and most controversial one is with drug control“.

The interest of pharmaceutical companies is based on the latter option, for which there are already findings, such as the substance rapamaycin, which deactivates the kinase in cells and thereby leads to autophagy. “The problem is that this kinase controls not only autophagy, but also 50 different things in the cell that are related to how it perceives the outside world. Therefore, if we start to influence the function of this protein, we will affect not only autophagy, but also many other processes in the cell, ”he adds. Hence, artificial, at least, activation of the mechanism does not bring only positive resultsbut it can also lead to negative consequences for the body.

it’s not a panacea

“For autophagy, it has been experimentally proven that there are two aspects, and we must always weigh the benefit to the patient.”

Autophagy is not always desirable, especially in cases of cancer and especially in the presence of solid tumors. “Some cells that are in the middle of the tumor. to survive, they must use autophagy. So if we made these cells even better at autophagy, that would be a negative factor for tumor progression.”

In the case of older people with neurodegenerative diseases – for which autophagy may have a positive effect, “and there is a lot of research interest at the moment” – the price could be exacerbation of some other disease that already exists. “For autophagy, it has been experimentally proven that there are two aspects, and we always have to weigh the benefit to the patient,” he adds.

Accordingly and fasting by itself is not always a safe solution. A person who consumes food of poor quality and in excessive quantities, even if they abstain from it for several hours, which could activate the mechanism, will not see any health benefits even if the autophagy mechanism were activated. On the contrary, “proper nutrition, even if it does not activate autophagy, helps to avoid diabetes, stomach problems and more,” notes Mr. Ktistakis.

It is clear that not everyone should and cannot fast. After all, it is not only the mechanism achieved by food deprivation that guarantees good cell health: “There are several other mechanisms that help cell health besides autophagy,” the researcher adds. “An extremely important mechanism is related to the quality of DNA, that is, it corrects errors that occur during DNA replication. In addition, there are other mechanisms that either fix or destroy proteins that are “broken” and not working properly.”

Does autophagy increase lifespan?

Longevity is a concern for much of the autophagy research community, but a direct link between the two has yet to be proven. “There is a gap between whether autophagy helps and whether it can do it on its own,” says Nicholas Ktistakis. “And one of the reasons we don’t know this is because we have no way to increase autophagy without affecting other systems within the cell. As we said at the beginning, this “path” is difficult. It is located in the main mechanism of the cell. It “talks” to many other “paths” within the cell, and so far we cannot influence only this one without affecting the rest of the cell’s mechanisms.”

“There is definitely a link between eating less and living longer.”

Technology in the last century has played a decisive role in increasing the amount of food available without time limits. The culture of food, shaped by modern methods of preserving and serving food, product marketing, and improved living standards in most countries of the world, has contributed to the emergence of a number of diseases with severe obesity. “There is definitely a link between eating less and living longer,” says Nicholas Ktistakis.

Fasting for 16 to 18 hours is not the only way to maintain good health, as sensible food intake alone can help prevent diseases that plague humanity in the 21st century. The mechanism of autophagy is amenable to further research with potential catalytic discoveries for human life and its quality. “It definitely has a good future. We can find useful things about autophagy. But let it not be used arbitrarily. We haven’t found everything yet.“, concludes the researcher.