Overview
MOTS-c is a mitochondrial-derived peptide (MDP) encoded within the 12S rRNA gene of mitochondrial DNA. Discovered in 2015 by Changhan David Lee at USC, it is one of the first identified peptides encoded by the mitochondrial genome rather than nuclear DNA. MOTS-c acts as a metabolic regulator, improving glucose metabolism, insulin sensitivity, and exercise capacity. It has been called an 'exercise mimetic' peptide.
Mechanism of action
MOTS-c activates AMPK (AMP-activated protein kinase), the master metabolic sensor that coordinates cellular energy metabolism. It enhances glucose uptake in skeletal muscle, improves insulin sensitivity, promotes fatty acid oxidation, and regulates the folate-methionine cycle affecting cellular methylation. Under metabolic stress, MOTS-c translocates to the nucleus where it regulates adaptive gene expression through interaction with ARE-containing promoters.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| metabolic optimization / exercise mimetic | subcutaneous | 5–10 mg | 3-5x weekly | Inject in the morning or pre-workout. Often combined with exercise protocol. 4-8 week cycles. Limited dosing data — extrapolated from animal studies. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Lee et al. (2015, Cell Metabolism) demonstrated MOTS-c prevents age-dependent and high-fat-diet-induced insulin resistance in mice. Subsequent studies showed improved exercise performance, skeletal muscle metabolism, and weight management. A 2020 study found higher circulating MOTS-c levels in long-lived populations. Human studies show MOTS-c increases during exercise, suggesting it mediates some exercise benefits. Animal lifespan studies show positive trends. Clinical trials are in early stages.
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with MOTS-c for synergistic effects.
Legal status
Not FDA-approved. Available as a research peptide. Relatively new (discovered 2015) with limited regulatory attention.
Where to get it
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