MOTS-c

MOTS-c is a chain of 16 amino acids, the small building blocks that proteins are made from, and short chains like this are called peptides. What is unusual about it is where the instructions for building it are kept. They sit in a separate set of DNA, the one carried by mitochondria, the compartments in a cell that turn food into usable energy, and they hide inside a gene understood to do something else entirely, readable only if you start at a different point, like a recipe that also spells out a note to somebody else in the house if you begin at a different letter. It was named in a 2015 paper in the journal Cell Metabolism by Lee, Zeng, Drew and colleagues at the University of Southern California, who reported that the muscle you move with is its main target. No published or properly registered study has ever given it to a human being, so everything known about taking it comes from mice.

Nobody knows what it latches onto. No receptor for MOTS-c has been identified, meaning the docking point on a cell that a substance has to attach to in order to do anything has never been found, so nobody knows the target it acts on. The route people propose is an indirect one: it is said to block the folate cycle, one of the cell's small chemical assembly lines, which lets a substance called AICAR build up, and that in turn switches on AMPK, the enzyme that works as the cell's fuel gauge. None of that has been shown to happen in a person who was injected with it.

This entry does not survey what buyers say they are after, so what follows is the set of claims in circulation and where each one came from. The mouse work is about endurance and physical function: 12 month old mice and 22 month old mice both ran about twice as long as untreated mice their own age, and a group started at about 24 months, too old to run, improved on grip strength, stride length and a 60 second walking test. A separate mouse arm on a fattening diet resisted weight gain. The fabricated registry record advertises better handling of blood sugar in people on the edge of diabetes, and peptide blogs cite that record as an ongoing human trial.

The costly mistake is reading a measurement as a trial. In the 2021 paper, ten sedentary young men, average age about 24, rode a stationary bicycle to exhaustion, and the amount of MOTS-c their own bodies were already making rose 11.9 fold in muscle and 1.5 fold in blood, returning to normal within four hours. The men received no peptide at all. Measuring how much of a substance is already inside somebody is a completely different kind of evidence from giving it to them and watching what happens, and that study is routinely sold as a human trial of the injection. The same error runs the other way with CB4211, the modified version tested in the one completed trial, whose final group of 20 obese people with fatty liver got 25 mg once daily for four weeks, which is 2.5 to 5 times the amount people inject of a molecule that is not the same thing.

There is nothing to report from a person given MOTS-c, because no published study has given it to one, so the empty record means untested rather than clean. The nearest thing is the completed trial of CB4211, the modified version, where the sponsor announced no serious adverse events along with improvements in two liver enzymes and in blood sugar, but announced it in a press release rather than in a scientific paper, which is a different standard of evidence. Reactions at the injection site are common across this class of compound and are a consequence of injecting.