Autophagy is a natural cellular process in eukaryotes — cells with membrane-bound organelles. It's the regulated, destructive process in which a cell eliminates components that are unnecessary or not working correctly. Scientists have limited understanding of how autophagy works, but it has attracted a lot of attention as a way to treat or cure disease.
Studies show that the regulation of autophagy is very complicated. In many cells, amino acid depletion seems to induce autophagy, though each amino acid has a different effect. Leucine, for instance, predominantly affects skeletal and cardiac muscle. The exact mechanism used by the body to control this response is unknown, but researchers speculate that insulin and the endocrine system play a big role.
Starvation is the most common trigger of autophagy, and lack of any nutrient can start the process. Studies on yeast show that starvation results in the most efficient autophagy, but withholding amino acids, sulfate, and carbon would also induce it. In humans, autophagy can be a defense mechanism against stressors, such as a lack of nutrients, aging, or disease.
The first phase in autophagy is sequestriation. A unique membrane forms called a phagophore, enclosing organelles or other components of the cell that need eliminating. Once the phagophore completely encapsulates the object, an autophagosome forms. Autophagosomes typically have a double membrane and, depending on the size, may be visible as a ring under an electron microscope. There is no degradation in this phase. Sequestration is about isolating and encapsulating the elements that need eliminating.
Degradation is the next phase of autophagy. In it, autophagosomes fuse with lysosomes, organelles containing enzymes that break down components of the cell. Some researchers speculate that endosomes, the organelles that transport molecules inside the cell, are involved in this process as well. This process is difficult to measure and evaluate, even under electron microscopy, so experts still have a lot to learn.
The final phase of autophagy is utilization. Little is known about this phase, but researchers believe that the cell transports components that have been broken down to the cytosol or intercellular fluid for reuse. Researchers believe that cells use this process with amino acids, but whether cells can reuse lipids or carbohydrates is unknown.
Nearly all cells perform autophagy to maintain health and balance. The process is essential for turning over organelles or during starvation states when cells need to create their own energy and nutrients. Researchers believe that a number of factors influence autophagy, including nutrition, stress, infection, oxygen levels, and cell density.
Knowing that a lack of amino acids and nutrition influences autophagy has led researchers to examine the effects of intermittent fasting on aging and age-related diseases. Animal studies involving flies, worms, and rodents suggest that intermittent fasting lengthens the life span; the resulting autophagy affects many age-related diseases in these animals, including Huntington's disease and cancer.
Because autophagy is the body's natural way of eliminating the unnecessary or dysfunctional parts of every cell, researchers are now interested in the relationship between autophagy and disease. Studies show that some diseases relate to autophagy, including gastrointestinal and respiratory diseases, while others — such as developmental and skin diseases and those of the ear, nose, and throat — do not.
Research about autophagy and cancer cells is not conclusive. Some studies show that cancer cells use autophagy to survive. Others show that inhibiting autophagy improves the effectiveness of cancer treatments. The details of how this natural process contributes to cancer are still unclear, but understanding the relationship is an area of significant interest. Autophagy plays a diverse role in cancer, both contributing to its growth and protecting against it.
Autophagy is an area of interest for many reasons, including its role in maintaining cellular health, the cellular reaction to stress and disease, and its relationship to intermittent fasting. That said, using autophagy as therapy is not without risk. The process can kill cells that should live and sustain those that should die. Further research can teach medical professionals more about benefits, risks, and the potential of autophagy as a future treatment for disease.
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