#59 All About Autophagy

Siim Land (0:00)

Psst, quick, I just have to share with you this story about Frank. You see, one day, Frank was starving, and then he ate himself. Now, Frank is still alive, and he's even stronger than before.

This is because of a cellular pathway called autophagy. Welcome to the Body Mind Empowerment Podcast. I'm a host, Siim Land, and in this episode, I'm gonna explain to you what is autophagy, and how it can help you to live a longer and healthier life.

SPEAKER_2 (0:38)

Do you want to know what it is?

Siim Land (0:42)

Body Mind Empowerment.

SPEAKER_2 (0:43)

Get stronger, faster, smarter, quicker, friendlier, more helpful, more driven.

Siim Land (0:49)

Everything the body needs.

SPEAKER_2 (0:51)

Control your mind.

Siim Land (0:55)

When we know one thing, then it is that we don't know much about autophagy, but we still know something about it. So this is what we know about autophagy so far. So what is autophagy? Autophagy, or if we use like fancy science language, autophagocytosis, it translates from the ancient Greek word autophagus, which means self-digestion or eating of self.

It's almost like self-cannibalism. Autophagy is a metabolic process during which cells disassemble and remove their dysfunctional components.

You're gonna basically recycle cellular debris and you're taking out the trash. During the first findings, it was thought that autophagy was a hormonal response to starvation, but recent research has shown that autophagy has many other roles in biology. There are many benefits to autophagy, such as reduction in inflammation, improved immune system, prevention of genotoxic stress, anti-aging and longevity, suppression of cancerous tumor cells, elimination of infectious pathogens and toxins, and overall youthfulness. Inability-caused autophagy has been shown to make rats fatter, less active, have higher levels of cholesterol and impaired brain function. Compromised autophagy pathways, they're gonna lower the body's ability to eliminate and heal the organism from inflammation, accumulation of toxins and parasitic infections.

Autophagy is also quite a new thing in medicine and science. On the 3rd of October, 2016, a Japanese researcher Yoshinori Oshumi was rewarded the Nobel Prize in Physiology or Medicine for, quote, discoveries of the mechanisms for autophagy. His research is done in simple organisms like baker's yeast, but the autophagy-related pathways, they've been found to be similar to autophagy in mammals and humans as well. So how does it work? When autophagy gets activated, the organelles of your healthy cells, they start to hunt out dead or diseased cells, and then they consume them. They eat them alive. It's the survival of the fittest inside your body, or much rather survival of the most healthiest.

Autophagy is mediated by an organelle called the autophagosome, which combines with other cellular components like the endosome and lysosome. These parts, they're going to form a double membrane around a cell that's going to be eaten. The autophagosome then dissolves the cell that is sentenced to death.

It's literally like your organism's fight club, where they selectively select out the weak ones and they're going to beat them to death.

Where and how the autophagosome gets formed is currently a mystery for researchers.

In yeast, it's been identified to occur when many ATG proteins converge. ATG proteins are autophagy-related proteins. They're going to converge at the site that's called pre-autophagosomal structure, or PAS.

Some equivalent structures have been located in mammalian cells as well, but detailed information about the PAS is still unknown.

In my opinion, it's simply some sort of a mini collective consciousness that emerges when the organisms on the mitochondria detect the presence of autophagy in the system. This group is going to converge together and they're basically going to go hunt down some weak cells. That is handsome orc. But what triggers autophagy? Autophagy gets triggered most by nutrient deprivation in yeast, starvation of nitrogen, and other essential factors like carbon, nucleic acid, oxytrophic amino acids, and even sulfate can activate autophagy to some degree. In plant cells, nitrogen and carbon starvation can also trigger autophagy. In mammals, autophagy happens in various tissues in different degrees. There's macro autophagy in the brain, there's muscle autophagy, there's mito autophagy inside the mitochondria, and overall cellular autophagy. So depletion of amino acids is a strong signal for triggering autophagy. But that depends on the type of cell and the amino acids because amino acid metabolism differs among tissues. Some proteins can actually trigger phase two detox pathways in the liver, which inherently are linked to mild autophagy, and amino acids are used in different degrees in different tissues as well. There's a difference between autophagy in the liver and autophagy in the muscles, and you know, vice versa, protein synthesis in the liver and protein synthesis in the muscle cells. So it's all a matter of context. In vivo, it's thought that autophagy is regulated mostly by the endocrine system, particularly by insulin, which is a hormone responsible for shuttling nutrients into cells. Insulin suppresses liver autophagy by raising blood sugar and signaling the presence of nutrients. It's rarely that insulin gets elevated when your body is depleted of energy, and it usually is all most of the time simply high when you have like high blood sugar or you eat and something. Glucagon, which is the counterpart of insulin, releases liver glycogen to be burned for energy, and that increases autophagy. Insulin and glucagon are constantly counterbalancing each other, and most of the time glucagon signals the presence of nutrient deprivation, which is the opposite of insulin. Both amino acids and insulin-like growth factors are regulated by the nutrient signaling of mTOR, or mammalian target of rapamycin. Suppressing TOR with things like rapamycin and CC1779 has been shown to induce autophagy in yeast and other animals. However, not all of the autophagy signaling happens through mTOR, because some amino acid signaling can suppress autophagy independent of mTOR. Even more, recent reports have shown many other factors to be involved in autophagy regulation, such as NFKB, reactive oxygen species, calcium, AMPK and many more. So, what I propose is to look at autophagy not as a binary on and off switch, but more of like a degree dependent state that is mediated through how depleted and deprived the organism is. Because when your body is depleted and deprived of certain nutrients, then it has no other way but to mobilize the backup stores it has stored inside itself. You know, things like liver glycogen, muscle glycogen, ketone bodies, fatty acid tissues, mineral stores in your bones, stem cells, and also the weak cells. Your body is only going to start burning off those weak cells if it feels the need to. You know, if you eat cold at time, then there is simply no reason to be burning off those energy. So yeah, your body has to be depleted in terms of wanting to turn on autophagy and self-destruction.