What is Autophagy?

The article describes the science behind, benefits of and where autophagy works in our bodies.

Autophagy is a highly conserved process of breaking down damaged cells within the body. By activating the Atg genes responsible for self-cleanup, it can consume organelles such as mitochondria and the endoplasmic reticulum. Additionally, it enhances the acetylation process by suppressing the expression of specific proteins. Fasting induces autophagy; interestingly, spermidine also induces autophagy, similar to fasting. This leads to the development of autophagosomes, which are the components of the cell that take up and degrade undesirable material. (Madeo, Bauer, et al., 2018)

How does autophagy work?

Before a misfolded protein in a cell can be degraded, it must be isolated from the rest of the cell. Otherwise, the proteases would also break down useful components of the cell.

The isolation membrane, also known as the phagophore, divides the target protein from all other substances. To create an autophagosome, this double membrane encircles the protein. This is known as the autophagosome, which then travels to the lysosome. The autophagosome attaches to a nearby lysosome to form the autolysosome.

Now that the protein is in the presence of proteases, it can be broken down into amino acids. After digestion, the amino acids are removed for recycling by transporters and proteases. (Bento et al., 2016)

In general, let's consider the autophagosome as a tiny drop that surrounds the protein. After that, it unites with another drop called a lysosome to form an autolysosome. Then the protein splits into smaller fragments. To enable these fragments to be utilized in the construction of new structures, other proteins help move them.

Where and how does it work in the human body?

1. Liver: One important location for autophagy is the liver. By aiding in the breakdown of damaged proteins and organelles, it supports the processes involved in detoxification and metabolic homeostasis. (Rautou et al., 2010)

2. Brain: Neuronal health depends on autophagy. It assists in eliminating misfolded proteins and damaged cellular elements that could be connected to neurodegenerative illnesses like Parkinson's and Alzheimer's. (Keller et al., 2004b)

3. Muscles: To maintain appropriate muscle function and strength, muscle cells use autophagy to remove malfunctioning mitochondria. (Grumati et al., 2011)

4. Heart: Autophagy plays a critical role in maintaining the health of the heart muscle cells by facilitating the removal of damaged proteins and organelles, which improves heart function and helps prevent heart disease. (Sciarretta et al., 2018)

5. Immune system: By eliminating pathogens and facilitating the presentation of antigens to immune cells, autophagy contributes to the regulation of the immune response. (Kuballa et al., 2012)

6. Adipose tissue: Autophagy contributes to the maintenance of adipose tissue function by assisting in the regulation of lipid metabolism in fat cells. (Zhang et al., 2012)

Benefits of Autophagy

Autophagy affects both the internal and external parts of the cell.

Within the cell, autophagy can help

1. Reduce oxidative stress.

2. Maintain the stability of genes and DNA.

3. Prevent cells from ageing and deteriorating too soon.

4. Maximize the energy yield from nutrients.

5. Enhance the removal of waste.

6. Remove pathogens and other foreign objects from cells.

7. Remove harmful substances to help prevent the formation of tumours.

Outside of the cell, autophagy can help

1. Reduce the degree of inflammation.

2. Boost the brain's ability to transmit nerve signals.

3. Maintain healthy immune system function.

In a nutshell, autophagy helps the overall well-being of the human body by acting as an inhibitor of tumours, slowing down ageing, and promoting longevity.

Ways to simulate Autophagy in the body

• Fasting: A highly effective way to initiate autophagy is through fasting. The body goes into an autophagic state to recycle cell components for energy when it is starved, especially for prolonged periods.

• Keto Diet: A ketogenic diet, which is high in fat and low in carbs, may also induce autophagy. By shifting the body's energy source from glucose to ketones, it may stimulate autophagy.

• Exercise: Regular physical activity, especially high-intensity exercises, can promote autophagy. Exercise-induced stress can trigger the cell's autophagic process, which helps the body repair itself by removing damaged components.

• Certain Foods and Nutrients: Some foods and compounds are believed to support autophagy. For example, green tea, turmeric, resveratrol found in red grapes, and foods rich in polyphenols and antioxidants.

• Supplements: Certain supplements, like spermidine, have been studied for their potential to induce autophagy.

References:

1. Madeo, F., Bauer, M. A., Carmona-Gutiérrez, D., & Kroemer, G. (2018b). Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans? Autophagy, 15(1), 165–168. https://doi.org/10.1080/15548627.2018.1530929
2. Bento, C. F., Renna, M., Ghislat, G., Puri, C., Ashkenazi, A., Vicinanza, M., Menzies, F. M., & Rubinsztein, D. C. (2016). Mammalian Autophagy: How Does It Work? https://doi.org/10.1146/annurev-biochem-060815-014556
3. Rautou, P., Mansouri, A., Lebrec, D., Durand, F., Valla, D., & Moreau, R. (2010).Autophagy in liver diseases. Journal of Hepatology, 53(6), 1123–1134. https://doi.org/10.1016/j.jhep.2010.07.006
4. Keller, J. N., Dimayuga, E., Chen, Q., Thorpe, J., Gee, J., & Ding, Q. (2004). Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. The International Journal of Biochemistry & Cell Biology, 36(12), 2376-2391. https://doi.org/10.1016/j.biocel.2004.05.003
5. Keller, J. N., Dimayuga, E., Chen, Q., Thorpe, J., Gee, J., & Ding, Q. (2004). Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. The International Journal of Biochemistry & Cell Biology, 36(12), 2376-2391. https://doi.org/10.1016/j.biocel.2004.05.003
6. Grumati, P., Coletto, L., Schiavinato, A., Castagnaro, S., Bertaggia, E., Sandri, M., & Bonaldo, P. (2011). Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles. Autophagy, 7(12), 1415-1423. https://doi.org/10.4161/auto.7.12.17877
7. Sciarretta, S., Maejima, Y., Zablocki, D., & Sadoshima, J. (2018). The Role of Autophagy in the Heart. https://doi.org/10.1146/annurev-physiol-021317-121427
8. Kuballa, P., Nolte, W. M., Castoreno, A. B., & Xavier, R. J. (2012). Autophagy and the Immune System. https://doi.org/10.1146/annurev-immunol-020711-074948
9. Zhang, Y., Zeng, X., & Jin, S. (2012). Autophagy in adipose tissue biology.Pharmacological Research, 66(6), 505–512. https://doi.org/10.1016/j.phrs.2012.09.004