On October 3, the 2016 Nobel Prize in medicine was awarded to Yoshinori Ohsumi, a 71 year old Japanese scientist at the Tokyo Institute of Technology, for his pioneering research on autophagy. His breakthrough work will advance efforts to prevent and treat cancers, diabetes, heart attacks, strokes, obesity, infections, and kidney, liver and lung diseases, as well as research on delaying aging and improving athletic performance.

What is Autophagy?
Autophagy means “self-eating”. When a cell is damaged or dies, the body quickly breaks down the dead cell’s parts (protein-making, power-generating, and transport systems) into small molecules that can be reassembled to be used for making new cell parts and supplying the energy to power these processes (Nature, Nov 2015;527(7576):105-9). Extensive research is going on today to figure out how to prolong lives and prevent diseases by improving the way that the body uses parts of dead cells to make new ones.

Nerve Damage: Many nerve damaging diseases, such as Alzheimer’s disease, Lewy body dementia or Huntington’s disease, appear to be caused by debris from dead cells accumulating in and damaging normal nerve cells. Current research is trying to work out how autophagy could get rid of these toxic particles from dead cells.

Heart Attacks: Autophagy recycles parts of dead cells to keep your body relatively free of these remnants. However, as you age, autophagy slows down, debris from dead cells builds up and the dead cell’s DNA and other cell parts leak into your bloodstream. Your body treats these breakdown products of cells as invading germs to turn on your immunity and cause inflammation to damage your arteries and heart muscle to increase risk for heart attacks and strokes (J Mol and Cel Cardiology, June 2015;83:44–54).

Cancer: Normal cells live only a fixed time and then are programmed to die. Cancer means that cells do not die at their programmed time and try to live forever. This is harmful because, for example, if breast cells do not die, they grow so numerous that they leave your breast and invade your lungs, brain, bones or other tissues to destroy them and kill you. Autophagy is part of the process of seeking out and killing damaged cells to prevent early cancer formation, and using the dead cell parts to make newer and healthier cells (Cancer Prev Res (Phila), July 4, 2011;(7):973-83). However, some tumors can adapt to use autophagy to provide them with basic building blocks so they can grow rapidly in the body (Experimental & Molecular Medicine, 2012;44:109-120). Damaged mitochondria are associated with most cancers, and autophagy can get rid of damaged mitochondria to turn cancer cells back into normal cells (J Clin Invest, Jan 2, 2015;125(1):42–46).

Infections: The same enzymes that break down your own dead cells can also break down the cells of viruses and bacteria that have been killed by your immune system. When you develop an infection, autophagy helps to turns on your immunity to kill germs and break down their debris for reuse and disposal (Nature, Jan 20, 2011;469(7330):323-35).

Aging: Aging is largely the result of cells losing their effective enzyme systems. Researchers are working to understand how to stimulate autophagy to eliminate defective cells and use their parts to produce new younger and healthier cells. Anything that interferes with the conversion of parts of dead cells to make parts of new cells can lead to the diseases associated with aging: cancers, nerve damage diseases, muscle damage and disease, metabolic diseases such as diabetes and obesity, and arterial diseases such as heart attacks and strokes.

How Calorie Restriction May Increase Autophagy to Prolong Life
Autophagy helps to explain why excess calories are associated with many diseases and premature death, whereas restricting calories while maintaining adequate nutrition is associated with preventing disease and prolonging lives. Four very recent studies show that restricting calories, even in non-obese people:
• reduces inflammation that causes cancers, heart attacks and premature death (Aging, July 2016)
• increases autophagy, the reuse and clearing of waste products from cells (PLoS Genetics, July 14, 2016)
• helps to prevent cancers (Cancer Research, July 14, 2016)
Conversely, increasing calorie consumption increases markers of inflammation and other predictors of heart attacks and diabetes (International Journal of Cardiology, 05/05/2016).

As cells in your body age, they gradually lose their ability to function and are at increased risk for mutations that can lead to cancers. To obtain the building blocks to make new cells and provide the energy to do so,
• you eat food, and
• your body uses autophagy in which old cells are broken down into their basic building blocks that are re-used to assemble the new cells.
Restricting food forces your body to increase autophagy to help the body rid itself of toxic waste products from dead cells. This would explain why restricting calories appears to prolong life, whereas taking in excess calories is associated with many diseases and premature death. It also probably explains many of the benefits of intermittent fasting; even brief periods of deprivation are enough to stimulate autophagy. For a more complete explanation see How Eating Less May Prolong Life

Checked 8/13/22