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Autophagy

Also called: Macroautophagy, Self-eating

Written by Reviewed Sep 2026

The cell's recycling system. Worn-out parts get wrapped up, carried to the cell's digestion sac, and broken down into pieces the cell can use again.

What it is

Autophagy is how a cell takes out its own trash and reuses it. A thin double skin forms around the junk and closes into a bag. The bag then joins with a lysosome, which is the cell's acid-filled digestion sac. The junk is broken down into protein building blocks, fats and sugars, and the cell uses them again.

It runs all the time, at a low level, in every cell you have. Fasting does not switch it on from zero. What changes when food runs short is the speed.

Yoshinori Ohsumi won the 2016 Nobel Prize in medicine for working out the genes behind this process. He did that work in yeast, and that is where nearly all the parts were first found.

How it works

The first step is run by a protein called ULK1. It gets the wrapping skin started. ULK1 takes orders from the cell's two main food sensors. When food is plentiful, a sensor called mTORC1 tags ULK1 to hold it back. When energy is short, a sensor called AMPK tags it in other spots to switch it on.

So when mTORC1 goes quiet, the brake comes off. When AMPK rises, it presses the gas. Both happen when you stop eating.

The growing skin is dotted with a protein called LC3. It starts out loose inside the cell as LC3-I. A fat tag gets added, and it becomes LC3-II, which sticks into the wall of the bag. LC3-II is the marker almost every study measures, because the amount of it follows the number of bags in the cell.

p62, also called SQSTM1, is a pickup protein. It grabs tagged trash, hooks onto LC3, and gets destroyed along with the trash. So when p62 goes down, researchers usually read that as autophagy running.

What switches it on

Three things switch it on: falling insulin, falling protein building blocks in the blood (leucine most of all), and the cell running low on ready energy. Each one pushes on a different part of the same control switch.

Exercise raises the same signals, so it is a fair thing to compare with fasting. Some of the clearest measurements of autophagy in people come from exercise studies, not fasting studies.

On the timing
No checked study in people puts a clock hour on when autophagy starts. What has been measured in people is which way it moves after a set time without food, in a set tissue. Those results disagree depending on which tissue is sampled. Blood cells and muscle do not tell the same story. That is the most useful thing to know about this research, and the thing most often left out.

What has been measured

In people

Autophagy has been measured in living people many times. Some studies measured the true speed of the recycling, not just a snapshot of how much is there. The results are real, small, and depend on the tissue. To read them, you need to know which studies measured a speed and which measured a snapshot.

  • The biggest study: 121 people with obesity were split into three groups for six months. One got standard care, one cut calories, and one fasted on some days and also ate inside a set time window. The study measured the real speed of recycling, not just a count of the bags. At six months, the fasting group differed from the standard care group. The calorie-cutting group did not. That difference only showed up in a later look at the data. The authors say it may be partly because autophagy fell in the standard care group. Autophagy did not clearly rise within the fasting group itself (Journal of Physiology, 2025).
  • 50 women fasted for 24 hours, three days a week, for eight weeks. Thigh muscle samples were taken after both 12 and 24 hour fasts. The 24 hour fast raised SQSTM1 (p62). In the group eating fewer calories, the gene signals for BECLIN1, SQSTM1 and LAMP2 fell after an overnight fast. The authors concluded that autophagy markers in human muscle went down (Nutrition, 2022). Read that next to the warning at the end of this list. A falling marker is not the same as falling autophagy.
  • In a four-day study, 11 overweight adults tried two eating windows: 8am to 2pm, and 8am to 8pm. Each person tried both. The early window raised the activity of the autophagy gene LC3A and the ageing-linked gene SIRT1 in blood cells in the morning, before breakfast. It also raised MTOR gene activity in the evening (Nutrients, 2019).
  • 8 healthy men fasted for 72 hours and gave muscle samples. mTOR activity fell by about half. The proteins it controls, 4EBP1, rpS6 and ULK1, were also less active. ULK1 is the protein that starts the recycling process (PLoS One, 2014).
  • Muscle autophagy after a 36 hour fast has been compared between trained and untrained people (Journal of Applied Physiology, 2018).
  • The warning about measurement, and the most important point on this page. In human muscle, the marker LC3B-II fell 24% right after exercise. The same team then tested that same muscle tissue in a dish to see how fast the recycling was really running. It was not falling at all. Their results pointed to a modest to large RISE in recycling speed that lasted up to 24 hours. Their conclusion is that a drop in LC3B-II after exercise does not show the recycling speed. So a study saying muscle autophagy markers went down in people has not shown that autophagy went down (International Journal of Molecular Sciences, 2022).

