Autophagy is how our cells recycle their components. Most of the time it runs quietly in the background. But when cells are stressed (such as during fasting or in the presence of dysfunctional proteins) it is increased in order to protect us. Read on to learn about autophagy, its definition and how it works, autophagy regulation, and how to increase autophagy through things like fasting.
Learn how you can maximize autophagy for your own health benefit.
What is Autophagy?
Autophagy (from the Greek for self-eating) is the regulated process by which a cell degrades its dysfunctional or foreign components. The cell can then recycle useful chemical components for further purposes .
This allows autophagy to regulate the balance of protein composition in a cell, prevent the buildup of toxic waste products, maintain cellular organelle function, remove invading pathogens, and help sustain cells during periods of starvation .
The scientific importance of understanding autophagy was highlighted when the 2016 Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy.
Mechanism of Autophagy
Essentially, autophagy is the creation of a ‘garbage bag’ (autophagosome) that collects cellular components and then takes them to the cell’s ‘recycling center’ (lysosome) to be broken down into their parts which can then be recycled into new components.
Autophagy-related genes (ATG) are responsible for creating the structures that carry out autophagy. The VPS34 complex initiates the autophagosome, ATG9 contributes to its expansion, and the ATG12-ATG5–ATG16L1 complex recruits ATG8 proteins which complete formation and are involved in targeted capture .
Other genes are involved in turning autophagy on and off. In particular, genes that can detect changes in the cell. mTOR responds to the level of nutrients in a cell and decreases autophagy (by disrupting ULK1 preventing the formation of the VPS34 complex) when there are plenty of nutrients available. AMPK monitors the energy levels in a cell (the amount of ATP) and activates autophagy when they are low. HIF1A detects oxygen levels and turns on autophagy (targeting mitochondria) when they are low (hypoxia) [4, 5].
The Benefits of Autophagy
When things are running smoothly in a cell, autophagy occurs at a low level, helping to recycle worn-out cellular components. It’s a type of ‘maintenance’ mode.
But when things become stressed in a cell (not enough nutrients or energy, dysfunctional components, or invasion by microbes), autophagy is turned up in order to help protect us. A ‘stress response’ mode.
Activation of autophagy counteracts the age-associated accumulation of damaged cellular components and enhances the metabolic efficiency of cells .
Autophagy is a response to stress that helps cells to become more resilient and conservative with their energy.
These processes are reported to extend the lifespan of several species .
Protects Against Psychiatric Disorders
Typical functioning of autophagy provides protection against the development of psychiatric disorders. Disruptions to autophagic processes have been associated with increased risk for some psychiatric conditions .
Prevents Neurodegenerative Disorders
Many neurodegenerative disorders stem from the accumulation of deformed proteins in and around neurons, inducing gradual brain cell death and subsequent loss of mental faculties .
Autophagy protects us by removing these proteins.
In Huntington’s disease it removes the huntingtin (HTT) protein , in Alzheimer’s disease it removes amyloid ꞵ (created from the APP protein) , in Parkinson’s disease it removes ⍺-synuclein (SNCA), and in dementia it removes microtubule-associated protein tau (MAPT) .
Helps Fight Against Infectious Diseases
Autophagy contributes to fighting infectious diseases in three ways; 
- Direct removal of microbes from inside of cells (xenophagy)
- Removal of toxins created by infections
- Modulation of the immune response to infections
Helps to Regulate Inflammation
Autophagy can both increase and decrease inflammation responses within the body.
It increases inflammation by presenting evidence of pathogen invasion and turning on the immune response.
Autophagy then decreases the inflammation brought about by an immune response by clearing the cell of antigens that are stimulating the response. Additionally, autophagy also removes pro-immune response molecules produced by the cell in response to an invasion .
Improves Muscle Performance
When exercising we place stress on our cells. Energy use goes up and components get worn out faster.
Autophagy is increased in response to this in order to: 
- maintain energy use balance within the cell
- reduce the amount of external energy required (by more efficiently recycling existing energy molecules)
- ensure that degraded cellular components are removed before they begin to cause any trouble
Involved in Cancer Prevention
Autophagy plays a role in preventing the onset of cancer and inhibiting the growth of early-stage cancers.
Autophagy suppresses pro-cancer processes such as chronic inflammation, DNA damage response, and genome instability .
Mice genetically engineered to have impaired autophagy are reported to have increased rates of cancer .
Unfortunately, the protective roles of autophagy may also be harnessed by cancerous cells within tumors.
Cons of Autophagy
Can Support Tumor Growth
While autophagy is useful for preventing the onset of cancer it can later be used by advanced cancerous cells. As tumors grow the cells in the middle become isolated from the blood supply and begin to undergo nutrient and energy stress. Activation of autophagy can provide support to these cancerous cells .
How You Can Increase Autophagy
Autophagy is an essential cellular process that can be activated in order to provide benefits to the body and mind.
There are basically two options; you can induce a bit of stress on your body to activate autophagy or you can ingest something that turns it on.
