Autophagy is a process in which our cells remove all the accumulated junk and waste, like damaged DNA or proteins. This process shields cells from damage and helps them stay healthy. Autophagy can also help prolong lifespan and prevent many age-related diseases from happening.
Autophagy also offers cells a source of food in times of prolonged hunger. When we fast for at least 24 hours, we induce autophagy in cells and help them eat their parts quicker to survive. This process can also be induced by exercise and supplements like spermidine.
Do you want to learn more about autophagy for longevity, and how to induce it? Keep reading and learn more about autophagy!
What is autophagy?
Autophagy is a cellular process that "removes" all cellular debris, meaning all old and damaged cell parts. It's a way in which cells clean themselves, and it actually comes from the Greek words "autos" (self), and "phagomai" (eating).
The autophagy process allows cells to remove any old organelles, proteins, or membrane parts that don't function anymore. For example, the removal of old mitochondria is called mitophagy, and the removal of damaged lipids is called lipophagy.
In general, autophagy exists to:
- recycle and reuse old cell parts,
- destroy bacteria and viruses that are attacking the cell,
- get rid of non-usable cell parts.
How does autophagy happen?
Autophagy is carried on by many cell components, but primarily by autophagy-related proteins (ARPs), autophagosomes, and lysosomes. ARPs signal for the autophagosomes to form, and when they form, they carry the cell debris over to lysosomes.
Lysosomes are specific cell organelles that contain lysing enzymes, which can degrade almost anything, from faulty DNA to damaged proteins and lipids. Once the big structures have been degraded to components, cells can use those components as new building blocks or as food.
Autophagy increases under some specific conditions, like:
- infections by bacteria, viruses or other pathogens,
- prolonged hunger or starvation,
- cell damage.
If for some reason autophagy doesn't work anymore or it slows down, damaged cell parts which can't be removed anymore could cause problems for the cell. This could lead to cells not functioning well anymore, and accumulate damage to DNA and other important parts.
Does autophagy increase lifespan?
Studies done on animals like flies, worms, fish, rats, and mice, tell us that autophagy is increased in long-living organisms. When scientists increased autophagy in those lab animals on purpose, they discovered that the animals lived longer, were getting less sick, and overall had a much healthier and longer life.
Here is how autophagy contributes to longevity:
- it removes damaged and potentially dangerous cell parts,
- helps cells to maintain healthy and functional,
- prevents age-related diseases,
- offers a source of food in times of starvation or prolonged hunger,
- takes part in balancing cellular energy, especially under increased stress.
Unfortunately, as is the case with many cellular processes, autophagy decreases with age. That doesn't mean that our cells stop clearing out damaged parts, but they do so a bit slower. That also means that waste products and damaged cell parts stay in the cells a bit longer and can cause trouble.
A faulty or decreased process of autophagy has also been detected in the development of many diseases, such as:
- Alzheimer's disease,
- Huntington's disease,
- Parkinson's disease,
- Chron's disease,
- Diabetes.
Inducing autophagy, especially as we age, might be beneficial to prolonging our health and lifespan (1).
Some other molecular processes and pathways have been linked to longevity, such as the mTOR and the AMPK pathways. You can read more about them here: Are AMPK and mTOR pathways the molecular key to longevity?
Autophagy and longevity in humans
When it comes to autophagy and anti-aging in humans, there aren't as many scientific studies as those performed on lab animals. The reason is mostly that it's very difficult to induce autophagy in the way it's induced in animal subjects.
However, there are multiple substances (or rather functional dietary supplements) that were scientifically proven to induce autophagy. In some cases, those were also used in human studies to induce and follow the effects of autophagy through time.
Here are the supplements and substances that induce autophagy:
- spermidine,
- resveratrol,
- curcumin,
- urolithin A,
- tomatidine.
Out of these, spermidine and resveratrol were tested in human clinical studies.
Autophagy - studies in humans
Spermidine has been long known and proven as an autophagy inductor, especially in yeast, flies, worms, and mice. This naturally occurring polyamine has then also been tested in a grand human clinical study on more than 800 participants.
The so-called Bruneck study has tested the effects of spermidine on human health and mortality for over 20 years. It was shown that an increase of spermidine in the diet increases human longevity. All-cause mortality (deaths per 1000 person during the tested years) decreased (with increasing spermidine intake) from 40.5 to 15.1 (2).
