Autophagy: Definition, Process, Fasting, And Health Effects

What is autophagy?

Autophagy is the body’s natural process of removing old, damaged, and dysfunctional cells. The word autophagy is derived from two Greek words, “autos”, meaning “self” and “phagomai” meaning “to eat”, literally meaning “self-eating” or “self-devouring”. Autophagy helps to remove cellular debris, regenerate healthier cells, and promote survival in response to various stressors and toxins.

To achieve this process, a membrane is formed around material within cells that have been marked for disposal, and then it is delivered to the lysosome. The lysosome is full of digestive enzymes that can break down the cargo and then transport it from the lysosome back into the cytosol, the liquid inside cells, for use and repurposing. Autophagy normally occurs during periods of fasting, such as when we are asleep.

Yoshinori Ohsumi won the Nobel Prize for his discoveries in autophagy, which can protect against diseases like Parkinson’s, Huntington’s and certain forms of dementia. It has also been suggested that the process can be “switched on” by changes to our diet and lifestyle, such as fasting.

What is the process of autophagy?

Autophagy is a highly conserved cellular process that involves the targeted degradation of cellular components, such as defective organelles and aggregated misfolded proteins, through lysosomes. The process is triggered when cells are deprived of nutrients or oxygen or become damaged. Autophagy is a self-eating process that helps cells survive by maximising their energy resources. The process is initiated by the inhibition of the mechanistic target of rapamycin (mTOR) or activation of 5′ AMP-activated protein kinase (AMPK) and is regulated by transcription factor EB (TFEB). It begins with membrane nucleation and phagophore formation, followed by the elongation and maturation of the autophagosome before it fuses with the lysosome, where cargo is degraded and recycled. This process is essential for maintaining cellular and tissue homeostasis and can be divided into three major types: macroautophagy (autophagy), microautophagy and chaperone-mediated autophagy (CMA)..

How to increase autophagy naturally?

Step 1: Reduce your carb intake

Reducing your carb intake can increase autophagy, a process that helps the body to recycle and repair old, damaged cells. When your body is deprived of carbohydrates, it has no choice but to use fat as its main fuel source, resulting in ketosis. This state is associated with a high-fat and low-carb diet, such as the popular ketogenic diet. When your body is in ketosis, it increases autophagy – breaking down and recycling old, damaged cells. This process has been linked to the potential to fight cancerous tumours, lower the risk of diabetes, and protect against brain disorders, such as epilepsy. As a result, reducing your carb intake can increase autophagy and help you achieve optimal health.

Step 2: Exercise regularly

Exercise has been shown to positively affect autophagy, the body’s cleaning process and recycling of damaged cells. When people exercise, the components of their cells become damaged and inflamed, and the body responds to this by stimulating autophagy. Studies have shown that exercise increases autophagy in human skeletal muscles. A 2012 study found that when mice ran on a treadmill, the rate of autophagy within their cells drastically increased. Some lifestyle recommendations, such as reducing protein on certain days, eating carbohydrates later in the day, and periods of high-intensity exercise, have been proposed to increase autophagy further. Ultimately, regular exercise is a great way to help the body cleanse and rejuvenate itself and can be a beneficial tool in managing one’s overall health.

Step 3: Take a Rhodiola supplement

A Rhodiola supplement can increase autophagy by providing key antioxidants and adaptogenic compounds that help promote the body’s natural detoxification process. Autophagy is a process that helps reduce inflammation, boosts immunity, and slows down the aging process. Rhodiola helps boost energy levels, which can help with the metabolic processes needed for autophagy. Additionally, Rhodiola can help reduce stress levels, which is necessary for the body to enter autophagy.

Step 4: Load up on green vegetables and leafy greens

Step 1: Incorporate leafy greens and green vegetables into your diet. Choose nutrient-dense greens like kale, spinach, broccoli, Swiss chard, and collards.

Step 2: Consume polyphenols, which are found in a variety of fruits and vegetables. Polyphenols are known to induce autophagy. Examples of polyphenols include resveratrol, quercetin, green tea catechins, curcumin, and grape skins.

Step 3: Follow an Ayurvedic diet, which may improve overall health. This includes eating seasonal foods, cooking with spices, and syncing your meals to your circadian rhythm.

