Autophagy: fasting for a short time, living longer and healthier
A balanced diet based on the concept of intermittent fasting ensures a longer, more active life. Responsible for this is a process called autophagy, which is something like the body’s own recycling mechanism. Here you will learn how autophagy works and what you can actively do yourself with simple means to achieve holistic health and prevent numerous diseases such as Alzheimer’s, diabetes and cardiovascular problems.
What is autophagy?
Autophagy or autophagocytosis is the process of the body’s own purification. This is the digestion of superfluous and harmful deposits, which takes place thousands of times a day in every single body cell. If this mechanism is out of balance, numerous diseases such as cancer, chronic bowel disease and Alzheimer’s disease will develop.
The term autophagy comes from the ancient Greek and is composed of the two words auto=self and phagein=eat. It was used for the first time by the Belgian scientist Christian de Duve, who had already devoted himself in the 1950s to intensive research into the body’s own detoxification mechanisms. In 1974 Duve was awarded the Nobel Prize for his groundbreaking research. Nevertheless, the details of this process could not be deciphered for decades. The breakthrough finally came from cell biologist Yashinori Ohsumi from the University of Tokyo, who had been trying to find the genes involved in autophagy since the 1990s. He identified 15 involved hereditary factors, for which he was awarded the Nobel Prize for Medicine in 2016.
- Autophagy – endogenous recycling
- Cellular building blocks for autophagy
- The different processes of autophagy
- Autophagy under the magnifying glass: The steps of cellular self-digestion
- Autophagy is controlled by the genes
- Self-digestion and suicide of the cells are close together
- Self-healing through a functioning autophagy
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Autophagy – endogenous recycling
Cellular building blocks for autophagy
The strong cells are the basic building blocks of the organism. They are constantly busy developing, renewing and multiplying themselves. In order to understand how autophagy works in detail, it is important to first understand the structure and functioning of these small powerhouses.
Lysosomes – decomposition of old and construction of new macromolecules
Not only in the household, but also on every level of the body, garbage must be disposed of regularly. Cells are limited to the outside by a plasma membrane. In its interior is the so-called cytoplasm. This cytoplasm is aqueous in consistency and forms the carrier substance for the cell nucleus and various organelles such as lysosomes, mitochondria and ribosomes. The lysosomes are also enclosed by a membrane and contain various enzymes called acid hydrolases. These are responsible for breaking down fats, sugars, proteins and nucleic acids within the cell. By breaking down these complex molecules and releasing them again, new macromolecules can be built. Therefore, the lysosomes are often called the “recycling plant of the cell”.
Ribosomes take over the protein synthesis
Ribsomes are composed of a complex compound of proteins and ribonucleic acid. Protein synthesis takes place in the ribosomes. In this process, individual amino acids are converted into long-chain polypeptides.
A ribosome represents a self-sufficient production site for each protein to be synthesized in the body.
Mitochondria – power plants of the cells
The strong mitochondria are among the best known strong cellular building blocks. They are often called “power plants of the cells” and are responsible for the energy supply of the organism.
In order to maintain body substance, the cells must maintain an active metabolism . Metabolism refers to both build-up, supply and breakdown of proteins, carbohydrates, fats and nucleic acids. The mitochondria provide the necessary energy for this. Since this resource is still not available indefinitely, the cells must be correspondingly economical with this resource.
In the course of the Strong Evolution, they have developed a technique to split up all unused organelles or proteins completely into their individual parts.
This is a self-digestion process in which the decomposition products are returned to the metabolism, which is the actual autophagy.
You can think of the process in simplified terms as a cleaning crew whirling around the body, sweeping up all kinds of damaged or unneeded proteins, viruses, bacteria, cell organelles, plaques and other microorganisms.
If this “pile” is complete, everything is burned and converted into vital energy. A healthy balance must be maintained in these perfectly coordinated mechanisms.
A metaphorically excessive cleansing would cause cell death, while disturbances or incomplete clean-ups can trigger serious diseases such as cancer, Alzheimer’s or Parkinson’s.
