The Protective Effects of Autophagy

There’s no doubt that diet and lifestyle affect our healthspan – this refers to the number of healthy years that you live, as opposed to lifespan which is simply the number of years that you live, regardless of quality of life. Autophagy is gaining interest in those seeking to increase their healthspan. The word autophagy is derived from the Greek Auto-Phagein meaning self eating. Autophagy is when the body breaks down older cells and cellular organelles to create new cells that produce energy more efficiently. A key driver of autophagy is cellular stress which occurs during fasting and exercise. At these times the body needs raw materials to produce energy in order to survive. Clearing cellular damage through autophagy seems to be a common denominator in many healthspan-extending techniques (1). Here we’ll look at autophagy and disease, the possible benefits of autophagy and some of the mechanisms involved in autophagy.

You’ll also want to read the blog posts on Tips for Stimulating Autophagy and Possible Problems with Fasting and Autophagy to get the full picture.

The Evolution of Autophagy

It was common for our ancient ancestors to undergo high intensity activity, excessive heat and cold and long periods without food. These demands stimulated a regular dose of autophagy.

Autophagy and Disease

Defects in autophagy regulation are believed to play a central role in a number of diseases, including neurodegenerative diseases, cancer, infections and metabolic diseases. Autophagy upregulation may have a role in preventing diseases such as cancer, neurodegeneration, cardiovascular disease, diabetes, liver disease, autoimmune diseases and infections (2). It should be noted that both induction and inhibition of autophagy may be beneficial in the treatment of cancer (3).

The Benefits of Autophagy

Autophagy is beneficial because it:

• Gets rid of senescent cells – these are older cells that are not functioning at a high level. They produce energy inefficiently, create metabolic waste and promote inflammatory conditions in the body. While the development of senescent cells is a normal process, removing them through autophagy is beneficial to health.
• Improves mitochondrial health – the mitochondria within cells produce energy. Without autophagy we end up with a large number of dysfunctional mitochondria that are metabolically inflexible. Autophagy may keep the cell in tact but degrade the dysfunctional mitochondria and reuse the raw materials to form new, metabolically flexible mitochondria. This mitochondrial recycling is called mitophagy.
• Eliminates viruses – viruses live inside the cells and impact the metabolism and expression of cellular genetics. While a strong immune system helps to put viruses into a dormant state, it doesn’t actually get rid of them. Autophagy eliminates the infected cells and reduces viral activity.
• Reduces cellular apoptosis – older cells eventually undergo a programmed cell death called apoptosis. This process leads to metabolic waste and may induce inflammation. Autophagy reduces this process by recycling the old cells.
• Longer periods of food restriction reduce the amount of energy available for basic bodily processes. At these times the liver and muscles start using energy from fat instead of sugars. This can be a good thing as having a flexible metabolism that is able to switch between using fat and sugars to obtain energy is beneficial. Having a less flexible metabolism leads to a higher risk of insulin resistance. The less flexible your metabolism is, the more difficult you are likely to find intermittent fasting.

The Benefits of Autophagy Around the Body

• Autophagy in our muscles makes them stronger and more resilient to wear and tear.
• Autophagy in our intestinal lining makes us less susceptible to gut inflammation and leaky gut syndrome.
• Autophagy on our skin makes it more resilient and less likely to develop eczema, acne and signs of ageing.
• Autophagy in our brain cells leads to improved mood, memory and mental processing and reduces the risk of developing dementia and other neurodegenerative conditions.

Medical manipulations that increase life span in model organisms often stimulate autophagy, whilst inhibiting autophagy compromises the longevity-promoting effects of mechanisms such as caloric restriction, Sirtuin 1 activation and the administration of rapamycin, resveratrol and spermidine (4). Other pathways that are involved in autophagy include:

The mTOR pathway – mTOR stands for Mammalian Target of Rapamycin (mTOR). The mTOR pathway is associated with the regulation of growing tissues in the body. Temporary mTOR elevations are great for building muscle and fat burning, but chronically elevated mTOR is associated with an increased risk of chronic disease and cancer.

The AMP-K pathway – AMP-K stands for adenosine monophosphate-activated protein kinase. AMP-K is an enzyme that plays a crucial role in metabolism, glucose, lipid transport and overall health.

Spermidine – a natural polyamine whose concentration declines during ageing. Spermidine extends the lifespan of yeast, flies and worms, and human immune cells and inhibits oxidative stress. Autophagy is crucial for spermidine to have its longevity enhancing effects (5).

Autophagy needs to be balanced with growth. Read more about this in the blog post Tips for Stimulating Autophagy.

References

1. Nat Cell Biol. 2010 Sep;12(9):842-6. Can autophagy promote longevity? Madeo F et al.

2. J Pathol. 2010 May;221(1):3-12. Autophagy: cellular and molecular mechanisms. Glick D et al. .

3. 2011 Sep 2;146(5):682-95. Autophagy and aging. Rubinsztein D et al.

4. Life Sci. 2017 Nov 1;188:53-67. Autophagy: The spotlight for cellular stress responses. Ravanan.

5. Nat Cell Biol. 2009 Nov;11(11):1305-14. Induction of autophagy by spermidine promotes longevity. Eisenberg T et al.