Autophagy & Longevity

Autophagy (pronounced as aw-TAW-pha-gee), literally means eating oneself. When Yoshinori Ohsumi discovered the mechanism of autophagy in baker’s yeast and received a Nobel Prize in 2016, it started a wave of studies and research on autophagy in animals and ultimately human health(1). Autophagy allows cells to recycle their intracellular contents to “rejuvenate” or simply self cleanse. It is decluttering in the cellular level, getting rid of old, nonessential organelles to make room for new ones. Thus, allowing cells to be more efficient. With age, the ability of the cells to “self clean” declines. The accumulation of “junk” in the cells affect their functions, particularly in the release of chemicals (cytokines) involved in immunity and inflammation.

Autophagy was found to be an important in suppressing tumor development, preventing neurodegeneration and prolonging life in mice. It improved immunity, metabolism, decreased inflammation, thus better cardiovascular health. Basically, all the benefits from fasting, mentioned in my previous blog, were attributed to autophagy. More and more data are emerging showing that the loss of autophagy may be associated with a myriad of diseases like diabetes, hypertension, heart disease, inflammatory bowel disease, dementia as well as cancer. So, is it just a new popular term in the world of diet and anti-aging, or is it the holy grail for longevity?

Autophagy can be triggered when the body is stressed or when nutrition is limited. One way to activate autophagy is fasting or caloric restriction. The amount of time for autophagy to begin differs for everyone, and depends on multiple factors including age, sex, genetic and so on. In animal studies, fasting for 12-72 hours will put the body in the ketotic state and start the process of autophagy. However, there is no concrete data yet on the type of fasting that would turn on autophagy in human. Ongoing studies are trying to find out more on the risks and benefits of the different kinds of intermittent fasting, periodic fasting and caloric restrictions diets on human.

Exercise is another way to stimulate autophagy. The benefits of exercise on metabolic and cardiovascular health are well known. Exercise is a kind of “stress” to the body by making the cells temporarily lack oxygen and nutrients, putting cells into a state of oxidative stress and chemical imbalance. Autophagy is the body’s response to the stress by improving the power house of the cells - mitochondria, and cleaning up unnecessary protein which can be toxic. So, exercise improves cellular oxygenation and energy level through maintaining mitochondrial health, protein turnover and metabolism.(2)

Another way to activate autophagy is through medications, but the natural way through a healthy lifestyle should always be tried first.

Even though there seems to be a lot of good news about autophagy, we still do not have the hard data to prove that autophagy can prevent diseases and prolong life in human. Only time will tell whether autophagy will pan out to be the miracle for longevity and good health. Meanwhile, there is no harm to eat healthy and exercise!

*Even though intermittent fasting is relatively safe, it may not be suitable for everyone. Do consult with a physician whether this would be recommended for you

References:

1. B Levine, DJ Klionsky. Autophagy wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in baker's yeast fuel advances in biomedical research. Biological Sciences 2016;114(2)201-205

2. Condello M, Pellegrini E, Caraglia M, Meschini S. Targeting Autophagy to Overcome Human Diseases. Int J Mol Sci. 2019 Feb 8;20(3):725. doi: 10.3390/ijms20030725. PMID: 30744021; PMCID: PMC6387456.

3. Longo VD, Di Tano M, Mattson MP, Guidi N. Intermittent and periodic fasting, longevity and disease. Nat Aging. 2021 Jan;1(1):47-59. doi: 10.1038/s43587-020-00013-3. Epub 2021 Jan 14. PMID: 35310455; PMCID: PMC8932957.