Does Fasting Really Trigger Autophagy? Dr. Badran Answers

Autophagy is a vital process in which the body’s cells “clean out” any unnecessary or damaged components. The term “autophagy” derives from the Ancient Greek for “self-eating.”

Researchers have linked autophagy to several positive health effects. They also believe that a person might be able to induce autophagy by fasting.

What is autophagy?

Autophagy is a lysosome-dependent cellular degradation program that responds to a variety of environmental and cellular stresses. It is an evolutionarily well-conserved and essential pathway to maintain cellular homeostasis, therefore, dysfunction of autophagy is closely associated with a wide spectrum of human pathophysiological conditions including cancers and neurodegenerative diseases.

A person’s body contains trillions of cells. Over time, unwanted molecules can build up inside them; sometimes, this can damage some of their parts. Autophagy is a natural process that responds to this problem. During autophagy, the cells remove these unwanted molecules and dysfunctional parts. Sometimes, autophagy destroys some of these molecules and parts. Other times, the cell recycles these parts into new components.

The process of autophagy activation is strictly regulated by 18 different autophagy-related genes .

Mitochondrial Autophagy

Mitochondria is the Powerhouse of the Cell. Autophagy is a key determinant for mitochondrial health and proper cell function. Mitochondrial number and health are regulated by mitophagy, a process by which excessive or damaged mitochondria are subjected to autophagic degradation. Mitochondria can also substantially influence the autophagic process. The mitochondria's ability to influence and be influenced by autophagy places both elements (mitochondria and autophagy) in a unique position where defects in one or the other system could increase the risk to various metabolic and autophagic related diseases.

Autophagy Functions

Housekeeping roles – these roles involve removal of aggregated and erroneously folded or formed proteins and removal and clearance of damaged organelles or cellular components. The damaged cell organelles include mitochondria from old and infirm cells and also the endoplasmic reticulum.

Role in cellular stress – autophagy is a response to cellular stress. It regulates the processes that occur when there is nutrient deprivation and cellular stress.

Embryonic development – autophagy plays an important role in development of the embryo by maintain a critical balance of energy levels and sources.

Autophagy plays an important role in the survival of cellular organisms. When there is starvation or nutrient deprivation, the process of autophagy is triggered. This gives rise to formation of double membrane autophagic vacuoles, also known as autophagosomes that transport the cargo from the cytoplasm to the lysosome for degradation.

Health Effects

As emphasized by the 2016 Nobel Prize in Physiology or Medicine, autophagy is now considered to be the major mechanism by which cells eliminate unnecessary or toxic cellular constituents.

Basal autophagy protects the health of cells and tissues through replacing expired or damaged cellular components with new ones. Notably, abnormal functional status of autophagy (excessive activation or deficiency) can lead to the occurrence of many human diseases, such as cancer, cardiovascular diseases, obesity, diabetes, and aging. Recent studies have reported its role and regulation in obesity-related complications.

A recent study surveys existing research into autophagy and cancer. It finds that while autophagy can help to stall the development of cancer cells, it may also promote their growth, depending on the stage of the tumor.

Autophagy may help protect liver cells from drug- and alcohol-induced liver injury. Autophagy plays a role in many liver functions and could prevent the progression of several liver conditions.

Autophagy in Immunity

Autophagy is now emerging as a spotlight in trafficking events that activate immunity. As a central player in the immunological control of pathogen clearance, it facilitates innate pathogen detection and antigen presentation, as well as pathogen clearance ,lymphocyte survival and homeostasis, and mediate cytokine production.

Autophagy also seems to play an essential role in the immune system by cleaning out toxins and infectious agents. There is evidence that autophagy may improve the outlook for cells with infectious and neurodegenerative diseases by controlling inflammation.

Autophagy helps kill cells that are infected or invaded by foreign pathogens. Thus it helps contain the infection and may act as part of the immunity of the cellular organism.

Link to Fasting

Autophagy occurs naturally within the body, but many people wonder if they could induce autophagy using specific triggers. Fasting is a possible trigger of autophagy. When somebody fasts, they voluntarily go without food for extended periods — hours or sometimes a day or more. Fasting is different from traditional calorie restriction. When a person restricts their calories, they reduce their regular intake of food. Fasting may or may not result in calorie restriction, depending on how much food a person consumes during feeding periods. Both fasting and calorie restriction can induce autophagy.

Fasting and calorie restriction puts the body’s cells under stress. When a person limits the amount of food that goes into their body, their cells receive fewer calories than they need to function correctly. When this happens, the cells must work more efficiently. In response to the stress brought on by fasting or calorie restriction, autophagy causes the body’s cells to clean out and recycle any unnecessary or damaged parts.

Autophagy and Brain Plasticity

Growing evidence suggests that autophagy is essential for both developmental and adult neural stem cell maintenance, proliferation, and differentiation. In the mature CNS, autophagy plays a role in plasticity through actions within the axon, dendritic spine, and during synaptic assembly. Defects in autophagy and its role in neurogenesis and neuronal plasticity may contribute to developmental disorders such as autism spectrum disorder and attention deficit hyperactivity disorder, memory deficits, and psychiatric disorders such as depression.

Autophagy plays a central role in brain function and maintaining the health of your nerve cells. Interestingly, a 3-year study linked intermittent fasting to improved brain function in older adults with mild mental impairment. Another study including 883 older adults observed similar findings, noting that the beneficial effects associated with intermittent fasting could be due to several factors, including autophagy.

In addition to increasing autophagy, ketones are used as an effective source of energy for the brain and could promote brain function.

Autophagy is a highly conserved intracellular clearance pathway in which cytoplasmic contents are trafficked to the lysosome for degradation. Within neurons, it helps to remove damaged organelles and misfolded or aggregated proteins and has therefore been the subject of intense research in relation to neurodegenerative disease.

Exercise Can Induce Autophagy

Physical exercise is a newly defined inducer of autophagy in vivo. Exercise induces autophagy in multiple organs involved in metabolic regulation, such as muscle, liver, pancreas and adipose tissue. Exercise also puts the body’s cells under stress. When people exercise, the components of their cells become damaged and inflamed. Our cells respond to exercise with autophagy. This suggests that people might be able to use exercise to trigger autophagy.