Step 4: Eat foods that contain polyphenols that promote autophagy, such as green tea, grape skin, nuts, onions, apples, berries, turmeric, soybeans, milk thistle, and eggs.

Step 5: Incorporate high-intensity exercise into your routine, as this has been shown to induce autophagy.

By following these steps, you can increase autophagy in your body and promote overall health and wellness.

Step 5: Add slow-release foods to your diet

Adding slow-release foods to your diet can help increase autophagy, the body’s natural process for cleaning out old, damaged cells and tissues. Slow-release foods are digested slowly and release energy over long periods. This can help the body maintain its natural fasting state, which is the best way to stimulate autophagy. Consuming slow-release foods like oats, beans, lentils, and quinoa can reduce the number of insulin spikes caused by eating, allowing the body to maintain a fasting state for longer periods. Slow-release foods can also help reduce cravings, maintain a healthy weight, and improve mental clarity. Additionally, research has found that regularly engaging in short periods of fasting, such as 16-hour fasts three times a week, can positively affect weight loss, blood pressure, and improved lean muscle mass.

Step 6: Get enough sleep

Sleeping is important for activating and maintaining the body’s autophagy process. Autophagy is the natural process of recycling and repairing damaged cells, and research has shown that it can be stimulated by exercise and fasting. Sleep is crucial in this process as it allows the body to rest and recover, which is essential for autophagy. Studies have shown that lack of sleep can lead to reduced levels of autophagy, making it harder for the body to repair itself. In addition, lack of sleep can lead to increased cortisol levels, a hormone inhibiting autophagy. Therefore, getting enough sleep is important for maintaining optimal levels of autophagy in the body.

Step 7: Keep a food journal

Keeping a food journal can help you increase autophagy by helping you to become more mindful of what you eat and when. This can help you stick to a balanced diet of seasonal foods cooked with spices and matched to your circadian rhythms, as the Ayurvedic diet recommends. Additionally, eating 16-hour fasts three times a week, reducing protein on some days, eating carbohydrates later in the day, and periods of high-intensity exercise may help increase autophagy. Eating healthier, tracking your food intake and exercise, and better understanding your body’s needs can all help increase autophagy.

Step 8: Try intermittent fasting

Intermittent fasting has been shown to increase autophagy, the body’s process of breaking down and recycling old and damaged cells. Autophagy helps to remove toxins from the body, boosting the immune system and improving overall health. Research has found intermittent fasting may make cancer treatments more effective, protect normal cells, and reduce side effects. In addition, animal studies have demonstrated that intermittent fasting can improve cognitive function, brain structure, and neuroplasticity. However, it is not yet clear if autophagy is the cause of these benefits. Therefore, it is important to consult a doctor before starting any intermittent fasting regimen.

Step 9: Take a multivitamin

It is important to take a multivitamin when attempting to increase autophagy, as the process can deplete the body of certain important nutrients, including magnesium, zinc, selenium, and vitamins A and D. Taking a multivitamin ensures that these essential nutrients are replaced and can help to support the process of autophagy further. Research suggests that taking a multivitamin may help to improve the efficacy of autophagy, as it can increase the levels of antioxidants in the body, which may help to protect against cell damage. Thus, taking a multivitamin when attempting to increase autophagy is an important step in ensuring the success of the process.

Step 10: Detoxify regularly

To maximize the body’s natural detoxifying process, autophagy, you should consider the following:

• Regular Exercise: Regular exercise can help trigger autophagy, the body’s natural detoxifying process.
• Running: Running for 30 to 80 minutes has been found to increase autophagy in mice drastically.
• Intermittent fasting: Intermittent fasting can also activate autophagy, with fasting for 16 to 24 hours being a good starting point.
• Medications: Medications like stiripentol, which mimics ketosis, can also activate autophagy but should only be taken under the supervision of a doctor.

Autophagy is an important process for keeping our cells healthy, and regular exercise and intermittent fasting can help to activate it. Always consult your doctor or nutritionist before making any major dietary changes, and remember that even short periods of exercise and fasting can still be beneficial.

