MOTS-c

Overview and classification

MOTS-c ("mitochondrial open reading frame of the 12S rRNA-c") is a 16-amino-acid peptide encoded in the DNA of mitochondria, the energy structures inside cells. [1] It is a natural, body-made molecule, which is a different thing from a synthetic version sold online or an analogue made by a drug company. For the wider family see Mitochondrial Signaling and Mitochondrial-Derived Peptides and Humanin. Evidence labels used: preclinical (cells/animals only), promising but limited, insufficient evidence, marketing claim, and proper evidence not found.

How it is thought to work

In the first report, MOTS-c acted mainly on skeletal muscle, inhibited the folate cycle and purine building, and activated AMPK, a cellular energy sensor. [1] Under stress it moves into the cell nucleus to change gene activity, and circulating levels are reported to decline with age. [2] Mechanism is not benefit: see Mechanisms vs Demonstrated Clinical Benefits.

What research shows

Mouse studies (preclinical). MOTS-c treatment in mice prevented age-related and high-fat-diet insulin resistance and diet-induced obesity. [1] A later paper reported that MOTS-c enhanced physical performance in young, middle-aged and old mice, and that late-life intermittent treatment increased physical capacity. [3] Two of the authors disclosed being consultants and shareholders of CohBar, a company developing mitochondria-derived drugs. [3] Label: preclinical (cells/animals only).

Human data: natural levels, not treatment. The same paper reported that exercise raises MOTS-c in human muscle and in blood. [3] That shows the body makes MOTS-c; it does not show that injecting it helps.

Human treatment studies. A Phase 1a/1b safety study of a drug candidate called CB4211, sponsored by CohBar, in healthy people and people with fatty liver disease is listed as completed with no results posted. [4] The registry entry does not say how CB4211 relates to MOTS-c, so I do not treat it as evidence about MOTS-c. A Phase 2a trial of MOTS-c in adults with prediabetes and overweight, run by a company, is registered as recruiting, with 120 participants planned for 12 weeks and no results. [5] Registration is not evidence of benefit. Label: insufficient evidence. I found no peer-reviewed randomized trial of MOTS-c itself in the sources searched: Proper evidence not found for improving insulin sensitivity, exercise performance or aging in people.

Confusing items to watch: mouse performance data are not human performance data; higher or lower circulating levels are biomarkers, not outcomes ([2]; see Biomarker Changes vs Meaningful Health Outcomes).

Quality and naming

Sold "research" MOTS-c has no verified identity or sterility from the sources read. See Research Peptide Naming and Identity Problems, Peptide Safety and Sports Anti-Doping Rules for Peptides.