Autophagy - An amateur guide - Part 1

Disclaimer: I am not a doctor and none of this is medical advice. I am just someone who has a deep enduring interest in improving mine (and hopefully other's) physical, spiritual and mental well being. I research on my own and whatever I learn, I evaluate and implement in my own life to serve as proof that things do get better if we take action. Sunchase.

Can someone tell me about this thing called autophagy?

From what I have seen, heard and read until now, autophagy seems to be a silver bullet for keeping overall good health and diseases at bay. Autophagy, which derives from the Greek words "auto" meaning "self" and "phago" meaning "eating", simply refers to our body's ability to recycle damaged and dead cells/their components.

I'm oversimplifying here, but our cells essentially have two "modes" - "growth mode" or "repair mode". Growth occurs when our body is flush with resources i.e. when we have eaten a meal, here the body uses the nutrients from food to repair damaged cells and grow new ones (apart from performing necessary functions to stay alive). While repair is when the body has an absence of ready nutrients (when we haven't eaten for about 24 hours) and so must tap into its reserves to stay alive (and grow if possible).

Autophagy is the more proper name for this natural repair - wherein the body recycles its damaged/dysfunctional components to make sure we don't die.

If you think about it, it makes intuitive sense for the body to start "eating" less important parts of itself to make sure the more important parts stay alive.

Autophagy has deep evolutionary history/sense behind it: Over the past many millions of years, as food was never plentiful in humanity's hunter gatherer times our bodies evolved to tolerate extended periods of no/limited food. Hence, it was natural for the body to use its stored resources in order to stay alive - and in the process also recycling dysfunctional/damaged components. And though initially characterised as a primordial (really old) degradation pathway (recycling mechanism) induced to protect against starvation, it has now become increasingly clear that autophagy also plays a major role in the homeostasis (optimal health) of non-starved cells.

Biologically, autophagy occurs when a thing within cells called mTOR is turned down. This is considered by cells as a signal to switch on "repair mode". James Clement writes in his book The Switch: "Cells are perpetually carrying out a multitude of chemical reactions needed to keep the cell alive and healthy. This in turn keeps you alive. These chemical reactions share important relationships and are often connected through various pathways. The total reactions that take place inside of a cell are collectively called the cell’s metabolism. The mTOR complex is one such pathway that takes place in nearly every cell. Virtually all health extending and life-span extending interventions that we know of have their effects because of their actions to suppress this switch."

When we eat limited or no food for about 24 hours this mTOR switch will turn down, thus switching the body into "repair mode". And when we have food the mTOR switch will turn up, switching the body into "growth mode". Generally speaking, "repair mode" is more about using body's reserves to stay alive, and "growth mode" is more about, well, growing bigger, become stronger and storing resources for later. 

Our bodies naturally evolved to be more in "repair mode" than "growth mode" - however, with the advent of agriculture some 12000 years ago our lives have slowly become proliferated with easy access to food. We started working large parts of land and storing food for the winter months, for the droughts, for the years of limited crop output etc. This abundance of food meant that more people could have food whenever they felt like it, and so they did. Coming up to the 21st century most of the developed world is used to having meals three times a day with snacking in the middle. what does this mean for autophagy and mTOR? It means that our mTOR switch rarely turns down, so we rarely ever enter autophagy.

So? What is wrong with staying in "growth mode" all the time?

Actually, the answer to this question really depends on your age and lifestyle: if you are below the age of 25 (i.e. young) then there is not much wrong in keeping your body reserves flush with nutrients all the time (esp. the right kind of nutrients, not those from junk food) - Whatever you give your body, it is likely to happily take it and apply to a cause such as adding more muscle mass and growing taller.

The equation really starts changing after we go beyond the 25-30 year old age bracket - By this time our bodies have grown as much as they had to, hence any nutrients over and above those needed to keep you alive (i.e. calories you use through the day) and needed to compensate for repairing injuries are likely to be stored in our bodies (fat, liver and muscles). Again, nothing wrong in storing for the rainy day.

The real problems start when these stores start getting too large and eventually biological debris starts accumulating inside us. Misfolded proteins, pathogens, dysfunctional organelles etc. start piling up inside cells + at an overall body level we additionally have fat that beyond a point starts to have negative health consequences. And this is exactly what happens when we keep on stuffing our bodies with food - we keep our bodies in growth mode all the time. Perpetually being in growth mode leads to the mTOR switch never turning down, so the body never gets a chance to clean out the garbage, and this buildup of junk becomes the cause of diseases like heart disease, diabetes and cancer. That is the problem - both extremes are wrong, we knew starvation was bad, and now know that our abundant lifestyles on the other end of the spectrum have started causing their own problems.