Benefits of Autophagy

Let’s discuss some of the major benefits of autophagy:

1. Cleansing of Cells and Toxins

Autophagy is a natural cleaning process that helps keep cells healthy by clearing away damaged cell parts and eliminating waste, oxidative stress, and foreign agents. It also helps to convert nutrients into energy and improve the transmission of nerve signals in the brain. Autophagy is essential for keeping cells healthy and in good working order and helps to avoid the premature deterioration and aging of cells. By recycling old cell parts and eliminating toxins, autophagy helps to keep the body functioning optimally and maintain a healthy balance.

2. Protection Against Aging and Disease

Autophagy is a critical process for maintaining healthy cells and tissues, and its dysregulation can lead to age-related diseases. Studies have suggested that inducing autophagy may have beneficial effects in reducing the risk of chronic diseases and extending life span. Specifically, autophagy is believed to reduce oxidative stress, DNA damage, and other cellular insults that can lead to disease. Additionally, autophagy may reduce inflammation, a key factor in developing many chronic diseases. Furthermore, autophagy may protect against neurodegenerative diseases like Alzheimer’s and Parkinson’s by removing toxic proteins and aggregates. By reducing the risk of harm from such proteins, autophagy may be able to slow down the aging process and improve overall health. Finally, autophagy may help keep cells healthy by removing damaged organelles, promoting cell survival, and reducing cancer risk. In conclusion, autophagy could be useful for reducing the risk of aging and disease.

3. Improvement of Muscle Function

Autophagy helps improve muscle function by triggering the body’s recycling process when cells become damaged and inflamed from exercise. The process of autophagy recycles cellular components and helps restore muscle homeostasis and regeneration. Studies have found that short-term caloric restriction increases the number of muscle stem cells, which helps improve muscle regeneration and transplantation efficiency. Autophagy is also impaired in aged muscle cells, but stimulating autophagy in old satellite cells has been found to improve stem cell function and prevent aging-induced senescence.

4. Increased Energy Production

Autophagy is an important factor in energy production in the body. During autophagy, the body’s cells are broken down and recycled, which helps to provide energy for necessary bodily functions. This process helps reduce waste buildup and keeps the cells healthy and functioning. Research has also shown that autophagy may be beneficial in controlling diabetes, as it helps regulate insulin production in the pancreas. Regular exercise can help activate autophagy, as it stresses the body and damages the muscles, causing the body to rush to heal them. This helps to keep the cells healthy and functioning, which provides more energy for the body to use.

5. Improved Memory and Cognitive Function

Autophagy, the body’s process of breaking down and recycling old or damaged cells, has been linked to improved memory and cognitive function. According to Dr David Rubinsztein, professor of molecular neurogenetics at the University of Cambridge and UK Dementia Research Institute, evidence from experiments in mice suggests that autophagy can contribute to living longer and being in better overall shape. However, how this translates to humans or how long they need to fast to experience the benefits is unclear. But you can not deny that fasting stimulates autophagy, and other studies have backed up its benefits.

6. Reduction in Inflammation

Autophagy is a process by which damaged or old cells are broken down and recycled, and it has been found to play a role in controlling inflammation and boosting immunity. Clearing out damaged cells and foreign materials helps to decrease inflammation, improve the transmission of nerve signals in the brain, keep the immune system functioning normally, and support the detection of cancer and other foreign agents by the immune system. Exercise has been found to increase autophagy in human skeletal muscles, which suggests that people can use exercise to trigger autophagy and help reduce inflammation.

7. Increased Cell Survival Rates

Autophagy increases cell survival rates by clearing away damaged parts, thus keeping cells healthy and in good working order. Autophagy serves as a cellular defence mechanism to maintain energy production, recycle ATP, and reduce stress on the cell. Induction of autophagy by miRNA-4673, for example, is a pro-survival mechanism that improves the resistance of cancer cells to radiation and can enhance the effectiveness of anticancer therapies. In addition, autophagy can limit inflammation and prevent cancer cell damage, thus promoting tumorigenesis, contributing to the aggressiveness of cancers, and facilitating metastasis.

8. Reduced Risks of Tumour Formation and Growth

Autophagy has been found to reduce the risks of tumour formation and growth by decreasing oxidative stress, keeping DNA and genes stable, preventing premature cell deterioration and aging, decreasing inflammation, improving the transmission of nerve signals in the brain, keeping the immune system functioning normally, and supporting detection of cancer and other foreign agents by the immune system. Autophagy also plays a role in removing damaged mitochondria and maintaining mitochondrial function, which is required for tumorigenesis. Furthermore, autophagy can help eliminate pathogens and other foreign materials, improve the conversion of nutrients into energy, and eliminate waste, which can benefit overall cellular health and reduce the risk of tumour formation or growth.