In animals and in cells in a dish

The process was worked out in yeast. It has been studied in far more detail in mice than in people. That includes organs, like the liver, that are very hard to sample in a living person.

  • In mice, fasting on some days raised autophagy markers in the liver (LC3-I protein and Map1lc3b gene activity). That held on both normal chow and a high-fat diet. On chow, it also raised LAMP1 protein and Beclin1 gene activity in the liver. Mouse muscle showed no switch-on. This mouse work was part of the same 2022 study that tested muscle in 50 women. The liver is where fasting's effect on autophagy is clearest. It is also the organ nobody samples in a healthy volunteer.
  • In rats, the exercise test from the warning in the people column moved the markers the other way. LC3B-I rose 109% and LC3B-II rose 97% (International Journal of Molecular Sciences, 2022).
  • In yeast (Saccharomyces cerevisiae, a single-celled fungus), scientists found nearly all the autophagy genes and the core parts. That work won the 2016 Nobel Prize.

Why it matters

Failing autophagy is one of the known signs of biological ageing. It is also tied to diseases of the brain and nerves, where clumps of protein build up because they never get cleared. That is why it is worth asking whether a normal person can raise it on purpose.

The honest answer so far: one six-month study in 121 people found the recycling speed higher in a fasting group than in a standard care group. That is the strongest result in people, and it is a real finding. But it came from a single later look at the data. Autophagy did not clearly rise within the fasting group itself. And it was measured in blood cells, not in the brain or liver.

A claim you will see repeated

You will see a set hour quoted as the moment autophagy switches on, most often 16 hours. We traced that number through the eight people most often credited with it, reading what they actually wrote and said. Not one of the four researchers closest to the autophagy research gives 16 hours. Valter Longo says about five days, and calls out the short-fast version directly. Peter Attia says it cannot be measured in people at all right now. Satchin Panda names it as an open question and does not answer it. Rhonda Patrick put the 16 hour question to autophagy researcher Guido Kroemer. His answer began "We don't know," and he said his own white blood cell work needed three to four days. Jason Fung gives no number anywhere in his written work. Mark Mattson's much-quoted 16 to 18 hours, in the New England Journal of Medicine, is advice on how to ease a patient into a fasting schedule. In that paper, his hour figures are about ketones, never about autophagy. The number seems to start in a 2018 popular book. There, the sentence "Research shows that 16 hours is optimal" has no source. The reference after it is a study of 4 day and 5 day fasting-mimicking diet cycles, and that study has no 16 hour group at all. The most-cited paper on short fasts and autophagy, Alirezaei 2010, is a study in mice that tested 24 and 48 hours. The closest study in people, Jamshed 2019, used an 18 hour fast in 11 people and measured one gene.

Sources

  1. Study in people2025
    Intermittent time-restricted eating may increase autophagic flux in humans: an exploratory analysis

    The Journal of Physiology

    121 people with obesity were put into one of three groups for 6 months: standard care, eating fewer calories, or fasting on some days plus eating inside a time window. The study measured how fast blood cells were recycling, not just a snapshot. The fasting group changed differently from the standard care group, but only in a later look at the data. The calorie group did not differ. Recycling did not clearly rise within the fasting group itself.

