Lately, a lot of influencers and social media videos have been using the term “Autophagy” as some secret biohack that’s going to cure cancer. It’s your body’s “vacuum cleaner”, eating up all the dead cells, leaving your body fresh.
You often hear about it linked to fasting, giving the impression that it’s unique to not eating food. But that’s not quite true. In fact, autophagy as a whole seems to have been exaggerated in the name of fitness.
This article will go over what autophagy is and its role in your body’s health.
Key Points To Know!
Autophagy is a natural process your body uses to clean up dead cells
Autophagy is always occurring
Various behaviors can increase autophagy, such as fasting, calorie restriction, and exercise
It’s unclear if purposefully maximizing autophagy is beneficial in healthy individuals
Excessive autophagy is a risk associated with maximizing autophagy too much
Most studies on fasting and autophagy have been performed on animals
What Is Autophagy?
Autophagy literally means “self-eating“ and is a cellular degradation and recycling process. It prevents the buildup of defective and dying cell structures, which supports adaptation to stress and ultimately longevity.
It’s how cells clean, repair, and recycle themselves. Here’s what happens
Damaged or unnecessary cellular components (proteins, organelles, etc.) are enclosed in a membrane structure called an autophagosome.
The autophagosome then fuses with a lysosome, which contains enzymes that break down the contents.
The resulting molecules (amino acids, fatty acids, sugars) are reused for energy or rebuilding.
Why Does Autophagy Occur?
Autophagy is essential for cell survival and function and is always occurring on a basal level. It’s the body’s built-in system for cleaning and recycling what’s inside a cell (Chen & Klionsky, 2011)
Recycles damaged cell parts into usable materials.
Removes nonfunctional components that slow cellular performance.
Destroys harmful pathogens like viruses and bacteria that can damage the cell.
Autophagy occurs because that’s how our bodies function. It’s kind of like asking, Why do we breathe?
What Happens If Autophagy Doesn’t Occur?
You would die. Seriously.
Many influencers speak as if autophagy only occurs with Fasting. In reality, autophagy is always running in the background.
This must occur because your cells are continually dying and need to be cleaned up. What’s interesting is that different types of cells have different turnover rates (Chen & Klionsky, 2011)
White blood cells die every 1-3 days
Intestine cells die every 2-5 days
Skin cells every 2-4 weeks
Red blood cells die every 4 months
Liver cells are regenerated every 6-12 months
If autophagy didn’t occur, these old cells would pile up, disrupting normal functions and ultimately leading to your own death.
What Causes Autophagy?
Under normal conditions, autophagy is constantly active at a low level to clear out damaged proteins, defective mitochondria, and other waste. This baseline activity is controlled primarily by the balance of two key cellular pathways (Galluzzi et. al, 2014)
mTOR (mechanistic target of rapamycin): When nutrients are abundant, mTOR activity is high, signaling that energy is available. This suppresses autophagy.
AMPK (AMP-activated protein kinase): When energy levels drop, AMPK activates and inhibits mTOR, allowing autophagy to increase.
As you can see, the abundance of nutrients does play a major role in the level of autophagy. This is why fasting has gained so much interest.
This balance ensures the body only accelerates autophagy when needed during low-energy states, cellular stress, or damage. It’s a core survival mechanism that conserves energy and maintains cellular quality control.
In addition to these two systems, several other mechanisms control the level of autophagy that takes place.
Growth factors: Hormones like insulin and IGF-1 tell the cell that energy and resources are available. They activate the PI3K/Akt pathway, which increases mTOR activity and turns off autophagy, allowing the cell to build new components instead of breaking things down.
Hypoxia: When oxygen is low, the cell activates HIF-1α, which increases autophagy. This helps the cell save energy and clear out damaged mitochondria that waste oxygen.
Tumor suppressors: The p53 protein can either turn autophagy on or off. Under mild stress, it supports autophagy to protect the cell. But if the damage is severe, it can block autophagy and push the cell toward self-destruction (apoptosis).
Can We Increase Autophagy?
While autophagy is always running, many longevity and biohackers claim to be able to increase the rate through fasting. In fact, there are several ways we can theoretically increase rates.
But first, we need to clarify some issues with current studies.
Limited Human Studies Linking Fasting In Humans To Autophagy
Before we go further, it’s important to note that many studies linking fasting to autophagy have occurred in animal studies. While there have been some studies that show an effect in humans, others have shown no effect. (Bensalem et. al, 2025, Chaudhary et. al, 2022)
Further, these behaviors may have a different effect on different tissue cells, i.e., muscle vs. liver.
This DOES NOT mean autophagy isn’t important. It just brings into question whether we should be scheduling our lives around maximizing it.
Fasting
Fasting is generally the most mentioned mechanism we can use to trigger autophagy. As we saw, nutrient availability does play a major role in triggering cellular clean-up.