9. Improved Liver Health

Autophagy is believed to play an important role in maintaining liver health and may help to protect liver cells from damage caused by drug and alcohol consumption. Studies have shown that autophagy may help to prevent the progression of several liver conditions, such as Wilson’s Disease, acute liver injury, nonalcoholic fatty liver disease, and chronic alcohol-related liver disease. Furthermore, autophagy has been linked to increased cell survival and decreased inflammation, which can help to reduce the risk of liver damage.

10. Improved Gastrointestinal Health

Autophagy, a process of self-digestion, is essential for maintaining optimal gastrointestinal health. Autophagy helps regulate the breakdown of proteins and the recycling of old cells and organelles.

With regular autophagic activity, the body can better break down nutrients, reduce inflammation, and reduce food cravings. Additionally, autophagy has been linked to improved fat metabolism, aiding weight management. Intermittent fasting, time-restricted feeding and fasting during Ramadan, and the ketogenic diet are all methods that can promote autophagy to improve gastrointestinal health.

How does fasting affect autophagy?

Fasting has been shown to induce autophagy, a process in which cells break down and recycle damaged parts. This occurs when the body is stressed, such as when a person fasts or reduces calorie intake. When people limit the amount of food that goes into their bodies, their cells receive fewer calories than they need to function correctly, so they must work more efficiently.

How fasting affects autophagy:

Note: The data presented in this table is based on current scientific understanding and may be subject to change as more research is conducted. Additionally, individual responses to fasting may vary based on age, sex, and overall health.

Studies have shown that fasting and calorie restriction can induce autophagy in the body, including in the brain, although it is not yet known which cells respond to these triggers. However, protein-based beverages may decrease autophagy activity, so people trying to induce autophagy through fasting should be aware that this may not target fat cells.

FAQs

What is Autophagy?

Autophagy is the body’s recycling process and cleaning out old and damaged cell parts. A self-preservation mechanism helps the body remove dysfunctional cells and recycle parts for cellular repair and cleaning. Autophagy, also referred to as “self-eating” or “self-devouring,” is the body’s way of cleaning out damaged cells to regenerate healthier ones. This process is beneficial for overall health as it helps to clear out debris, regulate function and promote adaptation as a response to stressors and toxins found in cells. Autophagy occurs when cells are deprived of nutrients or oxygen or damaged in some way. It is also known to happen during periods of fasting, most often while we are sleeping. The word “autophagy” is derived from two Greek words, “autos” meaning “self” and “phagomai” meaning “to eat”.

How does Autophagy work?

• Autophagy is a natural process by which cells clean out or recycle unwanted or damaged molecules within them.
• The process begins with the cell marking any unwanted or damaged organelles for removal.
• These organelles are then surrounded by a membrane, which seals them off like a garbage bag, becoming an autophagosome.
• The autophagosome then moves towards a lysosome, a small acidic bag of powerful enzymes.
• When the two fuse, their contents mix and the enzymes break down the rubbish into recycled nutrients that the cells can reuse.

What role does Autophagy play in cellular health?

Autophagy is a fundamental cell survival mechanism that allows cells to adapt to metabolic stress by degrading and recycling intracellular components to generate macromolecular precursors and produce energy. It plays an essential role in maintaining cellular and tissue homeostasis and is involved in various processes, such as stem cell quiescence, activation, differentiation, and self-renewal. Autophagy recycles damaged cell parts into fully functioning cell parts, removes nonfunctional cell parts that take up space and slow performance and destroys pathogens in a cell, like viruses and bacteria. Autophagy also plays an important role in aging and longevity as it decreases with age, leading to a build-up of cellular junk parts and cells that don’t function at their best. In sum, autophagy is a natural bodily process responsible for cleaning out our cells and preventing chronic diseases.

How does Autophagy affect stem cells?