The different processes of autophagy
Christian de Duve had received the Nobel Prize 1974 for the discovery of lysosomes, among other things. At that time, the researcher had discovered with the electron microscope that different stages of decay exist in a cell, which he described at that time as autophagy. Today, three different processes are understood by autophagy.
This process serves the degradation of defective peroxisomes. These are small vesicles located in the cytoplasm of the cells that detoxify toxic metabolic products resulting from the processing of oxygen.
The mitochondria located in the cytoplasm are particularly susceptible to the toxic metabolic products of oxygen. For example, the lifespan of mitochondria in the cells of the liver, the most important detoxification organ, is just ten to twelve days. Mitophagocytosis degrades defective mitochondria and thus creates the possibilities for rejuvenation and new cell formation.
This process involves the degradation of foreign substances that penetrate the organism. These include for example viruses and bacteria.
Autophagy under the magnifying glass: The steps of cellular self-digestion
Researchers according to Duve have meanwhile succeeded in breaking down the individual steps of autophagy in detail. In the cytoplasm a double-layered membrane is formed first, the so-called phagophores. It enlarges until it encloses parts of the cytoplasm and organelles. In this process, the autophagosomes, which are completely distributed in the cytoplasm, are formed and the lysosomes lying in the direction of the cell nucleus must be transported. A kind of transport rail is available for this purpose.
Autophagosomes and lysosomes fuse together and autolysosomes are formed. Here, all components are now broken down with the help of the enzymes contained in the lysosomes.
The autophagy lysosome pathway (ALP) is one of the most important pathways for the degradation of misfolded proteins. But much more interesting is that ALP is so far the only known way to dispose of whole organelles such as mitochondria.
After this digestion process all usable parts are released into the cytoplasm. This process enables the cells to rid themselves of all harmful components and to renew themselves continuously.
The formation of the autophagosomes never stops. A certain level of activity is always present. However, there are situations where the process is running at full speed. If the organism is stressed by a lack of nutrients or harmful substances from the environment, more autophagosomes are formed.
The activity increases even in the case of a nutritional deficiency, for example due to fasting. In principle, the starving cells save themselves through self-digestion, as they feed on the substances formed in the process. This detoxification process protects the human being from many pathogens, viruses, bacteria and environmental toxins.
However, the autophagy slows down with age. If there is even a defect in this system, numerous diseases can be the result.
Autophagy is controlled by the genes
Nobel Prize Laureate Ohsumi has investigated the role of the genes involved in autophagy with yeast cells. He selected yeast cells because they show a certain correspondence with the vacuoles of mammals and thus also with those of humans.
Ohsumi now set about switching off the genes that contain the blueprint for the digestive enzymes in the vacuoles. A short time later a lot of autophagosomes accumulated, which were filled with cellular waste. Due to the lack of digestive enzymes, dissolution could no longer take place, which meant that Ohsumi had provided the proof that autophagy is genetically controlled.
Subsequently, he prepared the yeast cells with chemicals that caused genetic mutations and deactivated certain genetic traits. Afterwards, he withdrew nutrients from the yeast cells and starved them, so to speak.
In intact cells, the process of autophagy would now run at full speed due to the lack of nutrients and a swelling of the vacuoles would be observed. Only in this way would the cell be able to ensure its survival despite starvation. However, since relevant genes were deactivated, the process could not start and the vacuoles remained empty. In this way Ohsumi found 15 different hereditary traits directly linked to autophagy.
Self-digestion and suicide of the cells are close together
However, autophagy can also trigger programmed cell death, with the medical term apoptosis . Oxidative stress is capable of initiating a cellular suicide program. This is because oxidative stress leads to the formation of dangerous, reactive oxygen radicals (technical term: oxygen species). These reactive oxygen species are formed in the mitochondria. In the case of inflammatory diseases or as part of the ageing process, however, these are produced in increased quantities.
As soon as the immune system is weakened, the cells no longer have the possibility to intercept these oxygen compounds. They are released unhindered and begin their work of destruction. They damage the mitochondria both indoors and outdoors. These then release signals that lead directly to cellular suicide.
