Recycling in the cell (autophagy) is important to generate energy and to produce new cellular units. What is interesting, though, is that autophagy is primarily activated via fasting.

With all of its faculties, a human being can be thought of as an index of the whole universe. Therefore, we witness correlations between the processes taking place in the human body and in the universe. Accordingly, the world we live in has a correspondence to human biology. For example, the cyclical processes in the environment (water cycle, carbon cycle, etc.) ensure the continuous recycling of the same matter, hence the cleanliness of the habitat for all. Similarly, the human body includes mechanisms to cleanse itself from harmful and unnecessary materials.

Prior to the development of such an understanding, the prevailing attitude encouraged consuming natural resources and using the environment as a "trash can." Even today, we live in a world that promotes excessive consumption of daily goods leading to accumulation of incredible amounts of trash. For example, in developed Western societies, an average family discards more than one ton of trash every year, which is mostly paper, packaging material, and kitchen waste.

Nevertheless, as we realize the importance of the recycling systems in nature and the multi-faceted harms of trash accumulation on the environment, recycling of conventional and technological waste is encouraged by collecting plastics, glass, paper, and tins. On a larger scale, recycling centers have been developed to minimize the damage to the environment and to meet the need for raw materials.

The recycling process consists of three main steps as depicted by the famous three-arrows symbol representing 1) the collection of materials, 2) the remanufacture of new materials from the collected ones, and 3) reselling or reusing as new products. Thus, recycling centers not only contribute to the economy, but also serve as clearance sites to maintain the harmony of the environment.

Cellular recycling through "fasting"

Similar to recycling centers at the macro level, there are recycling centers in the cellular level too. These centers have the duty to help with the digestion of cellular trash (i.e. damaged cellular organelles, misfolded proteins, toxic load) so that energy can be generated and raw material obtained for the construction of new cellular units. This recycling phenomenon was simply named as autophagy (i.e. self-eating) by cell biologists. What is interesting, though, is that autophagy is primarily activated or enhanced via fasting or food deprivation.

How autophagy works

Autophagy is a process that occurs when astarving cell starts to form double membrane containers through an orchestration of several proteins. These containers are called autophagic vesicles or autophagosomes 1. Their main role is to target and collect cellular trash. Then, they start to fuse with lysosomes, the digestion centers of the cells, to degrade the trash into building blocks—amino acids. The amino acids can then be used both for the construction of new proteins needed by the cell and in the production of ATP, which is a source of energy for the cell.

The whole process corresponds to micro-scale representation of a real world recycling concept: collection, re-manufacture and resell/reuse. Through autophagy, a cell recycles its own material and obtains energy 2.

Fasting: an emerging trend

With the discovery of mechanisms initiating autophagy and its involvement in various diseases such as cancer, neurodegenerative disorders, auto-immune diseases etc., autophagy has gained a unique significance that is progressively increasing 3. After the year 2000, the number of publications on autophagy-related research began to increase exponentially. Moreover, due to the increased conviction about the link between fasting and autophagy, fasting started to become a real trend in modern civilizations. Let's examine a few of the important recent findings that reveal the relationship between autophagy and fasting.

In a study involving mice, the response to fasting was assessed in liver cells (hepatocytes) by tracking the presence of a protein (GFP-LC3) that indicates autophagy. It was seen that the lack of food, which is the source of energy, led to the disintegration of mitochondria, which are the power plants of the cells. Subsequently, the components that made up those mitochondria were re-utilized for the building of other necessary proteins4. These results indicate that unnecessary mitochondria were eliminated for the sake of recycling organic materials during fasting.

Neurodegenerative diseases, such as Alzheimer's or Parkinson, etc, are linked to the accumulation of trash in the brain cells, which is indicative of a lack of autophagy. Drugs developed for these diseases do not possess effective treatments since they are unable to penetrate into the brain cells (a concept known as the blood-brain barrier). During another study involving mice, in one track, animals were exposed to fasting, and in the other, their brain cells, (more precisely cortical neurons and Purkinje cells) were isolated and exposed to food deprivation. In both tracks, researchers observed that fasting enhanced autophagy, suggesting that fasting could be a simple, cheap, and safe therapeutic cure for prevention of neurodegenerative diseases 5.

In another study, this time involving a subset of kidney cells (proximal tubule cells), a lack of autophagy resulted in the accumulation of dysfunctional mitochondria and other cellular debris. As a result, the cells grew in size abnormally (hypertrophy), decreasing the functionality of the kidney. This suggested that autophagy was part of the continuous maintenance of proximal tubule cells and that inducing autophagy in the kidney may provide a novel therapeutic approach to minimize acute kidney injury 6.

As a final example, one more study revealing the association between autophagy and the immune response should be mentioned. It was found that the number of autophagic vesicles (chambers) in the macrophages, a subset of immune cells that are the first to perceive threats to our body, increased as a response to invading bacteria. These vesicles wrapped, sequestered, and digested the bacteria eaten by macrophages 7. Thus, fasting has the potential to improve the fighting ability of macrophages against invading pathogens by enhancing autophagic machinery.

Taken together, the autophagy process seems to be a recycling mechanism with minor variations depending on the cell type and activation triggers. Once initiated, it leads to a) reduced accumulation of cellular trash (toxic protein aggregates); b) an improved immune response for removing bacteria (intracellular pathogens); and c) the protection of the interior of the cell (cytosol). As one of the main stimulators of autophagy, fasting or food deprivation seems to be a way for improving health.

Next time you fast, keep in mind that while you are starving, your cells are feasting for your health. Just as the natural world is structured to continually cleanse and renew the earth, fasting seems to trigger similar processes inside the human body. While individuals may choose to fast for spiritual cleansing, their physical bodies experience a cleansing as well.

Abdullah Acar is freelance writer in the US with a special interest in biology.


References

1.Mizushima, N., et al., Autophagy fights disease through cellular self-digestion. Nature, 2008. 451(7182): p. 1069-75.

2.Mizushima, N. and M. Komatsu, Autophagy: renovation of cells and tissues. Cell, 2011. 147(4): p. 728-41.

3.Yang, Z. and D.J. Klionsky, Eaten alive: a history of macroautophagy. Nat Cell Biol, 2010. 12(9): p. 814-22.

4.Kim, I. and J.J. Lemasters, Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation. Am J Physiol Cell Physiol, 2011. 300(2): p. C308-17.

5.Alirezaei, M., et al., Short-term fasting induces profound neuronal autophagy. Autophagy, 2010. 6(6): p. 702-10.

6.Kimura, T., et al., Autophagy protects the proximal tubule from degeneration and acute ischemic injury. J Am Soc Nephrol, 2011. 22(5): p. 902-13.

7.Fujita, N. and T. Yoshimori, Ubiquitination-mediated autophagy against invading bacteria. Curr Opin Cell Biol, 2011. 23(4): p. 492-7.

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