Last Updated on April 12, 2024 by Fasting Planet
Inside your body are trillions of cells, 37.2 trillion, to be exact. Some of these are brand new while other cells are older. Wouldn’t it be neat if your body could remove those older, dangerous cells while boosting your metabolic health at the same time? It can through a process known as autophagy. What exactly is autophagy and when does it begin?
Autophagy is the body’s means of removing dysfunctional or old cells by consuming damaged parts. In doing so, you could turn back the hands of time and possibly avoid the development of diseases. To start autophagy, go on an intermittent fast or try the ketogenic diet, even both.
If you’re interested in autophagy and want to trigger it in yourself but you’re not quite sure where to start, you’re not going to want to miss this comprehensive, in-depth article. In it, we’ll tell you everything you need to know about autophagy and then some, from its benefits, how to do it, when it stops, and how you may start autophagy faster.
Table of Contents
What Is Autophagy?
First, let’s start with the basics, such as a more detailed description of autophagy. This term roughly translates to “self-devouring” from the word autophagos, an Ancient Greek term. Initially described sometime in the 19th century, Christian de Duve–a biochemist from Belgium–was the first to really put the term on the map far later in 1963. During that pivotal year, de Duve discovered lysosome functioning.
Yoshinori Ohsumi received the Nobel Prize in Physiology or Medicine 2016 for his discoveries of mechanisms for autophagy.
As we touched on in the intro, your body has no shortage of cells at any given time. Their lifespan depends on the cell. For example, white blood cells will only stick around in the body for just shy of two weeks while liver cells can last for more than a year. Red blood cells have long lives, too, roughly 120 days. Even your skin cells on the top layer are there for about a month before sloughing off.
The longer any of these cells are in the body, the more damaged they can become. Age can also make cells less efficient than they once were. If these older cells are damaged but still within the body, it’s believed you may impact your lifespan, shortening it.
That’s why our bodies are conditioned to perform autophagy. Breaking the word down, “auto” refers to self, or our own bodies, and “phagy” is another word for eat. In other words, our cells eat themselves.
Now, the cells can discern which ones are healthy and which aren’t, so they only take the damaged parts. If the whole cell is bad, that cell may be consumed in its entirety. Should only certain parts be affected, these parts will be removed.
Source: novusbio.com
Autophagy is referred to as a mechanism for self-preservation, and it may have evolved over the generations to keep humans alive. That said, we people aren’t the only ones who can perform autophagy, by the way, but fungi, plants, and animals do it as well.
The Types of Autophagy
There are generally three recognized types of autophagy. These are chaperone-mediated autophagy or CMA, microautophagy, and macroautophagy. Let’s talk more about each these now.
- Chaperone-Mediated Autophagy: CMA involves lysosomes, a type of organelle that’s membrane-bound. Soluble cytosolic proteins are chosen in a chaperone-dependent fashion. These are then bonded to the lysosomes and moved through the lysosome’s membrane. In doing so, the cytosolic proteins begin to break down, causing autophagy in this fashion.
- Microautophagy: A type of mediated autophagy, microautophagy relies on cytoplasmic material. Cytoplasm is a cell’s inner material that’s sealed off by the membrane of the cell, save for the nucleus. This cytoplasmic material gets caught within the vacuole (in fungi and plants only) or the lysosome (in mammals), creating a pathway in which cells that are starved or lack nitrogen can still live.
- Macroautophagy: Macroautophagy is related to microautophagy in that vacuoles, lysosomes, and cytoplasmic materials all play a role. This time, the vacuoles or lysosomes will break down the cytoplasmic materials and then recycle them. Autophagosomes, a type of structure with two membranes, then attach to the lysosomes.
What Are the Benefits of Autophagy?
Although it sounds a little gruesome, autophagy is a natural, even beneficial bodily process. Still not convinced? Here are some of the many perks you can enjoy once you harness the power of autophagy.
Reduce the Rate of Cell Death
Apoptosis is a multicellular organism cell death that’s programmed to occur. Before the cell dies, it may undergo global mNRA decay, fragmentation of chromosomal DNA, chromatin condensation, nuclear fragmentation, shrinkage, and blebbing. A bleb is another word for a plasma membrane bulge or abscess.
