MOTS-c

In simple words

MOTS-c is a peptide produced by the mitochondria themselves; it is called a "mitochondrial hormone," and its levels decline with age. It is studied as "exercise in a molecule" — for improving sugar metabolism and endurance and for protection against age-related metabolic changes.

What this molecule is

MRWQEMGYIFYPRKLR — 16 aa. Encoded by mitochondrial DNA (12S rRNA). ~2174 Da. Discovered in 2015.

Why it is studied

A "mitochondrial hormone." Levels decline with age and in obesity. 2024 RCT: ↑insulin sensitivity, ↑oxidative phosphorylation. ↑Physical endurance. Translocates to the nucleus → transcriptional regulator of metabolism.

How it works

AMPK activation → ↑β-oxidation, ↑autophagy. Nuclear translocation → ↑antioxidant genes (Nrf2). ↓Inflammation (↓NF-κB). ↑Glucose utilization (GLUT4). Analogy: exercise in a molecule.

Doses used in studies

Studies used 10 mg SC twice a week.

Combined with in studies

• Epitalon — anti-aging synergy
• SS-31 — dual mitochondrial support
• GLP-1 agonists — different mechanisms against insulin resistance

Level of evidence

Level B Human observational data. There are studies in humans, but they are small, uncontrolled, or cohort studies. The data are encouraging but need confirmation.

Important to know

Few clinical RCTs; research is actively ongoing. Research only.

Studies in PubMed

1. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. (Front Endocrinol (Lausanne), 2023)
2. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. (Int J Mol Sci, 2022)
3. An 8-Week study on the effects of high and Moderate-Intensity interval exercises on mitochondrial MOTS-C changes and their relation to metabolic markers in male diabetic sand rats. (Diabetes Res Clin Pract, 2024)
4. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. (Diabetes Metab J, 2023)