At first the cells shrink and the vesicles on the membrane become constricted. /Then the DNA fragments and the cell nucleus begins to deform. /Neighboring scavenger cells react immediately and destroy the damaged mitochondria, which would otherwise send out signals that would result in programmed cell death. This is particularly important in the brain. This is because it is not possible to simply replace damaged cells by cell division.
As you can see from this example, healthy self-digestion and cell suicide are closely related – the latter is initiated when cellular stress and damage are too great overall.
Self-healing through a functioning autophagy
Your cell function can only be maintained if the recycling works optimally. Because only when harmful material is broken down can the cell renew itself.
This is comparable to strength training. If dumbbells are lifted, small cracks appear on the muscular level. After the training, the body is first of all busy to break down all damaged muscle fragments. With the next intake of food, building blocks in the form of nutrients are available again and the muscles are built up again /strong>. This is one of the reasons why after every intensive training there should always be a rest period, so that there is time for regeneration.
Muscle breakdown and build-up must, however, be in balance so that cell purification and rebuilding merge seamlessly and no restriction of cell function takes place. This can be transferred to the entire diet. If you eat a subcalorific diet for too long or impose strict periods of fasting on yourself, the cells no longer receive enough energy and are restricted in their function. If this process is not interrupted by food intake, the cell death is induced at some point.
On the other hand, if you eat too much, insulin production is stimulated. Exactly this is one of the biggest inhibitors of autophagy. Because through the surplus your cells get the message that it is not necessary to tap the body’s own reserves. In the cells the degradation processes are slowed down and self-digestion is inhibited.
Especially carbohydrates in bread, sugar, pasta and other white flour products stimulate insulin production. Proteins and healthy fats, on the other hand, are needed by the cells to replace the already broken down components with new ones. If you deprive your cells of this possibility, the “trash” accumulates in them and the autophagy is slowed down – the cell becomes non-functional or can even degenerate.
The good news is that autophagy can be promoted by an appropriate lifestyle. The keyword for this is: intermittent fasting.
What is fasting?
The human being is not made for the permanent food supply. Because our ancestors did not have a regular meal program. What nature and the luck of the hunt provided was eaten. Especially towards the end of the winter the supply was scarce and most people had no choice but to fast.
Exactly this habit has been stored in the genes by the evolution. Fasting is a completely normal process for which the body is predisposed, while eating permanent food puts a strain on it at regular intervals.
There are numerous studies that prove the positive effect of fasting on physical health and on the mind. It is not for nothing that almost all world religions have regular periods of fasting. Fasting can help to prevent and cure diseases such as migraine, diabetes, high blood pressure, arthritis, rheumatism and even cancer.
The renunciation demands a lot from body and mind, which is why most people take time out for it. With the intermittent fasting, however, a way to health is available to everyone.
What is intermittent fasting?
Intermittent fasting is also called interval fasting . Different concepts exist. It is very common not to give the body any food at all for 14 to 16 hours, but tea and coffee with vegetable milk are allowed. The body learns its food break and reorganizes the hormone system accordingly. He tries to cover his calorie requirements no longer from the food he eats, but from his own reserves.
Dr. Satchidanada Panda of the Californian Salk Research Institute has demonstrated this effect in mice. One group of mice was fed a very high-fat diet around the clock and, as expected, developed quickly overweight and a fatty liver. A control group of “strong” people received the same amount of calories, but had to fast for 16 hours between meals – this group remained “strong” and normal weight and showed “strong” no health problems. Apparently the long break of 16 hours managed to get the body to use its own energy reserves. First the glycogen in the liver was used, then the sugar stored in the muscles and finally the fat reserves. The constantly eating group of mice only used carbohydrates for energy production, but did not burn fat.
When this group also had to fast, it was shown that these animals are equally capable of effectively burning fat.
Interval fasting activates autophagy
Autophagy is responsible for the significantly healthier fasting mice. Since the food supply was cut off during fasting, the body cells had enough time to thoroughly cleanse themselves and regenerate afterwards. Through this detoxification, the cells could remain fresh and efficient.
Panda’s research results show that apparently the insulin released after each meal is the most important factor in slowing down autophagy. This was also the conclusion reached by a group of researchers at the University of Helsinki who had studied the effect of intermittent fasting on insulin levels in men.