When a cell dies, it doesn’t go quietly nor cleanly. That leaves a lot of mess for your cells to mop up, which takes both time and energy. Through autophagy, damaged cells get eaten and recycled before they reach the point of apoptosis. Not only does this prevent the need for cleanups, but it allows your cells to conserve their energy and use it more wisely, such as in the creation of fresh cells.
Boost Your Heart Health
Research in a 2018 study published in Science Translational Magazine and a few other related studies all point out a connection between autophagy and a healthier heart. It’s believed that the cell recycling can extend to even your heart, cleaning out the organelles and proteins there that are old and damaged.
This may lessen or even eliminate your chances of developing cardiovascular disease and heart disease.
Improve Metabolic Efficiency
If you want to lose weight, you need a metabolism that works especially well. It turns out autophagy can help with this, too.
Your body contains mitochondria, a type of cell that makes energy for fat burning. Should the mitochondria become toxic, which can happen naturally, then your cells are at risk. When autophagy occurs, any toxic mitochondria are consumed, sparing your cells and keeping your metabolism working well without any disruptions.
It goes even further than that. If damage has affected the cells that make protein packages for energy, this can hinder your weight loss goals as well. Through autophagy, your body can repair or replace these important cells. Now your goals of losing weight are never derailed.
There will also be fewer toxins floating around in your system, as autophagy promotes toxin excretion, too. Your fat cells won’t keep these toxins, either, so they move out of the system.
Further, with less inflammation (something we’ll talk about shortly), you don’t hold as much weight. That’s because bodily swelling triggers insulin production, and insulin can cause you to store excess weight.
Finally, when your body actively begins autophagy, it uses fat for energy instead of proteins. The only exception is if you’re on an intermittent fast for a long period, in which case proteins may be used as well.
This is something we discussed in our most recent blog post. Proteins, especially muscle proteins, are necessary for muscle mass. The problem becomes some intermittent fasts can deprive you of this muscle mass. While the expectation is your body will torch body fat after burning through its glucose (energy) supply, when protein is burned in conjunction with fat or on its own, your muscles can shrink.
If you can prevent that in any way, you’re certainly going to want to.
Possibly Ward off Cancers and Other Diseases
Damaged DNA, instability of genomes, and long-term inflammation can all potentially lead to a higher risk of cancer. Through autophagy, your cells are healthier and more stable, which can contribute to avoiding cancer.
That said, if you already have cancer, autophagy can hurt way more than it helps. According to a 2018 study in the International Journal of Molecular Sciences, cancer patients have experienced a different type of phenomenon.
Their cancer cells may have a longer life if autophagy continues. While autophagy will trigger damaged cells, it doesn’t discriminate which “healthy” cells it helps, even if those happen to be cancer cells. This can help cancer spread in some cases. At the very least, the cancer is around longer, neither of which is good.
Help Your Skin Look Healthier
Fresher, brighter skin is a goal on everyone’s self-care list, but it’s not as always as easy to achieve it as it seems. As our cells withstand physical damage, humidity, temperature changes, air pollution, and chemicals, this can cause a buildup of toxins in our skin. All this damage leaves us look older than our years might otherwise suggest.
The fresher our cells, the more youthful our visage. When our skin cells are renewed, we may even have glowing skin.
Enhance Your Brain Health
Like autophagy is immensely beneficial for your heart, the same is true of your brain. The cells here can get overrun with toxic proteins known as amyloid-tau and amyloid-beta. Both these proteins may be responsible for the development of Alzheimer’s disease.
Further, if too many of these dangerous proteins build up in your body, then your chances of getting dementia can go up. Not only that, but you’re at risk of Huntington’s and Parkinson’s as well.
Progress Digestive System Health
Your gastrointestinal tract has cells on either side that promote digestion. Well, if they’re fresh enough, that is. As these gastro cells age or are damaged, your chances of having a gut immune response increase. This can become chronic without medical intervention, leading to inflamed bowels and other uncomfortable symptoms.
