How to renew your body: Fasting and autophagy
In 2016, the Nobel Assembly at Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy.
But what is autophagy? The word derives from the Greek auto (self) and phagein (to eat). So the word literally means to eat oneself. Essentially, this is the body’s mechanism of getting rid of all the broken down, old cell machinery (organelles, proteins and cell membranes) when there’s no longer enough energy to sustain it. It is a regulated, orderly process to degrade and recycle cellular components.
There is a similar, better known process called apoptosis also known as programmed cell death. Cells, after a certain number of division, are programmed to die. While this may sound kind of macabre at first, realize that this process is essential in maintaining good health. For example, suppose you own a car. You love this car. You have great memories in it. You love to ride it.
But after a few years, it starts to look kind of beat up. After a few more, it’s not looking so great. The car is costing you thousands of dollars every year to maintain. It’s breaking down all the time. Is it better to keep it around when it’s nothing but a hunk of junk? Obviously not. So you get rid of it and buy a snazzy new car.
The same thing happens in the body. Cells become old and junky. It is better that they be programmed to die when their useful life is done. It sounds really cruel, but that’s life. That’s the process of apoptosis, where cells are pre-destined to die after a certain amount of time. It’s like leasing a car. After a certain amount of time, you get rid of the car, whether it’s still working or not. Then you get a new car. You don’t have to worry about it breaking down at the worst possible time.
Autophagy – replacing old parts of the cell
The same process also happens at a sub-cellular level. You don’t necessarily need to replace the entire car. Sometimes, you just need to replace the battery, throw out the old one and get a new one. This also happens in the cells. Instead of killing off the entire cell (apoptosis), you only want to replace some cell parts. That is the process of autophagy, where sub-cellular organelles are destroyed and new ones are rebuilt to replace it. Old cell membranes, organelles and other cellular debris can be removed. This is done by sending it to the lysosome which is a specialized organelle containing enzymes to degrade proteins.
Autophagy was first described in 1962 when researchers noted an increase in the number of lysosomes (the part of the cell that destroys stuff) in rat liver cells after infusing glucagon. The Nobel prize winning scientist Christian de Duve coined the term autophagy. Damaged sub cellular parts and unused proteins become marked for destruction and then sent to the lysosomes to finish the job.
One of the key regulators of autophagy is the kinase called mammalian target of rapamycin (mTOR). When mTOR is activated, it suppresses autophagy, and when dormant, it promotes it.
What activates autophagy?
Nutrient deprivation is the key activator of autophagy. Remember that glucagon is kind of the opposite hormone to insulin. It’s like the game we played as kids – ‘opposite day’. If insulin goes up, glucagon goes down. If insulin goes down, glucagon 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. This increase in glucagon stimulates the process of autophagy. In fact, fasting (raises glucagon) provides the greatest known boost to autophagy.
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. We are really giving our bodies the complete renovation.
You need to get rid of the old stuff before you can put in new stuff. Think about renovating your kitchen. If you have old 1970s style lime green cabinets sitting around, you need to junk them before putting in some new ones. So the process of destruction (removal) is just as important as the process of creation. If you simply tried to put in new cabinets without taking out the old ones, it wouldn’t look so hot. So fasting may in some ways reverse the aging process, by getting rid of old cellular junk and replacing it with new parts.
A highly controlled process
Autophagy is a highly regulated process. If it runs amok, out of control, this would be detrimental, so it must be carefully controlled. In mammalian cells, total depletion of amino acids is a strong signal for autophagy, but the role of individual amino acids is more variable. However, the plasma amino acid levels vary only a little. Amino acid signals and growth factor / insulin signals are thought to converge on the mTOR pathway – sometimes called the master regulator of nutrient signalling.
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 protein – either amyloid beta or Tau protein which gums up the brain system. Although we don’t yet have clinical trial evidence for this, 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 during eating, and cellular cleansing during fasting – balance. Life is all about balance.
—
Jason Fung
More
Want to give fasting a try? Check out our complete beginner’s guide:
Intermittent fasting for beginners
Popular videos about fasting
Earlier with Dr. Jason Fung
How Much Protein Should You Eat?
The Common Currency in Our Bodies Is Not Calories – Guess What It Is?
Why the First Law of Thermodynamics Is Utterly Irrelevant
How to Fix Your Broken Metabolism by Doing the Exact Opposite
More with Dr. Fung
Dr. Fung has his own blog at intensivedietarymanagement.com. He is also active on Twitter.