During Fasting, insulin and glucose levels fall while AMPK rises. This shift inhibits mTOR and triggers autophagy to recycle old cellular components for energy.
Studies show that even short-term fasting of 12-24 hours can measurably increase autophagic activity, particularly in the liver, muscle, and brain (Alirezaei et. al, 2010). However, longer fasts can increase the reaction, with 48 hours seeming to provide a substantial increase.
It’s important to note that the effects of autophagy can differ depending on the specific cells.
Calorie Restriction
If you hate fasting, don’t worry. Calorie restriction also enhances autophagy without needing to fully starve yourself.
It’s challenging to provide a specific number, but generally eating 20–40% fewer calories than maintenance for prolonged durations seems to provide autophagy benefits. Obviously, there is likely going to be an inverse relationship, i.e., smaller deficits require more days.
The mechanism of autophagy through calorie restriction includes;
Reduces oxidative stress
Stabilizes mitochondrial function
Activates longevity pathways like SIRT1 and AMPK
This is one of the main proposed mechanisms linking calorie restriction to lifespan extension in animals and improved metabolic health in humans (Bagherniya et. al, 2018)
Exercise
While most attention on autophagy is given to Fasting and diet, exercise is also a powerful modulator. Research shows that this occurs due to;
Energy imbalance
Oxidative stress
Increased calcium
Protein misfolding (Vainshtein & Hood, 2015)
During training, ATP levels drop and AMPK rises, directly stimulating autophagic pathways. This is especially evident in endurance training and high-intensity exercise, which enhance mitochondrial quality and muscle recovery.
Research suggests autophagy during exercise helps:
Remove damaged mitochondria (mitophagy)
Improve insulin sensitivity
Promote muscle adaptation and resilience
It seems that resistance training and HIIT provide the most benefits, while aerobic exercise still seems to increase its effect.
Nutritional Foods
In addition to diet and exercise, several nutritional compounds are used to induce autophagy
Spermidine (wheat germ, soy, aged cheese)
Resveratrol (grapes, red wine, peanuts)
Urolithin A (a gut-microbiome metabolite from ellagitannins in pomegranate, walnuts, some berries)
When it comes to these foods, frequency and long-term use are more important than having sporadic large feedings. This means if you want to increase autophagy with these, you need to make these foods a regular component in your diet.
Can Autophagy Prevent Disease?
The main interest in autophagy is the claim that it can prevent or even cure disease. This is a highly nuanced subject, as yes, autophagy does prevent disease. Disease prevention and maintaining optimal function are the entire purpose of autophagy.
1. Neurodegenerative diseases: Autophagy clears toxic proteins such as amyloid-β and α-synuclein. Impaired autophagy contributes to Alzheimer’s and Parkinson’s disease (Nixon, 2013).
2. Metabolic disorders: It regulates lipid metabolism and insulin sensitivity. Defective autophagy is linked to fatty liver and insulin resistance (Singh & Cuervo, 2011).
3. Cardiovascular disease: Autophagy removes damaged mitochondria, reduces oxidative stress, and helps maintain cardiac function (Shirakabe et al., 2016).
4. Cancer: Normal autophagy prevents tumor formation by limiting DNA damage and removing malfunctioning organelles, though some cancers later exploit it for survival (White et al., 2015).
5. Aging and inflammation: Autophagy declines with age, leading to cellular debris accumulation and chronic inflammation. Enhancing it through Fasting or exercise slows these processes (Rubinsztein et al., 2011).
So yes, autophagy is a necessary, vital process. However, the real question is whether we should seek to increase autophagy through our behavior.
Is Promoting Autophagy Beneficial?
Just because autophagy is a crucial function that keeps our bodies clean, that doesn’t automatically mean more is better.
The issue is that there is no precise amount of autophagy we should be aiming for. In fact, there’s evidence that the excessive manipulation of autophagy can actually be harmful (Chen & Klionsky, 2011)
So when it comes to whether or not we should be seeking to increase autophagy, it’s hard to say.
What we do know is that autophagy increases by following a healthy lifestyle: lifting weights, staying active, and maintaining a healthy weight. That’s always a good thing.
Does including fasting in that lifestyle provide a beneficial bump? In healthy individuals, more research is needed, but it’s not going to hurt.
Dangers Of Excessive Autophagy
Excessive autophagy, or “autophagic cell death”, occurs when autophagy is engaged too much. Autophagy goes into overdrive, leading to the degradation of essential cellular components and ultimately causing cell death of healthy cells.
The problem is identifying where this line is drawn.