Autophagy–especially when done in conjunction with an overnight intermittent fast–will keep your digestive system performing well.
Aide in Muscle Performance
Do you exercise a lot? Then you’re surely aware of the muscle pain that comes from trying new things at the gym. This pain is the result of inflammation and microtears in the muscle tissue. That’s why it’s always advised you take a rest day afterwards so your muscles can heal and fix themselves in time for your next workout.
Autophagy of the muscle cells will heal these tears and other damage. More than that, you also need less energy for future muscle use, and your energy balance increases so you may not hurt your muscles so easily in the future.
Lessen Rates of Infectious Diseases
Besides lowering your cancer risk with autophagy (well, potentially) and your chances of getting Alzheimer’s and related diseases, there are yet more infectious diseases you could avoid through cell recycling. These include tuberculosis, HIV, and other virus-causing illnesses.
Why is that? Autophagy can activate our immune system, bolstering it so it can fight off foreign invaders better. Also, viral and bacterial microbes within a cell may be consumed through autophagy, keeping you healthier.
Reduced Bodily Inflammation
We’ve already discussed inflammation and how it can play a role in the quest for a trimmer body. While some inflammation is okay and even quite normal, such as to get your immune system to fight off illness-causing bacteria, for the most part, you don’t want your body swelling unnecessarily.
Through autophagy, you can either increase or decrease inflammation, but it’s always to the point where it’s just right. If your body needs inflammation to use as a warning bell to your immune system, autophagy will increase swelling. If you need less, then by erasing antigens, your body controls its swelling. That’s because antigens are a type of protein that send inflammation signals to the rest of your body.
Lengthen Lifespan
In 2018, Molecules and Cells published an interesting study on autophagy in animals. After inducing autophagy through resveratrol supplements, genetic engineering, and fasting, the animals undergoing autophagy were said to live longer.
Further, when the animals had fewer genes that triggered autophagy, even resveratrol and intermittent fasting couldn’t boost their lifespan.
It’s very much believed the same benefits could expand to us people, too.
How to Induce Autophagy?
By now, you understand more about autophagy, including how it works and its benefits. If you wanted to trigger this cell renewal process in yourself, how and where would you begin? When does autophagy start, anyway?
Autophagy happens when we deprive our body of calories. One way to do that that’s been a frequent topic of discussion on this blog is intermittent fasting. If you’ve missed those posts, intermittent fasting is an on-off fasting cycle.
For instance, you might eat for 24 hours and then fast for the next 24 hours, which is known as alternate-day fasting. You could eat eight hours of every single day but then spend the next 16 hours fasting, as this is called the 16:8 method. You may even limit yourself to only 500 or 600 daily calories, which is the 5:2 diet. This means you ingest up to 25 percent of the daily recommended caloric limit.
Intermittent fasting is a great aide for meeting weight loss goals, and it may promote a longer life in warding off heart disease, diabetes, and obesity. Longer periods without food also affect our cells for the better.
When our bodies have fewer calories coming in, our internal responses begin to change. Our system has no idea we’re on an intermittent fast and not starving to death, so the body goes into famine mode.
When does autophagy kick in? When we’re in this famine mode. According to a 2010 study in the journal Autophagy, when mice were on 24-hour supervised fasts, their bodies began producing more autophagosomes.
As we talked about in the section on the types of autophagy, autophagosomes are vesicles with two membrane layers. As autophagy gets underway, the cellular material within the autophagosomes breaks down, leading to the creation of a phagophore, also known as an isolation membrane. This develops close to the autophagic cargo. The phagophore will grow to the size necessary to envelop the autophagic cargo.
In other, simpler words, an autophagosome is like a little indicator that yes, your body has entered autophagy and those old cells are being phased out and/or recycled.
Does this study mean it takes only 24 hours to enter autophagy as humans? For some of us, yes, but not all. Also, you have to keep in mind that while lab mice make good test subjects, we are not mice and vice-versa.
Some experts believe we might not even have to wait as long as mice to begin autophagy, in that we people could do it in as few as 18 hours, even 20 hours of intermittent fasting. Others say it can take days, such as two or three, before autophagy really begins doing its thing. It really depends.