Especially problematic is the quality of the food we have - most of us are having too much sugar, salt, processed foods, simple carbs and so on. For most of our evolutionary history our diets have been seeds, nuts, tubers, whole animals occasionally (esp for their fat) and have not been regimented into 3 meals a day whether we feel hungry or not - So our bodies evolved to adapt to the former. Today the picture is different: we thrive on grains (esp. the highly processed variety), sugary snacks, salty food, lots of meat. Plus we eat whenever we want at the slightest provocation, often reaching for the tastiest snack that has zero nutritional value. So, not only does autophagy never get switched on, even our metabolic health gets messed up alongwith. British medical journal The Lancet conducted a study revealing that 1 of 5 global deaths is a result of unhealthy diets. We are overfed but undernourished - often called affluent malnutrition.

Autophagy vs Ketosis - What's the difference?

That's a great question actually! Ketosis is basically when our bodies start using ketones as a source of energy instead of glucose. Ketones come from the fat in our bodies and you'll know that fat is the real energy reserve in our body. The average person has about 2,500 calories of carbohydrate reserves - stored mostly in liver and muscle - you'll likely run through this reserve in about 24 HOURS. On the other hand an average person has about 130,000 calories stored in fat tissue, which can easily last them WEEKS of no food, that's simply how our bodies evolved to survive when the agricultural and industrial revolutions had not hit us, "starvation" for long periods was a reality (for 99.9% of human history) and our bodies knew how to deal with it using fat reserves.

When the body burns through stored glucose and starts burning fat, the liver produces ketones. The operative phrase here is "burns through", and since we are used to eating multiple carb(y) things, multiple times a day we don't really enter ketosis all that often.

Ketosis in itself has many health benefits too that I have covered here. But for the purpose of out discussion suffice to say that while the pathway to both autophagy and ketosis can appear similar (i.e. fasting), however ketosis can be attained even without fasting and switching to a more fat based diet, while autophagy literally needs you to stop eating. The two however, are potent weapons to increase healthspan when used intelligently together.

So you're telling me fat is good?

Of course it is! Come on, you knew this, your body fat is not the enemy, unless you're carrying more than you need to. We need fat to function—it's an energy bank account that we can withdraw from. The trick, of course, is to make sure we don't let our banks open up branches on every single part of our bodies.

What are the health benefits of autophagy?

Autophagy is essentially a house cleaning mechanism for our cells, hence its benefits also start at the cellular level which then impact the overall body (this list of benefits is from the book The Switch, which I found to be a great guide to understanding autophagy and how to make it work for oneself):

• Recycles damaged proteins, organelles, and other cellular components while defending against misfolded, faulty proteins that can contribute to a number of amyloid-based diseases such as Alzheimer’s. Amyloid is a protein that can abnormally build up in certain tissues in the body
• Provides healthy cells with vital molecular ingredients and energy (through recycling damaged cellular material)
• Regulates the functions of cells’ mitochondria, which help produce energy
• Protects multiple systems in the body to streamline functionality and prevent damage to healthy tissues and organs
• In the nervous system, it encourages the growth of brain and nerve cells—ultimately improving cognitive function, brain structure, and the ability of the brain to rewire and reshape itself through new networks (“neuroplasticity”)
• In the heart, it supports the growth of cardiac cells and protects against heart disease. In the immune system, it helps eliminate potentially harmful pathogens
• Acts as the “guardian of the genome” (this is super amazing because as we grow older our DNA takes damage which then leads to a host of problems). Autophagy protects the stability of DNA and yy chromosomes and potentially preventing illnesses such as cancer and neurodegenerative diseases

Are there any downsides to autophagy?

Of course! Autophagy is essentially you starving your cells to induce something called hormetic stress (basically mild stress that actually makes you stronger). If that hormetic stress then turns into actual full blown stress then there will of course be negative consequences.

Prolonged autophagy can lead to cell death when too many proteins and organelles essential to the cell’s survival are degraded - that is, even after recycling damaged cellular material there is not enough of it around to cater to all the healthy cells in your body. And when enough of your cells die, you will too.

Moderation and striking a balance is KEY, a balance between being in growth and repair mode, too much time in either can be harmful.

There are actually a few ways to properly do autophagy that I have covered in part 2 of this piece.