When does autophagy start?
Conversely, this means that autophagy is slowed down by the release of insulin. This opinion is also held by Prof. Dr. Frank Madeo from the University of Graz. This is because the temporary fasting triggers exactly the stress that the cells need to tidy up. How long it takes for the autophagy to gain momentum varies. Less than 14 hours of fasting should not be allowed under any circumstances.
The following video is a recording of a lecture by Madeo on interval fasting and autophagy:
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Colleagues from the University of Vienna confirm this. The autophagy enables the cells to survive nutritional deficiency by breaking down cellular material and thus building up new, vital proteins.
You will probably remember the recommendation to eat several small meals throughout the day to keep your blood sugar level constant. Although this makes the insulin peaks smaller, it also means that the level never drops completely. The pancreas is permanently at work, thus depriving the cells of their space for regeneration and thus autophagy.
longer young by autophagy?
If the cells are cleaned from the inside, the aging process can also be slowed down. Prof. Dr. Madeo and his team came to this conclusion in 2002 rather by chance. The researchers experimented with genes expressed in yeast. It was noticed that the yeast aged much faster in comparison when a gene product degraded the substance spermidine. The reversal experiment confirmed the assumption: Yeast cells cultivated in a medium rich in spermidine had a life span four times as long. In the next step, spermidine was added to the drinking water of flies and the fascination of scientists increased.
Support autophagy with spermidine without side effects
Even if the name suggests it, spermidin does not only occur in male sperm, but in almost all body cells. In addition, the substance is also present in a number of foods such as fresh green pepper, soy, wheat germ, mushrooms, citrus fruits and well-fermented cheese. With age, the concentration of spermidine in the body decreases – parallel to this, the capacity to break down damaged cell material decreases. Prof. Dr. Madeo and his team found out that spermidogams have the same effect as fasting. Because the result is identical – the cells begin to digest everything that is possible.
As the years go by, many harmful substances are also present. Certain proteins can be deposited and lead to neurodegenerative diseases or damaged mitochondria can promote the development of cancer. Autophagy as an anti-aging effect is activated either by fasting or by spermidine.
The study published by Madeo in 2009 triggered numerous other research projects worldwide. A Japanese study documented that spermidine works against inflammatory processes occurring in old age. Madeo himself has presented further research showing how spermidine reduces the risk of cardiovascular disease and mortality from cancer. In addition, strong spermidine helps to lower blood pressure.
According to research results from the Texas A&M University, spermidine-containing foods made animals less likely to develop liver cancer. The general life span increased by 25 %.
Studies carried out on mice have also shown that genetic muscle diseases can be cured by spermidine and dementia caused by degraded nerve cells in the forebrain. Madeo and his team used fly models to investigate the loss of memory that increases with age (dementia). This makes it possible to draw conclusions about the human brain, because memories are similarly represented in animals. By administering spermidine, the cells were given the opportunity to effectively eliminate protein wastes, which significantly improved memory performance. Even though many more studies, especially in humans, are necessary, all researchers agree that spermidine efficiently boosts autophagy and thus helps to stay young longer. In contrast to synthetic immune inhibitors such as rapamycin, spermidine does not cause undesirable side effects such as diabetes. This is because spermidine switches the program in the cell nucleus to juvenile by causing an epigenetic change. Still to be clarified is the question in which organs spermidin clears out sperm most effectively, since the individual parts of the organism age at different rates.
Longer young with spermidine-rich foods
It’s not just how you eat, it’s what you eat. Basically a Mediterranean diet is rich in spermidine. According to Madeo and his team in Graz, however, the following foods are also suitable for boosting autophagy:
Mushrooms such as mushrooms and herb seeds, wheat germ and pine nuts, fruit such as grapefruit, grapes, mangoes and apples, broccoli and green beans, ripe cheese such as cheddar, brie and parmesan, chickpeas and soya beans
For some time now, spermidine supplements have also been available, but these cannot replace a balanced diet. It is therefore best to put spermidine-rich foods regularly on the menu and preferably combine them with interval fasting.