Practical Guidelines To Maximize Autophagy And Health
At the end of the day, it appears you can optimize autophagy by simply following a healthy lifestyle with exercise. With that said, if you’re looking to optimize autophagy healthily, there are several simple guidelines to follow;
1. Perform Fasting or calorie restriction in a cyclical manner
2. Maintain an exercise program that includes HIIT and resistance training
3. Include aerobic exercise in your overall program, as it can maximize exercise effects
When it comes to your nutritional intervention, it’s difficult to identify the best intervention. The best diet for autophagy will ultimately come down to the one that suits your life. Some great options include;
Intermittent Fasting (20:4 or 18:6)- Intermittent Fasting is probably the most accessible diet for most people and is likely all that’s needed. If you’re new to Fasting, start with an 18:6 protocol. However, a 20:4 may provide better results (check out this article where we break down popular IF protocols!)
OMAD (One Meal A Day)- OMAD works well for many people as well. It promotes a long fasting interval, which can maximize autophagy (check out more info here!). Some people do well running OMAD during the week, then eating normally on the weekend.
24-hour Water Fast- For more advanced proponents, following an occasional 24-hour water fast can maximize benefits. Again, this is ONLY for experienced fasters.
Calorie Restriction or Fasting Mimicking Diet- Instead of refraining from food, you can cut your calories for 3-5 days. A fasting mimicking diet is traditionally a 5-day diet in which you consume 1,100 calories on the first day, followed by 800 calories on the remaining days. You could also just cut your calories by 50% for 3-5 days every other week or once a month.
Reference
Alirezaei, M., Kemball, C. C., Flynn, C. T., Wood, M. R., Whitton, J. L., & Kiosses, W. B. (2010). Short-term fasting induces profound neuronal autophagy. Autophagy, 6(6), 702–710. https://doi.org/10.4161/auto.6.6.12376
Bagherniya, M., Butler, A. E., Barreto, G. E., & Sahebkar, A. (2018). The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing research reviews, 47, 183–197. https://doi.org/10.1016/j.arr.2018.08.004
Bensalem, J., Teong, X. T., Hattersley, K. J., Hein, L. K., Fourrier, C., Dang, L. V. P., Singh, S., Liu, K., Wittert, G. A., Hutchison, A. T., Heilbronn, L. K., & Sargeant, T. J. (2025). Intermittent time-restricted eating may increase autophagic flux in humans: an exploratory analysis. The Journal of physiology, 603(10), 3019–3032. https://doi.org/10.1113/JP287938
Chaudhary, R., Liu, B., Bensalem, J., Sargeant, T. J., Page, A. J., Wittert, G. A., Hutchison, A. T., & Heilbronn, L. K. (2022). Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans. Nutrition (Burbank, Los Angeles County, Calif.), 101, 111662. https://doi.org/10.1016/j.nut.2022.111662
Chen, Y., & Klionsky, D. J. (2011). The regulation of autophagy – unanswered questions. Journal of cell science, 124(Pt 2), 161–170. https://doi.org/10.1242/jcs.064576
Deretic, V., & Kroemer, G. (2022). Autophagy in metabolism and quality control: opposing, complementary or interlinked functions?. Autophagy, 18(2), 283–292. https://doi.org/10.1080/15548627.2021.1933742
Galluzzi, L., Pietrocola, F., Levine, B., & Kroemer, G. (2014). Metabolic control of autophagy. Cell, 159(6), 1263–1276. https://doi.org/10.1016/j.cell.2014.11.006
Gao, B., Wang, L., Gong, J., Zhu, Z., Liu, Q., Yuan, H., & Wang, H. (2025). The interplay between physical exercise and autophagy signaling in brain health, neurodegenerative diseases and aging. Frontiers in aging neuroscience, 17, 1579208. https://doi.org/10.3389/fnagi.2025.1579208
Nixon, R. A. (2013). The role of autophagy in neurodegenerative disease. Nature Medicine, 19(8), 983–997. https://doi.org/10.1038/nm.3232
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011). Autophagy and aging. Cell, 146(5), 682–695. https://doi.org/10.1016/j.cell.2011.07.030
Shabkhizan, R., Haiaty, S., Moslehian, M. S., Bazmani, A., Sadeghsoltani, F., Saghaei Bagheri, H., Rahbarghazi, R., & Sakhinia, E. (2023). The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting. Advances in nutrition (Bethesda, Md.), 14(5), 1211–1225. https://doi.org/10.1016/j.advnut.2023.07.006
Vainshtein, A., & Hood, D. A. (2016). The regulation of autophagy during exercise in skeletal muscle. Journal of applied physiology (Bethesda, Md. : 1985), 120(6), 664–673. https://doi.org/10.1152/japplphysiol.00550.2015
White, E., Mehnert, J. M., & Chan, C. S. (2015). Autophagy, metabolism, and cancer. Clinical Cancer Research, 21(22), 5037–5046. https://doi.org/10.1158/1078-0432.CCR-15-0490
