16AA Animal Models
MOTS-C
Mitochondrial exercise mimetic — a 16AA peptide encoded by mitochondrial DNA that activates AMPK and mimics the molecular signature of endurance exercise.
In Plain English: MOTS-C is a tiny protein your mitochondria naturally produce to tell cells to burn fat, absorb glucose, and behave like they just finished a workout. Levels drop sharply with age. In animals, supplementing it restores the metabolic profile of youth — better insulin sensitivity, more endurance, less fat gain — without requiring exercise.
Research Maturity
Animal Models (233 results on PubMed for 'MOTS-c' (verified 2026-05-04)+ Studies)
Quick Facts
Focus
Exercise Performance
Healthy Aging
Metabolic Health
Route
SubQ
Origin
Discovered 2015 by Lee et al. at USC. Uniquely encoded by the mitochondrial genome within MT-RNR1 (12S rRNA) gene — the only known peptide hormone with this origin. Endogenous levels rise 11.9-fold during acute aerobic exercise and decline with age.
Mechanism
Inhibits folate-cycle enzyme MTHFD2, secondarily activating AMPK. AMPK triggers: enhanced muscle glucose uptake independent of insulin, upregulated fatty acid oxidation, mTORC1 suppression, and nuclear translocation of MOTS-C itself to bind ARE transcription factors improving mitochondrial stress resistance.
Outcome
Reverses diet-induced insulin resistance and obesity in mice; extends physical capacity in aged mice (2-fold treadmill endurance); prevents beta-cell senescence; protects diabetic heart; suppresses ovarian cancer; reduces neuroinflammation in sepsis models. Human evidence limited to observational correlation between serum levels and lower T2D.
Safety Flags & Warnings
No Human Clinical Trials
Hypoglycaemia Risk with Diabetes Meds
WADA Prohibited (in & out of competition) (S4 Metabolic Modulators)
Pregnancy Contraindication (Folate Cycle)
Active Cancer — Avoid
Always consult a licensed physician. Research purposes only.
€4.5 / mg