His book The Obesity Code is available on Amazon.
117 comments
https://www.youtube.com/watch?v=d6PyyatqJSE
I haven't found another site on Yoshinori Ohsumi that talks about using fasting as a technique, however. One site says, "It could give us a way to make Parkinson’s disease drugs that work by controlling autophagy.... It could provide new ways of fighting Diabetes and a host of other diseases. Of course, those advancements are still some ways off."
http://futurism.com/self-cannibalization-nobel-prize-in-medicine-goes...
Sheesh!
Dr. Longo is talking about refeeding as part of the process, interesting.
1) Drinking green tea.
2) Taking PQQ (found in green tea) (take along with a little fat, and with some CoQ10 for best results)
3) Green tea polyphenols have been shown to induce cell death (apoptosis) in prostate cancer cells, breast cancer cells and other cancer cells.
4) Taking quercetin along with resveratrol.
5) Partial fasts: avoiding carbohydrates.
6) Partial fasts: avoiding protein for a few days (see Valter Longo's research)
7) Exercise.
8) Exercise while fasting (about two hours before a meal)
I don't mean to sound negative but either one of two things is happening:
1. The author's of this website are toying with your emotions by over-exaggerating claims to make themselves sound confident and therefore get you to believe them
or
2. they searched the web for "scientific studies" using the words "decrease" and "autophagy" and just linked it to this post to make it seem like they have done extensive research knowing full well the majority of people on here wouldn't understand anything the study is saying.
Either way, i just ask the genuine visitors to this site be careful on what you believe as "scientific fact"
"And it doesn’t take much. Even a small amount of amino acid (leucine) could stop autophagy cold. "
In layman's terms.. to your brain Tim, "could" means the exact same as "will".
and you mistake my intentions, I am merely trying to point out that the vast majority of people who read "could stop autophagy cold" if you take any amino acid will most likely take it as a 100% true scientific fact and avoid any trace of amino acids during fasting for as long as they live... and that shouldnt be the case.
All I am asking is that just because there is a "Dr." in front of someone's name doesn't mean you should have blind faith in what they say. Trust but verify.
Obviously it doesn't, since I pointed it out...and the definition of 'fasting' is not to eat anything. Amino acids, or otherwise...so your point is moot.
Your misquote was obvious...and off topic, since the article was about fasting to induce autophagy. Raise insulin, decrease glucagon - decrease autophagy...lower insulin, increase glucagon - increase autophagy. A sliding scale...It's all right there in the article.
What I have been reading about LCHF diets point exclusively to eating foods high in fat and protein (meats, cheeses, etc.) and avoiding starches, sugars, bread, pasta, etc., and pretty much leads me to believe that beer and wines are mostly out.
I have seen in recent labs that I have developed an insulin resistance, albeit small (according to my doctor), but suffer extreme fatigue after meals (short lived), that often seem to be remedied by sugar intakes. Not sure why that is, but it is.
I also have this spare tire at 49 that has seemed incorrigable, and I have plans for retirement so I feel like I need to get serious about adopting a plan that is going to deliver me to the best physical and mental states that I can exist in, and LCHF seems to be the way to go.
I welcome any input folks have.
More, a recent article has shown that fasting resulted in reduction of the cyst size in polycystic kidney disease mice, while this did not occur in mice on normal diet!!
Fast, any time you can!
Maria Jasmine Freeman
I know that, Muslims must fast the whole day time during the holy month of Ramadan besides some optional days during the week.
It seems to my they are right about fasting.
The question is what kind of fasting and for how many hours.
Everyday we discover amazing things about Islam in spite of all trials to distort it
Prophet Muhammad (PBUH) emphasized the habit of eating less as a method of preventing sickness and disease. Prophet Muhammad (PBUH) said:
“Nothing is worse than a person who fills his stomach. It should be enough for the son of Adam to have a few bites to satisfy his hunger. If he wishes more, it should be: One-third for his food, one-third for his liquids, and one-third for his breath.”
– Tirmidhi & Ibn Majah
** " from the article i read, it said the "breath" may refer to the gas that emitted from the food" (Allah knows best)
https://religionatlums.wordpress.com/about/eating-habitssunnah-of-the...
https://www.al-islam.org/message-thaqalayn/vol-14-no-2-summer-2013/ea...