MOTS-c

Not FDA-approved

Also known as: Mitochondrial open reading frame of the 12S rRNA-c

MOTS-c is a peptide of 16 amino acids that the body makes from DNA inside mitochondria, the cell's energy-making parts. In mice, it improved insulin sensitivity and physical performance. No trial of MOTS-c itself has reported results in people; the only completed human trial used a modified version.

How it works

It is coded by a short stretch of the mitochondria's own DNA, inside the 12S rRNA gene, rather than by DNA in the cell nucleus.
In mouse and cell studies, it acts mainly on muscle. It slows the folate cycle, a chemical pathway, which switches on AMPK, an energy sensor that exercise also activates.
In cell-free lab tests, it binds and activates an enzyme called CK2. In mice, blocking CK2 blunted its effects on muscle sugar uptake and muscle wasting.
In a small study of young men, intense exercise raised the body's own MOTS-c levels in muscle and in the blood.
In a genetic study of over 27,000 people of Japanese ancestry, men with a less active form of MOTS-c had more type 2 diabetes. In one group, this was seen only in the least active men.

Evidence

Insulin resistance and weight gain

Animal and lab studies onlyCEBM Level 5

In mice on a high-fat diet, MOTS-c injections prevented insulin resistance and weight gain. It also prevented the insulin resistance that develops with age in mice. No trial of MOTS-c itself has reported results in people.

Physical fitness with aging

Animal and lab studies onlyCEBM Level 5

In young, middle-aged and old mice, it improved physical performance. Treatment started late in life improved physical capacity in old mice. This has not been tested in people.

Caveats

No completed clinical trial has tested MOTS-c itself. The only completed human trial, an early safety study, used CB4211, a modified lab-made version. A first placebo-controlled trial of MOTS-c itself, in prediabetes, began in 2026.
In lab tests, human blood broke MOTS-c down quickly into shorter pieces. Whether an injection under the skin reaches active levels in people has not been studied.
No formal animal safety (toxicology) studies have been published, and there are no human safety data for MOTS-c itself.
Published studies in people have only measured the MOTS-c the body makes naturally. Those links do not show that taking it as a treatment helps.
There are no human safety data in pregnancy.

References

Reviewed by Shubham Gupta, MD — Founder & President · October 31, 2026

This page is for education only. It is not medical advice. Decisions about any treatment belong with a physician who knows your history.