MOTS-c is a short peptide that the body makes from a gene inside the mitochondria, the structures that produce most of a cell’s energy, and almost everything known about taking it comes from mice. The human evidence so far consists of measuring the MOTS-c people already produce, which is a different question from whether giving more of it does anything. On this site it sits under the longevity goal as a research-only compound.
Where MOTS-c came from
The peptide was described in 2015 by a group that searched mitochondrial DNA for short stretches able to encode signaling molecules [1]. They found a 16-amino-acid peptide encoded within the gene for the 12S ribosomal RNA and named it MOTS-c, for mitochondrial open reading frame of the 12S rRNA-c. Its main target appeared to be skeletal muscle.
The proposed mechanism runs in three steps. Inside the cell, MOTS-c inhibits the folate cycle and the purine synthesis tied to it. That shift activates AMPK, an enzyme that acts as a fuel gauge and pushes cells toward burning glucose and fat. In the 2015 mouse experiments, treatment prevented insulin resistance that came with age or a high-fat diet, and prevented diet-induced obesity [1]. That chain is well described in mice, and it is still a hypothesis in people.
The exercise study, and what it did and did not test
A 2021 paper extended the work to aging and physical capacity [2]. In mice, treatment improved running performance at young, middle and old ages. Old mice given MOTS-c daily for two weeks, at 15 mg/kg by intraperitoneal injection, ran 2-fold longer than untreated old mice. Treatment started late in life, three times a week, also improved physical capacity.
The same paper included the only human data on MOTS-c function so far. Ten sedentary, healthy young men did an interval session on a stationary bike, with muscle biopsies and blood draws before and after (n = 10). MOTS-c in their muscle rose 11.9-fold after exercise, and circulating levels rose about 1.5-fold, returning to baseline within four hours of rest.
Two authors of that paper, including the scientist who first described MOTS-c, declared that they consult for and hold shares in a biotech company [2]. That company sponsored an analog of MOTS-c, called CB4211, in a phase 1 study of 88 people that completed in 2021 [3]. The registry lists no posted results, and an analog is a different molecule, so that study cannot stand in for MOTS-c itself.
What regulators say
The FDA reviewed MOTS-c when it was nominated for use in compounding. Its summary states that compounded MOTS-c may pose a significant risk of immunogenicity for certain routes and may have complexities with peptide-related impurities [4]. It adds that the agency has not identified any human exposure data for MOTS-c given by any route. The May 2026 list of 503A categories does not include it in any category [5], which is why this site treats it as research-only.
On July 23, 2026, the FDA’s Pharmacy Compounding Advisory Committee discussed MOTS-c for the 503A bulks list [8]. The FDA’s own briefing document concluded that the balance of criteria weighs against listing it, finding the substance not well characterized [9]. The committee voted 7–5 to recommend listing it anyway, with two abstentions [10]. The vote does not bind the FDA, and a listing would still need notice-and-comment rulemaking, so MOTS-c remains on no list.
A 2026 review of peptides marketed directly to patients places MOTS-c among the unapproved compounds whose favorable animal results have no rigorous human safety data behind them [6].
The first placebo-controlled trial
A randomized, double-blind phase 2a trial registered in 2026 plans to enroll 120 adults with prediabetes and overweight or obesity [7]. Participants receive a fixed daily subcutaneous dose or placebo for 12 weeks. The primary outcomes are a change in insulin sensitivity on an oral glucose tolerance test and the rate of adverse events. It was recruiting at its last update, with primary completion estimated for February 2027. When it reports, it will be the first human efficacy data on MOTS-c itself.
MOTS-c is often grouped with other energy-metabolism compounds; the human evidence for one of them, taken by a different route, is covered in what is known about NAD nasal spray. For the same pattern of strong animal data and missing human trials in a recovery peptide, see the human evidence for BPC-157. The way this site separates animal from human findings is set out in the methodology.