• Autophagy is critical in stem cell biology, affecting stem cell maintenance, mitochondrial content, energy production, and epigenetic programming.
• Autophagy helps protect stem cells against metabolic stress and prevent genome instability, cell death, and senescence.
• Autophagy regulates stem cell quiescence, activation, differentiation, and self-renewal.
• Targeting autophagy can be a therapeutic strategy to modulate stem cell function.
• Inducing autophagy can improve aged stem cell function, promote the reprogramming of somatic cells into induced pluripotent stem cells (iPSC), and facilitate the direct conversion of somatic cells into tissue-specific stem cells.
• Inducing autophagy can also improve stem cell transplantation therapies.
• Inhibiting autophagy in cancer stem cells can eliminate tumour-initiating cells and prevent cancer treatment resistance.

How does Autophagy affect tumour cells?

Autophagy has been shown to have both a tumour suppressor and tumour-promoting effect on cancer cells. Early in the development of tumours, autophagy can aid in tumour suppression by removing damaged cells, inhibiting DNA damage, maintaining genome stability, and preventing inflammation. However, once the tumours have progressed to a more advanced stage, autophagy can promote the growth and survival of the tumours by removing toxic oxygen radicals, maintaining mitochondrial function, and sustaining metabolism and survival in stressful conditions. Autophagy can also facilitate metastasis, which is a major cause of cancer-related deaths. Therefore, autophagy plays a major role in determining the fate of tumour cells and their likelihood of survival.

How does Autophagy affect organ health?

Autophagy plays an important role in organ health by removing damaged proteins and organelles. Dysfunctional autophagy can accumulate abnormal and damaged proteins and organelles, and the formation of intracellular aggregates impairs autophagy’s ability to remove infectious pathogens. In cancer, autophagy can play different roles depending on the stage of the tumour and the presence of an immune system. Removing waste products can help protect cells from age-related diseases and may help reduce the risk of tumours.

What effect does Autophagy have on aging?

Autophagy has a complex relationship with aging. Studies have suggested that inducing autophagy in animals can lead to an extended lifespan and improved health during aging. However, as we age, the autophagy machinery decreases in abundance and functionality, making it harder to turn on and reducing effectiveness. Therefore, an age-dependent decline in autophagy contributes to the aging process. Imbalanced or impaired autophagy can promote pathological aging and disease. To achieve the best results for promoting health, it is necessary to find approaches that can fine-tune autophagy to the right levels, at the right time and in the right tissues. Therefore, autophagy can help slow down aging and contribute to the aging process, depending on its regulation and balance.

What is the role of mTOR in Autophagy?

The mammalian target of rapamycin (mTOR) is a kinase that serves a critical role in regulating autophagy. mTOR acts as a negative regulator of autophagy, inhibiting the formation of the autophagy initiation ULK1 Ser/Thr kinase protein complex. mTOR achieves this by directly phosphorylating ULK1 at serine residue (Ser) 757, which prevents ULK1 from interacting with AMP-activated protein kinase (AMPK). This means that under nutrient-rich conditions, mTOR can prevent autophagy from occurring and instead allows the cell to focus on growth and metabolism.

What are the benefits of Autophagy?

The benefits of autophagy include anti-aging principles, enhancing lifespan, protection against cellular stress, recycling cellular material and proteins, removal of toxic proteins that are attributed to neurodegenerative diseases, providing energy and building blocks for cells that can still benefit from repair, regeneration and healthy cells, potentially preventing and fighting disease, and potentially helping with longevity, weight loss, and the prevention of certain chronic diseases. Autophagy may be induced through fasting, caloric restriction, a low-carbohydrate diet, and exercise.

How can I activate Autophagy?

Step 1: Fast: Fasting means you stop eating for a certain amount of time and deprive your body of nutrients, forcing it to repurpose cell components.

Step 2: Restrict your calories: Restricting your calories means decreasing the number of energy units, or calories, your body consumes. This forces your cells into autophagy to compensate for the lost nutrients.

Step 3: Switch to a high-fat, low-carb diet: This type of diet, commonly referred to as a keto diet, changes the way your body burns energy, so instead of burning carbs or sugar for energy, it burns fat instead. This switch can trigger autophagy.

Step 4: Exercise: Exercise stimulates processes that increase the activity of ATGs, such as stressing your skeletal muscles. Exercise can induce autophagy, depending on the type of exercise you’re doing and its intensity.

Resources

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871782/