MOTS-C
MOTS-C is a 16-amino acid peptide encoded within the mitochondrial 12S rRNA gene, making it a member of a newly identified class of 'mitochondria-derived peptides' (MDPs) that act as systemic hormones rather than mere metabolic byproducts. In rodent studies it improves insulin sensitivity, reduces diet-induced obesity, and enhances exercise capacity, in part by activating AMPK and the FOXO1 transcription pathway in skeletal muscle. Circulating MOTS-C levels in humans decline with age and correlate with metabolic health markers, suggesting it may play a role in metabolic aging biology. Human interventional studies are essentially absent; all available interventional evidence is preclinical, and no dose, formulation, or long-term safety profile has been characterized for exogenous use.
Evidence last reviewed: 04 Apr 2026
Not a routine supplement — not recommended for self-directed use.
Information here is educational only, not a recommendation to use. See our Safety page.
Evidence is from research or clinical settings — does not imply safety outside supervised contexts.
The evidence for MOTS-C is largely preclinical, with animal studies suggesting improvements in metabolic health and exercise capacity. However, there is a significant gap in human clinical trials, and no established dosing or safety profile exists for exogenous use.
Running performance under metabolic stressMice on high-fat diet (preclinical) · Animal studyLow
In mice, MOTS-c treatment improved treadmill running performance under diet-induced metabolic stress & showed metabolic regulatory effects.
Exercise/metabolic signaling (summary)Mostly preclinical · ReviewVery low
Reviews propose metabolic & stress-response roles primarily based on preclinical evidence; no effective method of applying MOTS-c in the clinic has been established as of 2024-2025.
Clinical translation statusHumans (clinical development commentary) · Review / perspectiveLow
Reviews note that clinical trials to test therapeutic MOTS-c potential are limited/ongoing; overall human efficacy evidence remains early. Blood MOTS-c levels are reported lower in type 2 diabetes & obesity, but therapeutic dosing in humans has not been validated.
Mitochondria-oriented peptide grouping. SS-31 has clinical trials in specific mitochondrial diseases; MOTS-C is mostly preclinical.