    121 people with obesity randomised for 6 months to standard care, calorie restriction, or intermittent fasting plus time-restricted eating. LC3B-II flux in peripheral blood mononuclear cells within whole blood, a rate measurement rather than a static marker. Significant difference in change from baseline between the fasting arm and standard care at 6 months (P = 0.04, post hoc); calorie restriction versus standard care not significant; no significant change from baseline within the fasting arm.

  2. Study in people2019
    Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans

    Nutrients

    11 overweight adults each tried two eating windows for 4 days: 8am to 2pm and 8am to 8pm. The early window raised an autophagy gene (LC3A) and SIRT1 in blood cells before breakfast. It also raised the MTOR gene in the evening. Average blood sugar over 24 hours was 4 mg/dL lower, and blood sugar swings were 12 mg/dL smaller.

    11 overweight adults, 4-day randomised crossover of an 8am to 2pm window versus 8am to 8pm. The early window raised whole blood cell expression of the autophagy gene LC3A and of SIRT1 before breakfast (p < 0.04), raised MTOR expression in the evening (p = 0.007), and lowered mean 24-hour glucose by 4 mg/dL and glycaemic excursions by 12 mg/dL.

  3. Study in people2022
    Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans

    Nutrition

    50 women, average age 51, fasted for 24 hours on 3 days a week for 8 weeks. Some ate 70% of their calorie needs and some ate 100%. Thigh muscle samples were taken after 12 and 24 hour fasts. A 24 hour fast raised one recycling marker (SQSTM1). In the 70% group, three recycling gene signals fell after an overnight fast. Overall, recycling markers in their muscle went down. The authors put that down to weight loss.

    50 women, mean age 51, randomised to intermittent fasting (24-hour fast on 3 non-consecutive days per week) at 70% or 100% of energy requirements for 8 weeks, with vastus lateralis biopsies after 12 and 24 hour fasts. A 24 hour fast raised SQSTM1; BECLIN1, SQSTM1 and LAMP2 mRNA fell in the 70% arm after an overnight fast. Autophagy markers in human muscle were reduced, the authors attribute this to weight loss.

  4. Study in people2014
    Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling

    PLoS One

    8 healthy men gave muscle samples after an overnight fast and again after a 72 hour fast. After 72 hours, the growth switch mTOR was about 50% less active. So were the proteins it controls, including ULK1, the protein that starts the cell's recycling.

    8 healthy men studied postabsorptive and after a 72 hour fast, with forearm amino acid tracer kinetics and muscle biopsies. mTOR phosphorylation fell about 50%, with reduced downstream phosphorylation of 4EBP1, rpS6 and ULK1, the kinase that starts autophagosome formation.

  5. Study in people2022
    Exercise and Training Regulation of Autophagy Markers in Human and Rat Skeletal Muscle

    International Journal of Molecular Sciences

    In human muscle, the recycling marker LC3B-II fell 24% right after exercise and was back to normal by 3.5 hours. Tests on that same muscle in a dish showed recycling was not slowing. It looked to be speeding up, modestly to strongly, for up to 24 hours. So a falling marker does not mean falling recycling. In rats, the same exercise raised the markers 109% and 97%, the opposite direction.

    The keystone methodological result. In human skeletal muscle LC3B-II protein fell 24% immediately after exercise and returned to baseline by 3.5 hours, while in rat soleus the same protocol raised LC3B-I 109% and LC3B-II 97%. An ex vivo flux assay on the human tissue showed the fall did NOT reflect reduced flux: effect sizes indicated a modest to large increase in autophagy flux lasting up to 24 hours. The authors conclude that exercise-induced decreases in LC3B-II do not reflect autophagy flux level, and that rodents and humans move these markers in opposite directions.

  6. Study in people2018
    Training state and skeletal muscle autophagy in response to 36 h of fasting

    Journal of Applied Physiology

    Researchers looked at muscle recycling markers during a 36 hour fast and compared people with different training levels. This entry does not say what they found.

    Human skeletal muscle autophagy markers compared between training states across a 36 hour fast.