If you’re new to fasting, a 72-hour fast may be too daunting, and that’s fair. In your case, it’s better to start with a shorter fast and keep extending the length. Seasoned fasters who are up to the challenge may engage in a multi-day fast to clean up those old cells and make room for new ones.
It turns out you don’t have to fast super often to enjoy autophagy. Even if you go on an intermittent fast several times a year, your cells should be in good shape. That said, if you enjoy your first intermittent fast and this is something you want to keep up with, that’s a good idea as well. It just means your cells will be in their best shape.
In fact, a JAMA Oncology report from 2016 involving cancer risk shows why intermittent fasting for autophagy is so worthwhile. The group of women who participated in the study, all with breast cancer, began a form of intermittent fasting. Those who fasted longest daily, such as 13 hours or more, also noticed their breast cancer returned more seldomly compared to the women who didn’t fast.
Okay, so how would you know your body has started autophagy anyway? Sure, you’re producing more autophagosomes, but will you feel different? Currently, the only way to tell is to track your autophagic flux, which reviews protein ratios as these fluctuate throughout the day. This is, as you may imagine, complicated work.
In fact, it’s so hard to track whether you’re in autophagy that a 2017 study published in the International Journal of Molecular Sciences stated that “it’s practically impossible to monitor autophagy properly in humans.”
That doesn’t mean you can’t try, though. A ketone meter can be one such tool you rely on. This meter measures your ketone bodies.
If you’re not familiar, ketone bodies are molecules within a ketone group. They come from fatty acids in the liver and are produced in greater quantities during diets and fasting.
Knowing your glucose levels is also another good indicator that autophagy may working.
Glucose comes from the foods we eat and is a primary energy source for the body. When we deprive ourselves of food, the body has no new glucose to use. Instead, it must dig into its energy stores and burn through all these. From there, it may use fat and proteins from muscle mass for energy instead, as we talked about earlier.
If you’re making more ketone bodies and have lower glucose levels, then you can rightly assume your cells are in autophagy. That’s about the only way to be certain outside of getting your hands on an autophagic flux.
When Does Autophagy Peak?
The peak of autophagy is a desirable state to be in because it means your body is most effectively eating and clearing away defective cell parts. Like Rome wasn’t built in a day though, you don’t automatically enter autophagy at peak efficiency. It will take time to reach that point, but how long exactly?
The answer varies, but for some people, autophagy may peak in as little as 24 hours. For others, it’s 48 hours, and for other fasters still, it may be more than two days.
The ambiguity in this answer is present for the same reason it’s hard to say how long it will take your body to begin burning fat instead of glucose during an intermittent fast.
In that situation, there are all sorts of factors present that make it different for everybody. What did you eat before the fast? What does your diet usually look like? Have you ever fasted before? How long will you fast now? If you were to have excess glucose reserves, then it may take longer for your body to burn fat than someone who has little glucose.
Two protein kinases signal autophagy. These are AMP-activated protein kinase or AMPK and the mammalian target of rapamycin or mTOR. AMPK acts as a type of catabolic switch. You can turn that switch on, so to speak, in all sorts of ways. These include reducing calories, exposing your body to cold, eating low-carb, exercising, and intermittent fasting.
When the switch is on, autophagy is more likely to occur.
mTOR is also like a switch for the body, this time one that promotes growth. That said, this growth does not always refer to autophagy positively. In fact, too much mTOR can interrupt autophagy or slow it down. If you consume excess calories, your body has many amino acids or glucose, or your insulin supply gets too high, the mTOR switch is on.
Thus, by cutting calories more and eating less, like during an intermittent fast, your body tells the AMPK switch to stay on and turns off the mTOR switch. That’s part of why it’s so important you fuel your body the right way before beginning an intermittent fast, which we’ll discuss a little later in this guide.
Can You Speed up Autophagy? How?
If you’re relatively new to intermittent fasting, the thought of going several days in a row without food can be daunting. We again don’t recommend new fasters jump right into a multi-day fast, so how can you make autophagy happen faster? Is it possible? How would you do it?
