An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.

The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.

A large class of diseases that involve the heart or blood vessels, including stroke, hypertension, thrombosis, heart failure, atherosclerosis, and more. Cardiovascular disease is often caused by lifestyle factors. As such, up to 90 percent of cardiovascular disease may be preventable.^[1]

A broad term that describes periods of voluntary abstention from food and (non-water) drinks, lasting several hours to days. Depending on the length of the fasting period and a variety of other factors, intermittent fasting may promote certain beneficial metabolic processes, such as the increased production of ketones due to the use of stored fat as an energy source. The phrase “intermittent fasting” may refer to any of the following:

• Time-restricted eating
• Alternate-day fasting
• Periodic fasting (multi-day)

A broad range of disorders caused by the progressive death of neurons in the central and peripheral nervous systems. Common neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington’s disease, and multiple sclerosis. Although treatments are available for some neurodegenerative diseases, there are currently no cures.

A class of chemical compounds produced in plants in response to stressors. Polyphenols contribute to the bitterness, astringency, color, flavor, and fragrance of many fruits and vegetables. They often serve as deterrents to insect or herbivore consumption. When consumed in the human diet, polyphenols exert many health benefits and may offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. Dietary sources of polyphenols include grapes, apples, pears, cherries, and berries, which provide as much as 200 to 300 mg polyphenols per 100 grams fresh weight.

A chemical reaction that removes an acetyl functional group from a chemical compound. The presence of the acetyl functional group plays an important role in the synthesis, stability and localization of about 85% of human proteins.^[1] During fasting, falling acetyl CoA levels in the cytosol initiate protein deacetylation and initiates autophagy. In general, protein deacetylation, whether from so-called caloric restriction mimetics or nutrient deprivation, is an important general inducer of autophagy.

A polyphenolic compound produced in plants in response to injury or pathogenic attack from bacteria or fungi. Resveratrol exerts a diverse array of biological effects, including antitumor, antioxidant, antiviral, and hormonal activities. It activates sirtuin 1 (SIRT1), an enzyme that deacetylates proteins and contributes to cellular regulation (including autophagy). Dietary sources of resveratrol include grapes, blueberries, raspberries, and mulberries.

Resveratrol Autophagy ↑ Deacetylases (especially SIRT1) → ↓ Protein Acetylation → Autophagy

A polyamine (an organic compound having more than two amino groups) named for having been isolated in semen. Spermidine has since been found in a variety of different tissue types, as well as foods. It is best known for its role as a potential autophagy and longevity promoter with its effects having been demonstrated in yeast, flies, worms, and human immune cells.^[1]

↓ Acetyltransferase activity (especially EP300) → ↓ cytosolic Acetyl CoA → Autophagy

↓ mitochondrial transmembrane potential → ↑ ubiquitination → mitophagy (preferentially targeted)