The Belgian scientist Christian de Duve was awarded the Nobel Prize in Physiology or Medicine in 1974 for the discovery of the lysosome. The lysosome contained enzymes specifically for the digestion and degradation of cellular contents. Further biochemical and microscopic analysis of this cell revealed a new type of vesicle as well. You can think of vesicles as cellular envelopes used to transport materials from one place to another. Vesicles transferring material is not unusual but In this case the purpose of delivering this cargo for degradation. de Duve coined the term autophagy or “self-eating”, to describe this process. The new vesicles were named autophagosomes.
As these autophagosome are formed they engulf cellular contents, such as damaged proteins and organelles. It’s final function is to fuse with the lysosome, where the contents are degraded into smaller constituents. This process provides the cell with nutrients and building blocks for renewal of cells. In other words when autophagosomes are able to work, they eat the bad cells and turn them into the foundation of new cells; A quality control mechanism that is critical for counteracting the negative consequences of aging.
You may have heard the term autophagy when discussing fasting. Fasting is NOT also called autophagy. Fasting is just the fastest way to trigger autophagy. Nutrient deprivation is the key activator of autophagy. If insulin (a protein pancreatic hormone essential for the metabolism of carbohydrates) goes down, glucagon (a protein hormone promotes an increase in the sugar content of the blood by increasing the rate of glycogen breakdown in the liver) goes up.
As we eat, insulin goes up and glucagon goes down. When we don’t eat (fast) insulin goes down and glucagon goes up. When we don’t eat, it’s easier for our autophagosomes to eat the damaged and proteins and organelles as it’s important that cellular components be degraded and recycled. Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components. It is therefore essential for the cellular response to starvation and other types of stress. After infection of a cell, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy also contributes to embryo development and cell differentiation.
Disrupted autophagy has been linked to Parkinson’s disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer. Intense research is now ongoing to develop drugs that can target autophagy in various diseases.
This is in essence a form of cellular cleansing. The body identifies old and substandard cellular equipment and marks it for destruction. It is the accumulation of all this junk that may be responsible for many of the effects of aging.
Fasting is actually far more beneficial than just stimulating autophagy. It does two good things. By stimulating autophagy, we are clearing out all our old, junky proteins and cellular parts. At the same time, fasting also stimulates growth hormone, which tells our body to start producing some new snazzy parts for the body.
So the process of destruction (removal) is just as important as the process of creation.
So, during autophagy, old cell components are broken down into the component amino acids (the building block of proteins). What happens to these amino acids? In the early stages of starvation, amino acid levels start to increase. It is thought that these amino acids derived from autophagy are delivered to the liver for gluconeogenesis. They can also be broken down into glucose through the tricarboxylic acid (TCA) cycle. The third potential fate of amino acids is to be incorporated into new proteins.
The consequences of accumulating old junky proteins all over the place can be seen in two main conditions — Alzheimer’s Disease (AD) and cancer. Alzheimer’s Disease involves the accumulation of abnormal proteins — either amyloid beta or Tau protein which gums up the neurological system. It would make sense that a process like autophagy that has the ability to clear out old protein could prevent the development of AD.
What turns off autophagy? Eating. Glucose, insulin (or decreased glucagon) and proteins all turn off this self-cleaning process. And it doesn’t take much. Even a small amount of amino acid (leucine) could stop autophagy cold. So this process of autophagy is unique to fasting — something not found in simple caloric restriction or dieting.
There is a balance here, of course. You get sick from too much autophagy as well as too little. Which gets us back to the natural cycle of life — feast and fast. Not constant dieting. This allows for cell growth while eating, and cellular cleansing during fasting — balance. Life is all about balance.