Your diet is the key to how quickly your cells will enter autophagy. As we said in the last section, what you eat can either turn on the mTOR switch–which slows and even stops autophagy–or the AMPK switch, which leads to autophagy. High-carb, fatty, unhealthy foods in high quantities are to be avoided. Instead, a ketogenic diet may promote faster autophagy.
For protein, you want to eat such foods as cottage or ricotta cheese, plain Greek yogurt, natural cheeses, eggs, lamb, and pork. Seafood like shrimp, tuna, sardines, and salmon is good, too. You can also eat beef, venison, turkey, and chicken, although it’s preferable the latter two are dark meat if you can.
You can get your keto fats from nut butters (without sugar), nuts, coconuts, hemp hearts, avocados and their oil, and olives and their oil. Seeds are also a great source of fat, among them sesame seeds, pumpkin seeds, chia seeds, and flaxseeds.
Stick to veggies like Brussels sprouts, celery, zucchini, kale, and bell peppers to get into keto. Cucumber, green beans, spinach, and cauliflower are also okay.
Here’s a list of foods that could slow down your keto diet and thus limit autophagy:
- Sweetened cocktails, beer, wine, and most other alcohol
- Hydrogenated fats and trans fats, including margarine
- Peas, potatoes, corn, and other vegetables with high starch content
- Fruit, with the exception of berries (in smaller quantities), tomatoes, limes, and lemons
- Crackers, pretzels, chips, and most snack foods
- Soda, juice, and any other high-sugar drinks
- Sweeteners and added sugars
- Low-fat dairy
Here are some other things to try that, while maybe not as effective, could help your body enter into autophagy sooner.
Get Your Zzzs (sleep)
You don’t have to worry about your body halting autophagy just because you’re not awake, as that won’t happen. This cell-renewing process will continue while you snooze, but the quality of sleep you get is important here.
When rodents were tested for autophagy during sleep in a 2016 Chronobiology International study, the researchers found that interrupted sleep may impact autophagy. That’s because this bodily process seems to match our circadian rhythms. Thus, when these rhythms get disrupted, so too does autophagy.
Prioritize Fitness
Although exercising might be the last thing you want to do while on an intermittent fast, it’s worth your while to try. A 2018 report in the journal Nature had 12 male participants who all exercised for autophagy. Each man participated in the study for eight weeks, exercising thrice weekly. These exercises would consist of either interval training at a high intensity or state cycling for a determined period.
Neither exercise was better for triggering autophagy, so any bodily movement works.
Try a Protein Fast
If you think you’ll go on an intermittent fast for autophagy in the next few weeks, then do a protein fast now. Twice weekly, eat no more than 25 grams of protein. The next day, your system will begin breaking down and recycling those proteins, lessening inflammation and preserving muscle mass.
How to Fast for Autophagy
To recap, if you’re still wondering how long to fast for autophagy to occur, that can be anywhere from 24 hours to more than 48 hours for some. By choosing a fasting type that suits you and treating your body well during the fast, you may find your system more successfully clears out old cells.
Here’s what to do when fasting for autophagy in a step-by-step format.
Step 1: Choose the Type of Fast You Want to Do
Before you start anything, you must decide which type of intermittent fast is ideal for you. We’ve already covered alternate-day, 16:8, and 5:2 fasting types. Another popular type among intermittent fasters is the water fast.
On a water fast, you’re permitted to only consume water. On a soft water fast, you can bathe or shower, brush your teeth, and wash your hands with water. Hard water fasts prohibit all that.
As you choose a type of fast, ask yourself which would be easiest for you to do longer. For some, water fasts are good because drinking water can make you feel full, which lessens hunger pangs. Others may prefer a 5:2 or 16:8 fast where some food is allowed.
Step 2: See Your Doctor
Once you know the fast you want to start with, schedule an appointment with your doctor. This is just a customary checkup to ensure you’re in optimal health for fasting. If your doctor finds any underlying health conditions that may make intermittent fasting difficult, you have two options. You can either skip fasting for now or you can do a medically-supervised fast in which your doctor would have much more involvement.
