Autophagy and fasting

• The sirtuin pathway: Sirtuins are a family of enzymes that sense the levels of NAD+ (a coenzyme involved in energy metabolism) in the cells. When the cells are low on NAD+ due to fasting, sirtuins are activated and deacetylate several targets that regulate autophagy.
• The p53 pathway: p53 is a protein that acts as a tumor suppressor and a stress sensor in the cells. When the cells are under stress due to fasting, p53 is activated and transcribes several genes that induce autophagy.

By activating these pathways, fasting stimulates the formation of autophagosomes (the vesicles that engulf the cellular material to be degraded) and their fusion with lysosomes (the organelles that contain the enzymes that digest the cellular material). Fasting also enhances the expression and activity of lysosomal enzymes, which increases the efficiency of autophagic degradation.

What Are the Benefits of Fasting-Induced Autophagy?

Fasting-induced autophagy can have various benefits for health and disease prevention. Some of these benefits include:

• Improving metabolic health: Fasting-induced autophagy can improve glucose and lipid metabolism, insulin sensitivity, mitochondrial function and energy expenditure. Autophagy can also prevent or reverse fatty liver disease, a common metabolic disorder associated with obesity and diabetes.
• Enhancing neuroprotection: Fasting-induced autophagy can protect the brain from oxidative stress, inflammation, excitotoxicity and protein aggregation. Autophagy can also promote neuronal survival, plasticity and regeneration. Autophagy may also prevent or delay neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Huntington’s.
• Boosting immunity: Fasting-induced autophagy can modulate immune responses by eliminating pathogens, clearing damaged or senescent immune cells and regulating cytokine production. Autophagy can also enhance the function of natural killer cells, which are important for anti-tumor immunity.
• Extending lifespan: Fasting-induced autophagy can delay aging and increase longevity by reducing oxidative damage, inflammation, DNA damage and cellular senescence. Autophagy can also activate stem cells and promote tissue regeneration. Autophagy may also mimic the effects of calorie restriction, which is known to extend lifespan in various organisms.

How to Practice Fasting for Autophagy?

There is no definitive answer to how long or how often one should fast to induce autophagy. The optimal fasting regimen may vary depending on individual factors, such as age, health status, lifestyle and goals. However, some general guidelines are:

• Start gradually: If you are new to fasting, start with shorter and less frequent fasts, such as 12 hours overnight or 16 hours twice a week. Gradually increase the duration and frequency of your fasts as you become more comfortable and experienced.
• Choose a fasting method that suits you: There are different types of fasting methods, such as water fasting, juice fasting, dry fasting or intermittent fasting. Choose a method that fits your preferences, schedule and needs. For example, if you have a busy or irregular lifestyle, intermittent fasting may be more convenient than water fasting.
• Listen to your body: Fasting should not cause extreme hunger, fatigue, weakness or discomfort. If you experience any adverse symptoms or signs of dehydration or electrolyte imbalance during your fasts, such as headache, dizziness, nausea or muscle cramps, stop fasting and consult your doctor. You may need to adjust your fasting duration, frequency or method.
• Break your fasts properly: When you break your fasts, avoid overeating or consuming unhealthy foods. Eat slowly and moderately, and choose nutritious foods that are easy to digest. For example, you can start with some fruits, vegetables or soups before moving on to more solid foods. Drink plenty of water and fluids to rehydrate yourself.
• Combine fasting with other healthy habits: Fasting alone is not enough to induce autophagy or achieve optimal health. You should also follow a balanced diet that is rich in antioxidants and anti-inflammatory foods, such as fruits, vegetables, nuts, seeds, legumes, whole grains, fish and olive oil. You should also avoid or limit processed foods, added sugars, refined carbohydrates, saturated fats and alcohol. Additionally, you should exercise regularly, manage your stress levels, get enough sleep and avoid smoking or other harmful substances.