Better autophagy through sport
Sport keeps you fit, healthy and gets the autophagy going. Various studies, including the research work of Dr. Beth Levine of the University of Dallas, also came to this conclusion. She had mice on a treadmill. As a result, sugar levels and general fitness improved. When the autophagy was artificially inhibited, the process stopped. But there is also good news for all sports enthusiasts.
Coffee promotes autophagy
The autophagy is also stimulated by coffee. This is the result of a study published in “Cell Cycle” in 2014. This does not seem to be due to caffeine, but to the polyphenols contained in coffee. This is because four hours after consuming coffee from both caffeinated and decaffeinated brands, laboratory mice showed a significantly higher rate of autophagy. By the way, this also applies to Vitamin D.
Animal protein inhibits autophagy
Animal protein on the other hand inhibits autophagy. Despite the high protein content, it is therefore better to avoid steak after sport – especially from the age of 40, because according to Prof. Madeo, excessive consumption of meat leads to a 40% higher probability of developing cancer. It is best to do sports during the fasting period. Nuts then replenish the energy stores. Again, a study conducted on 100,000 subjects over 15 years showed that regular nut consumption can reduce the mortality rate by 20%.
In a healthy organism, autophagy occurs naturally. However, if there is only the slightest disturbance in this complex mechanism and the autophagy is too fast, too slow or faulty, fatal diseases can result.
Why do these diseases pile up? Could it be that our modern lifestyle is suppressing autophagy?
Alzheimer’s, Parkinson’s and MS – diseases of the nervous system – consequence of defective autophagy ?
Alzheimer’s and Parkinson’s disease, but also Huntington’s disease can be traced back to protein deposits in the brain. These different protein aggregates are also used by physicians as diagnostic markers. For example, in Alzheimer’s disease, the protein Tau could be detected in a tissue section, while the protein responsible for Parkinson’s disease is α synuclein or alpha synuclein. In addition, in Parkinson’s disease there is also a malfunction of the lysosomes and mitochondria.
The proteins, which vary in composition depending on the clinical picture, are found in the nerve cells that serve to transmit information and the glia cells that support the central nervous system (CNS) in its work.
The glial cells themselves divide into the star-shaped astrocytes, which have a regulatory effect on the metabolism, and the oligodendrocytes.
Oligodendrocytes form the white substance myelin, which wraps around the nerve cell extensions like an insulating tape, which supports the acceleration of stimuli. In multiple sclerosis, damage to the oligodendrocytes occurs characteristically.
In order to prevent the deposition of proteins in the nerve cells, the organism has two degradation routes at its disposal. In addition to the degradation in the lysosomes, the proteasome , which is also located in the cytoplasm and in the cell nucleus, is also available for the disposal of short-lived proteins.
This protein complex (proteasome) is structured like a small barrel and literally serves as a waste bin for 80 percent of the cellular proteins. The proteasome cuts the incoming proteins into small fragments and thus enables the cell to recycle them.
Larger protein fragments cannot pass the entrance to the proteasome and are therefore recycled in the lysosomes by autophagy. Both systems are in close connection with each other.
If there is an inhibition in the lysosomes, the proteasome takes over and vice versa. Since the autophagy carries out a kind of quality control , it is problematic if the ballast of useless proteins can no longer be disposed of. This leads to the formation of protein lumps in the brain, which leads to the blockage of the cells.
Mitochondria are no longer able to migrate into the cell body and the extensions, resulting in a lack of energy supply to the cells. The result of this out-of-control recycling and self-digestion is irreversible cell death.
This was found by switching off autophagy in the brains of mice. All experimental animals showed neuronal degeneration processes typical for Alzheimer’s and an increased occurrence of protein depositions.
For comparison, the brains of Alzheimer’s patients show a high number of “strong” autophagosomes. This means that although an increased formation of vacuoles still takes place, the fusion with the lysosomes is no longer taking place or only insufficiently – the cell’s own digestion is massively disturbed and self-purification no longer functions.
A team of researchers from the University of Oldenburg was able to prove that protein deposits are found in the brains of patients suffering from multiple systemic atrophy (MSA), which are typical for a disturbed autophagy.