Stressing the body:
Artificially turning on autophagy:
- Herbal remedies
- Traditional Chinese Medicine constituents
- Cancer therapy drugs
Lifestyle Choices That Can Increase Autophagy
1) Aerobic Exercise
Not only does exercising make you feel great and increase your fitness, but it also activates autophagy to ensure your cells fully recover from the process.
The benefits of increased autophagy can thus be harnessed through exercising.
For example, the observation that aerobic exercise activates autophagy in the brain suggests that going for a run may help with protecting against the onset of neurodegenerative disorders by clearing out any malformed proteins in your neurons.
2) Intermittent Fasting and Caloric Restriction
A lack of nutrient influx activates autophagy to increase the recycling of cellular components, ensuring cells continue to properly function with less requirement from external resources.
This can be achieved either by going for a period without any food (fasting) or by reducing the amount of food you eat (caloric restriction).
Short-term fasting has been demonstrated to induce profound neuronal autophagy and may be a good method for combating neurological conditions .
3) Promoted by the Ketogenic Diet
The ketogenic diet reduces carbohydrate intake and increases fat intake resulting in a shift of energy use from glucose to ketones.
This shift mimics the process that occurs during fasting and can lead to an increase of autophagy .
Ketogenic diets are reported to be particularly effective at promoting autophagy in the brain .
The ketogenic diet is a good alternative for individuals who struggle with fasting or caloric restriction approaches.
4) Sleep is Vital
Autophagy can occur during sleep. The circadian rhythm not only helps control your sleep cycle, but it is also linked to autophagy. Our biological clock affects the autophagy rhythm. Getting a proper amount of sleep will help with autophagy .
In mice, sleep interruptions negatively affected autophagy. Sleep disruption caused autophagy protein transmission to be interrupted .
Foods that Boost Autophagy
5) Induced by Coffee
The health benefits of coffee have provided some contrasting results. With some studies reporting chronic consumption reducing overall mortality while others suggest coffee may increase inflammation.
6) Increased by Green Tea
7) Stimulated by Coconut Oil
For more information on how coconut oil can add to your health check out this post.
8) Can be Activated by Ginger
It is reported to block mTOR which in turn activates autophagy.
9) Increased by Galangal
Galangal rhizomes are used in traditional Southeast Asian dishes.
10) Activated by Extracts of the Reishi Mushroom
Natural Supplements that Increase Autophagy
11) Activated by Resveratrol
In order to ingest similar dosage levels to those in the reports, it may be necessary to use resveratrol supplements.
The interaction between resveratrol and sirtuin genes is thought to facilitate the long-life benefits observed in some species.
12) Turned Up by Medium-chain Triglycerides (MCTs)
MCTs can be purchased in an oil form.
13) Increased by Curcumin
14) Autophagy is Activated by Vitamin D
Research has shown that vitamin D induces autophagy and potentially plays a role in protecting pancreatic β‑cells, providing a possible avenue for diabetes therapeutics .
15) Promoted by Omega 6 and 3 Polyunsaturated Fats
A study showed that the inclusion of omega 6 polyunsaturated fatty acids in the diet of C. elegans significantly increased their lifespan .
An excellent source of omega fatty acids is fish oil. Read this post for more ways that fish oil can keep you healthy.
16) Increased by Nicotinamide
It has been reported to forestall Alzheimer’s through increasing autophagy in neurons .
In particular, its ability to induce autophagic recycling of mitochondria is beneficial to cellular health .
For more information about where to find nicotinamide supplements and further health benefits check out this post on Nicotinamide Riboside.
17) Autophagy is Activated by Melatonin
18) Enhanced by Ginseng
These activities are suggested to produce anti-cancer effects .
19) Increased by Lithium
Lithium is a chemical element that is reported to have many health benefits when used as a supplement.
IP3 is important to cellular Ca2+ transport and plays a role in neuronal plasticity.
Lithium has been reported to enhance degradation of aggregate-prone proteins that cause Huntington’s disease, Alzheimer’s, and dementia .
20) Autophagy is Boosted by Spermidine
Spermidine is a polyamine compound found in a wide range of foods .
It has been reported to assist with age-related declines and prolong the lifespan of several organisms through the activation of autophagy .
Foods with the highest reported levels of spermidine are soybean (dried) and one-year-old cheddar cheese .
21) Induced by Sulforaphane
22) Promoted by Trehalose
Trehalose is a sugar that contributes to protecting the body.
23) Induced by Ursolic Acid
Ursolic acid is a substance that comes from a variety of plants and herbs. It has been reported to have a variety of health benefits.
Ursolic acid has been shown to increase autophagy and contribute to cell death of breast cancer cells .
24) Other Natural Supplements that Increase Autophagy
- Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein via mTOR pathway .
- Cedrol, found in the essential oil of conifers, induces autophagy and cell death of lung carcinoma cells .
- Amla extract from Indian gooseberry (Emblica officinalis) induces autophagy and inhibits ovarian cancer proliferation .
- Black hoof mushroom (Phellinus linteus) extract induces autophagy and inhibits breast cancer cell growth .
- Extract of European black nightshade (Solanum nigrum) induces autophagy and inhibits colorectal carcinoma cells .
- East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes .
- Neferine from the Indian Lotus (Nelumbo nucifera) induces autophagy through the inhibition of PI3K/Akt/mTOR pathway .
- Anacardic acids, found in the shell of the cashew nut (Anacardium occidentale), induce autophagy and inhibit lung carcinoma (A549) cells .
- Naringin, found in citrus fruits (especially grapefruit), induces autophagy-mediated growth inhibition of cancer cells .
- Astin B, from Aster tataricus, induces apoptosis and autophagy in liver cells 
- Oridonin, purified from the herb Rabdosia rubescens, induces autophagy and cell death in prostate cancer cells .
Drugs that Activate Autophagy
25) 6 Drugs that Increase Autophagy
Some drugs target the autophagic pathway in order to create a beneficial effect.
They can increase autophagy to help clear troublesome targets (e.g. bacteria and dysfunctional proteins) from within cells or they can use autophagy as a means of inducing the death of cancer cells.
Always consult a physician before taking any medication.
- Sirolimus, also known as rapamycin, induces autophagy by inhibiting mTOR .
- Fentanyl is a potent, synthetic opioid pain medication that induces autophagy via activation of the ROS/MAPK pathway .
- Carbamazepine, a medication used primarily for the treatment of epilepsy and neuropathic pain, induces autophagy and has been shown to act on multidrug-resistant Mycobacterium tuberculosis .
- Metformin, a diabetes drug, is an autophagic promoter that has been trialed in Alzheimer’s treatment and reported to improve anxiety-like behaviors [80, 81].
- Imatinib, a chemotherapy medication used to treat cancer, induces autophagy in chronic leukemia cells .
- Bortezomib, an anticancer drug, induces autophagy in head and neck carcinoma cells .
How to Decrease Autophagy
While eating lots of protein and not exercising will prevent extra activation of autophagy it won’t actively decrease the basal level of autophagy in cells either.
5 Supplements that Decrease Autophagy
- Eugenol, a phenolic acid found in clove (Syzygium aromaticum), was identified from a screen of 86 traditional Chinese medicines to have the strongest ability to decrease autophagy .
- Bafilomycin A1, a macrolide antibiotic derived from Streptomyces griseus, has been reported to inhibit autophagy .
- Elaiophylin was identified from a screen of North China Pharmaceutical Group Corporation’s pure compound library of microbial origin to have the best ability to decrease autophagy .
- Oblongifolin C, a phenolic acid from the Asian tree Garcinia yunnanensis, inhibits autophagy and has been described as having anticancer properties .
- Matrine, an alkaloid found in plants from the Sophora genus, is reported to be an autophagy inhibitor (via modulation of the lysosomal process) .
6 Drugs that Decrease Autophagy
The Genetics of Autophagy
Autophagy is tightly controlled by turning on and off autophagy-related genes (Atg). Individual genetic differences can strongly influence this process.
Go to SelfDecode to learn how you can have your own genetic makeup analyzed for autophagy-related conditions.
Genes Involved in the Mechanism of Autophagy
Autophagy begins with the creation of a phagophore from membranes enriched with phosphatidylinositol 3-phosphate (PI3P) .
Expansion of this membrane region is facilitated by ATG9 which cyclically introduces more lipids to the bi-lipid membrane .
The phagophore structure takes shape via the action of the proteins CapZ and WHAMM .
During maturation the ATG12-ATG5-ATG16L1 complex recruits ATG8 proteins (particularly cleaved LC3B and GABARAP). These assists with morphing into the ‘bag’ shape of the autophagosome .
Among the ATG8 family members, LC3A, B, and C are mostly involved in autophagosome formation while GABARAP, GABARAL1, and GATE-16 are involved later in the maturation step .
While autophagy is generally viewed as a random process, engulfing cellular components indiscriminately, it appears to also have the ability to target specific components for degradation .
LC3 is reported to have a second function wherein it selectively incorporates cellular components that are exposing a specific structure (the LIR motif) .
Targeting of old parts of the endoplasmic reticulum and nuclear membrane is facilitated by FAM134 reticulon protein family .
NDP52 and OPTN are the main molecules involved in targeting mitochondria .
Components (proteins and bacterium) tagged for degradation (with ubiquitin) are targeted by p62 .
The cargo of an autophagosome is broken down and recycled by the contents of a lysosome. Attachment and fusing together of the two is facilitated by an interaction between ATG14, STX17, and SNAP-29 -.
Genes Involved in Turning Autophagy On and Off
mTOR suppresses the ULK complex (ULK1/2, ATG13, FIP200) which turns on the VPS34 complex and initiates phagophore ‘budding’ .
AMPK is a key sensor of intracellular energy under conditions of starvation or environmental stress. It can turn on autophagy by acting upon the ULK complex .
AMPK can also inactivate mTOR via the tuberous sclerosis complex (TSC) which prevents mTOR from blocking autophagy .
There are additional mechanisms for turning on and off autophagy that do not involve mTOR/AMPK. The inhibition of inositol monophosphatase and disruptions to the endoplasmic reticulum (causing the creation of faulty proteins) can both turn on autophagy [105, 104].
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