Yoshinori Ohsumi was awarded the Nobel Prize in Physiology or Medicine in 2016 by the Nobel Assembly at Karolinska Institutet for his discoveries of autophagy mechanisms.
But what exactly is autophagy? The term is derived from the Greek words auto (self) and food to eat. As a result, time means “to consume oneself.” This is the body’s way of getting rid of all the broken down, old cell machinery (organelles, proteins, and cell membranes) when there isn’t enough energy to sustain it. Degradation and recycling of cellular components is a controlled, organized process.
Apoptosis, also known as programmed cell death, is a comparable, more well-known phenomenon. Cells are programmed to die after a particular number of divisions. While this may appear to be a morbid process at first, keep in mind that it is necessary for healthy health. Consider the following scenario: you own an automobile. You adore this vehicle. It holds a lot of memories for you. You enjoy riding it.
However, after a few years, it begins to look worn. After a couple more, things aren’t looking so well. The car costs you thousands of dollars to maintain each year. It’s constantly breaking down. Is it preferable to keep it around when it’s just a piece of junk? Clearly not. So you sell it and get a flashy new car.
In the body, the same thing occurs. Cells age and degrade. It is preferable if they are set to die when their useful life is through. It may appear to be cruel, but such is life. That is the apoptosis process, in which cells are programmed to die after a set amount of time. It’s similar to leasing a car. You get rid of the car after a specific amount of time, whether it’s still running or not. After that, you get a new car. You don’t have to be concerned about it breaking down at the most inconvenient time.
Autophagy is the process through which aged portions of the cell are replaced.
The same thing happens at the subcellular level. You do not have to replace the complete vehicle. Sometimes all you need to do is replace the battery, toss away the old one, and get a new one. This also occurs within cells. Instead of destroying the complete cell (apoptosis), you want to replace certain of its components. That is the autophagic process, in which subcellular organelles are destroyed, and new ones are created to replace them. It is possible to eliminate old cell membranes, organelles, and other cellular detritus. This is accomplished by delivering it to the lysosome, a specialized organelle that contains enzymes that destroy proteins.
Autophagy was initially identified in 1962 when researchers saw an increase in the number of lysosomes (the component of the cell that kills things) after injecting glucagon into rat liver cells. The word “autophagy” was invented by Nobel laureate Christian de Duve. Damaged subcellular components and unneeded proteins are identified for elimination and subsequently delivered to the lysosomes to complete the task.
The mammalian kinase target of rapamycin is a critical regulator of autophagy (mTOR). When engaged, mTOR suppresses autophagy; when inactive, it stimulates it.
What causes autophagy to occur?
Autophagy is primarily activated by nutrient restriction. Remember that glucagon is the hormone that works in the opposite direction of insulin. It’s similar to the game we used to play as kids called ‘opposite day.’ When insulin levels rise, glucagon levels fall. When insulin levels fall, glucagon levels rise. As we eat, insulin rises, and glucagon falls. When we don’t eat (fast), insulin drops, and glucagon rises. This rise in glucagon activates the autophagic process. Fasting (which increases glucagon) provides the most significant available boost to autophagy.
Fasting is significantly more helpful than simply activating autophagy. It serves two purposes. We are sweeping out all of our old, junky proteins and cellular pieces via promoting autophagy. Simultaneously, fasting promotes growth hormone, which instructs our bodies to generate some new stylish body parts. We’re genuinely giving our bodies a thorough makeover.
Before you can put in new items, you must first remove the existing ones. Consider remodeling your kitchen. If you have old 1970s style lime green cabinets lying around, you should get rid of them before installing new ones. As a result, the process of elimination (destruction) is just as significant as creation. It wouldn’t look so good if you just put in new cabinets without removing the old ones. As a result, fasting may help reverse the aging process by removing old cellular trash and replacing it with fresh pieces.
A meticulously planned procedure
Autophagy is a tightly controlled process. It would be damaging if it ran amok, out of control. Thus it must be appropriately maintained. Total amino acid depletion is a significant signal for autophagy in mammalian cells, while the effect of specific amino acids is more varied. The plasma amino acid levels, on the other hand, alter just slightly. Amino acid and growth factor/insulin signals are expected to converge on the mTOR pathway, also known as the master regulator of nutritional signaling.
As a result, aged cell components are broken down into amino acids (the building block of proteins). What becomes to these amino acids? Amino acid levels begin to rise during the early stages of hunger. These amino acids generated from autophagy are expected to be transported to the liver for gluconeogenesis. They can also be converted to glucose via the tricarboxylic acid (TCA) cycle. The incorporation of amino acids into new proteins is the third possible fate of amino acids.
The effects of collecting old junky proteins all over the place can be seen in two significant conditions: Alzheimer’s Disease (AD) and malignancy. Alzheimer’s disease is caused by the buildup of aberrant protein – either amyloid-beta or Tau protein – in the brain, which clogs the system. Although there is no clinical trial proof for this, it would seem logical that a mechanism like autophagy, which can sweep out old protein, could help prevent the development of Alzheimer’s disease.
What inhibits autophagy? Eating. This self-cleaning process is hindered by glucose, insulin (or reduced glucagon), and proteins. And it isn’t difficult. Even a trace amount of an amino acid (leucine) can halt autophagy. As a result, this autophagy process is unique to fasting and is not simple caloric restriction or dieting.
Of course, there is a balance here. You can become ill from both too much and too little autophagy. That brings us back to the natural cycle of life – feasting and fasting. I am not dieting all the time. This allows for cell growth while eating and cellular cleansing while fasting – a state of balance. Life is all about finding the right balance.