In the case of strong MSA, it is a disease that progresses rapidly. Symptoms include trembling, slowed movements, balance problems and problems with speaking and swallowing. In this respect, the results can also be transferred to Parkinson, because here is also found in high numbers of clumped or misfolded proteins in the nerve cells.
Since these studies cannot be carried out in humans, scientists usually have to rely on mice or rats for their studies, in which autophagy is switched off by administration of rampamycin. This is a product produced by a bacterium which, due to its immunosuppressive properties, is also used in transplants and blocks an enzyme which
In order to reduce the number of animal experiments, cell cultures have recently been increasingly used. First the protein deposits are created and then removed by the administration of Rampamycin. In addition, the substance money anamycin was able to remove deposits of alpha-synuclein in the cells typical of Parkinson’s disease by activating autophagy. Geldanamycin is usually used in cancer therapy and prevents the division of tumor cells.
In chronic obstructive pulmonary disease (COPD), the bronchial system is gradually being destroyed by the muscle cells in the bronchial system. One of the main causes of the incurable disease is cigarette smoke. A study published in “Redox Biology” in 2015 now puts COPD and a number of other lung diseases in the context of disturbed autophagy. To determine the activity of autophagy, researchers have various markers at their disposal. In the lung tissue of COPD patients there were clearly increased values. Mice suffering from COPD were observed in the laboratory for more than six months. All of them showed an increase in autophagy with a simultaneous decrease in usable proteins – which sooner or later favours the cell death of muscle cells in the bronchial tubes. So far, however, it has not been possible to completely unravel the underlying mechanism. The only thing that is certain is that the disease progressed much faster in laboratory mice when they were continuously exposed to cigarette smoke, which the researchers attribute to disturbances in autophagy.
In Crohn’s disease the immune system of the bacteria in the intestinal wall is weakened, which is obviously genetically predisposed. In the course of the chronic disease, inflammatory thickening of the intestinal wall occurs, which causes cramp-like abdominal pain and in the worst case leads to intestinal obstruction. Here too, autophagy seems to play a key role, causing a disruption of the immune system, so that bacteria present in cells can no longer be digested properly. The cells are no longer able to detoxify themselves from pollutants.
Regulation of the autophagy can also help in other intestinal diseases such as irritable bowel syndrome or colon cancer to prevent the inflammatory symptoms or generally prevent such diseases.
Does fasting help against cancer?
Fasting does not help against cancer. One can prevent by fasting, because the autophagy “cleans up” by “recycling scrap metal”. Again, there are also studies that indicate that fasting promotes cancer, but this does not logically fit in with autophagy.
“Paradoxically, most of the evidence supports a role of autophagy in maintaining tumor cell survival in response to metabolic stress in vitro and in hypoxic tumor regions in vivo. The resolution of these paradoxes related to the autophagy function has proved difficult.” (Source)
Fasting reduces side effects of chemotherapy
Fasting can reduce the harmful effects of chemotherapy. In the following video by arte, it is about (from minute 40) among other things a study in which 2 groups of mice chemotherapeutic agents were administered in an overdose. One group fasted beforehand and the other was allowed to eat normally. The fasting mice survived the chemotherapy much better than the other normally fed mice, some of which even lost their lives.
In a cancer clinic, some patients fasted for 48 hours before chemotherapy and thus survived the chemotherapy much better, the side effects were less pronounced. There was an overall reduction in fatigue, weakness and gastrointestinal side effects.
How do you explain this?
Chemotherapeutic agents normally attack all cells of the body, they do not make a difference. After two days of fasting, normal healthy cells enter a protection mode in which they multiply less rapidly and which protects them from the devastating effects of chemotherapy. Cancer cells can’t do that. Cancer cells expand rigorously.
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Interval fasting for the intestinal flora
In the blog article “Interval fasting for the intestinal flora” I explain the background, studies etc.
By using relatively simple means such as a careful selection of your food, a sports program and intermittent fasting, you have a wonderful opportunity to do something for your health – without any side effects. In this way, you make an important contribution to the prevention of numerous diseases and the natural aging process, as you help your cells to thoroughly eliminate toxins and other waste products.
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