Step 3: Prepare Your Diet
You’ll soon wind down your food consumption to very little or perhaps nothing at all. As we’ve explained already, what you feed your body in the days leading up to your intermittent fast is crucial. The ketogenic food examples we listed before are all healthy, balanced choices that will put your body in a great frame for beginning autophagy on your fast.
Step 4: Exercise During the Fast
Exercise can maintain your muscle mass, which your body may try to burn during an intermittent fast, and it keeps your body in autophagy as well. Like that Nature study proved, any type of exercise works, so if you don’t have a lot of energy, try yoga or other lighter exercises. Even a walk or jog around the neighborhood suffices. Any movement is better than none at all.
Step 5: Get Plenty of Sleep
It’s not necessarily easy to sleep when your stomach is grumbling. The good news is that the longer you fast, the better your sleep becomes.
A study from 2016 in Cell Metabolism notes how our circadian clocks are soon fortified through time-restricted eating, a type of intermittent fasting. When our circadian clock is at its best, we fall asleep quickly, don’t wake up as much in the night (if at all), and actually feel rested the next morning.
Step 6: Reintroduce Your Diet After the Fast
The fasting window has closed, which means your intermittent fast is over. Switching gears right back to the foods you were eating before the fast can be too much on the system. You do want to begin eating every few hours, but in small quantities. If you prefer your foods in liquid form for that first day or so, that’s normal.
What Stops Autophagy?
As you recall, autophagy can be quickly halted by mTOR, a kinase that triggers feedback loops that can slow the death of a cell. By eating too many calories, that mTOR switch is turned on. A ketogenic should keep your caloric load under control, as can intermittent fasts such as the 5:2 or 16:8 method.
Too much insulin can also trigger mTOR. Referred to as our body’s primary anabolic hormone, insulin comes from the pancreas. When insulin levels get consistently high, it’s possible to develop hyperinsulinemia. This condition has a connection to cancer, heart disease, and obesity.
Insulin is directly related to glucose as well. Your blood sugar or glucose is converted via insulin. You can then use that glucose for energy. When your blood sugar increases excessively, you may develop hyperglycemia, which is common in diabetics. It just so happens that high glucose can also affect autophagy thanks to mTOR.
Autophagy and coffee
We also have to talk about coffee. Some people believe that coffee can have a negative impact on autophagy, slowing or stopping it. This is mostly due to the primary ingredient in coffee, caffeine.
Is caffeine a friend or foe to autophagy? Let’s see what the studies had to say.
In 2017, the Canadian Journal of Physiology and Pharmacology did a study on 10 adult participants. They consumed caffeine every morning during breakfast. The researchers found that ketone production actually increased thanks to the caffeine, as did plasma-free fatty acids. Granted, even the study notes that “whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.”
Another study, this one a 2014 report in the journal Biochemical and Biophysical Research Communications, looked into how caffeine influenced autophagy in rats. The autophagy, which was described as “AMPK-dependent,” did increase thanks to the caffeine and was seemingly due to the skeletal muscles’ pathways.
So far, so good, right? Yet a 2016 study in the Nutritional Journal noted how coffee can both lower your tolerance to glucose and your sensitivity to insulin in the short-term, but not the long-term. In fact, it’s believed you may even be able to ward off type 2 diabetes if you’re a regular coffee drinker.
The research is clear that coffee isn’t as detrimental for cell renewal as some people may believe. If you’re allowed to have coffee on your intermittent fast, go for it. It won’t limit AMPK, so autophagy should not be negatively affected.
Conclusion
Autophagy is the body’s process of removing old cells by consuming or recycling them. These damaged cells increase our risk for disease, so by getting rid of them, we may be healthier and even lead longer lives.
Autophagy begins when we restrict calories, either through a ketogenic diet or an intermittent fast. It can take upwards of two days, sometimes longer, for autophagy to reach its peak, but this is different from person to person.
If you’re fasting for ketosis, it’s important to maintain sleep and get exercise as well, as both can help your cells eat more of the bad stuff and keep the good. Best of luck!