Do proteins inhibit your autophagy?

Proteins inhibit autophagy through one central link: the mTOR protein. Amino acids, the building blocks of proteins, activate mTOR as soon as they enter the cell. An active mTOR puts the brakes on autophagy. This mechanism is well documented in cell studies and animal research, and is the target of drugs such as rapamycin.

How this works in practice: two transport proteins on the cell surface allow amino acids to enter. If you switch off those transport proteins, mTOR is inhibited and autophagy becomes measurably active. In other words: as long as you take in enough protein, mTOR keeps autophagy suppressed. This has been demonstrated in cell culture experiments.

During prolonged fasting, an interesting feedback loop comes into play. Autophagy breaks down old cellular material and in doing so delivers new amino acids. Those amino acids reactivate mTOR, which causes autophagy to switch itself off after a while. So proteins also inhibit autophagy at the end of the cycle. This has been studied in kidney tissue from rats and comparable animal models; direct data in humans are lacking.

In aged cells the picture is more complex. Autophagy can actually be elevated there, even when mTOR is active, via pathways that bypass mTOR. In addition, autophagy in those cells supplies amino acids that feed mTOR, which sustains the production of inflammatory substances. Whether it is then better to inhibit mTOR or not depends strongly on the cell type; the outcome ranges from recovery to cell death.

The key point for you as a reader: a protein-rich meal, or more precisely the amino acids it contains, keeps mTOR active and thereby inhibits autophagy. Fasting or a temporary low protein intake is the most studied way to release that brake. How long or how strict that fasting needs to be has not yet been established in large human studies.