In this study, spermidine was not administered as a supplement, but increased through a dietary change. The average dietary spermidine intake was 10.8 mg/day in the highest spermidine consumption group. The usual administered and safe doses of spermidine supplements are 6-10 mg per day (3).
There is currently no research on resveratrol-inducing autophagy in humans, only in animals. However, it's already known that resveratrol activates the human Sirt-1 (sirtuin) pathway (4), which is connected to longevity and age-related diseases.
You can read more about resveratrol in our articles:
- How Much Trans-Resveratrol Should I Take?
- Why Is Resveratrol Important?
- Where Does Resveratrol Come From?
Autophagy - fasting
One of the ways of enhancing autophagy for longevity is to practice (intermittent) fasting. When your body has nothing to eat, it will go through a prolonged hunger period and eventually start to eat itself by performing autophagy.
Think of it as living in a house made out of functional food supplies. You normally wouldn't eat any of your walls or ceilings, but if you were hungry for a while, you would start eating them too. You would, of course, first start with the damaged non-functional things you don't need.
Another way to induce autophagy is to exercise. This is partly due to increased inflammation, and partly because there is a lot of evidence that exercising induces autophagy in skeletal muscles (5).
How long should a person stay in autophagy?
Scientific studies done on mice showed that autophagy increases after about 24 hours of fasting. Autophagy is noticed by a drop in insulin and glucose levels in the blood, and in mice, it peaks after 48 hours of fasting.
The studies on humans are still missing, but it is presumed it happens around the same time as it does for mice.
Autophagy - side effects and risks
Autophagy is obviously a normal and natural process that occurs in our organism constantly. Inducing this process might be good for all the reasons already named above, but it also might have some negative side effects.
Overly inducing autophagy might lead to (6):
- developing heart problems,
- slowing cancer therapy, if you're under treatment.
The research on the induction of autophagy and cancer is still unclear. In some cases, the opposite, the inhibition of autophagy, actually might help fight cancer. In other cases, not.
Autophagy is not just a recent trend in the world of health and fitness. It is a normal process that occurs and will occur in every cell of our body every day. It certainly is not a straightforward process and isn't easy to understand as it involves many components.
While pushing autophagy by fasting may be a good option for your health, it may not be for everyone. Before you begin to do so, talk to your doctor, especially if you are pregnant, breastfeeding, or on any medication.
Literature sources:
- Nakamura S, Yoshimori T. Autophagy and Longevity. Mol Cells. 2018 Jan 31;41(1):65-72. doi: 10.14348/molcells.2018.2333.
- Kiechl S, Pechlaner R, Willeit P, Notdurfter M, Paulweber B, Willeit K, Werner P, Ruckenstuhl C, Iglseder B, Weger S, Mairhofer B, Gartner M, Kedenko L, Chmelikova M, Stekovic S, Stuppner H, Oberhollenzer F, Kroemer G, Mayr M, Eisenberg T, Tilg H, Madeo F, Willeit J. Higher spermidine intake is linked to lower mortality: a prospective population-based study. Am J Clin Nutr. 2018 Aug 1;108(2):371-380. doi: 10.1093/ajcn/nqy102.
- Senekowitsch S, Wietkamp E, Grimm M, Schmelter F, Schick P, Kordowski A, Sina C, Otzen H, Weitschies W, Smollich M. High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study. Nutrients. 2023 Apr 12;15(8):1852. doi: 10.3390/nu15081852.
- Hou X, Rooklin D, Fang H, Zhang Y. Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation. Sci Rep. 2016 Nov 30;6:38186. doi: 10.1038/srep38186.
- Brandt N, Gunnarsson TP, Bangsbo J, Pilegaard H. Exercise and exercise training-induced increase in autophagy markers in human skeletal muscle. Physiol Rep. 2018 Apr;6(7):e13651. doi: 10.14814/phy2.13651.
- Schiattarella GG, Hill JA. Therapeutic targeting of autophagy in cardiovascular disease. J Mol Cell Cardiol. 2016 Jun;95:86-93. doi: 10.1016/j.yjmcc.2015.11.019.
