MOTS-c
Mitochondrial Open Reading Frame of the 12S rRNA-c
MOTS-c is a 16-amino acid mitochondrial-derived peptide encoded by the mitochondrial genome. It acts as a mitohormone that regulates metabolic homeostasis, enhances insulin sensitivity, and promotes longevity. MOTS-c operates through the Folate-AICAR-AMPK pathway and can translocate to the nucleus under metabolic stress to regulate gene expression.
Daily dose
5-15mg
Frequency
1x daily or 3x weekly
Cycle length
4-12 weeks
Storage
2-8°C
Key benefits
Enhanced insulin sensitivity, improved glucose metabolism, AMPK pathway activation, mitochondrial function optimization, exercise performance enhancement, and potential longevity benefits.
How it works
MOTS-c operates through the Folate-AICAR-AMPK pathway and translocates to the nucleus under metabolic stress to regulate gene expression involved in metabolism, antioxidant response, and cellular stress adaptation.
Dosage protocols
Goal
Metabolic health
Dose
5-10mg · Once daily
Route
Subcutaneous
Goal
Anti-aging protocol
Dose
15mg · 3x weekly
Route
Subcutaneous
Goal
Exercise performance
Dose
10-15mg · Pre-workout
Route
Subcutaneous
Goal
Conservative start
Dose
5mg · Once daily
Route
Subcutaneous
Research indications
metabolic
anti Aging
exercise
Administration
Interactions
Safety notes
Generally well-tolerated with minimal side effects
Monitor blood glucose if using diabetes medications
Limited long-term human safety data
May cause mild injection site reactions
Not recommended during pregnancy or breastfeeding
WADA prohibited substance for athletes
Research studies
Gestational Diabetes Mellitus (2022)
Mice | Daily administration during pregnancy | Throughout pregnancy | Alleviated hyperglycemia, improved maternal-fetal outcomes
Yin et al. showed MOTS-c significantly alleviated hyperglycemia in GDM mouse model, improved insulin sensitivity, and reduced birth weight abnormalities. Human study found significantly lower serum MOTS-c levels in GDM patients versus controls.
View study →Acute Exercise Enhancement (2022)
Mice & Rats | 15 mg/kg single dose i.v. | Acute administration | 12% increased running time, 15% increased distance
Hyatt et al. showed single dose MOTS-c improved running time by 12% and distance by 15% in untrained mice. Chronic training increased MOTS-c protein expression 1.5-5-fold in muscle tissue, demonstrating both acute and chronic exercise-enhancing effects.
View study →Exercise Performance and Age-Dependent Physical Decline (2021)
Mice & Humans | 15 mg/kg 3x weekly (mice) | Variable duration | Enhanced physical performance across all age groups
Reynolds et al. demonstrated MOTS-c significantly enhanced physical performance in young, middle-aged, and old mice. Exercise induced 11.9-fold increase in skeletal muscle MOTS-c in humans. Acts as mitochondrial-encoded regulator of age-dependent physical performance.
View study →Nuclear Translocation Under Metabolic Stress (2018)
Cell culture & Mice | 1-10 μM in vitro | 30 min-24 hours | Nuclear translocation under stress
Kim et al. demonstrated MOTS-c rapidly translocates to nucleus within 30 minutes of metabolic stress. Once nuclear, it binds to stress-response transcription factors including NRF2 and ATF1/ATF7 to regulate antioxidant and stress-response genes.
View study →Coronary Endothelial Dysfunction (2018)
Human patients (n=40) | Observational study | - | Lower MOTS-c levels correlate with endothelial dysfunction
Qin et al. found MOTS-c plasma levels were significantly lower in patients with endothelial dysfunction. Circulating MOTS-c positively correlated with both microvascular and epicardial coronary endothelial function. First human study linking MOTS-c to cardiovascular health.
View study →Metabolic Homeostasis and Obesity Prevention (2015)
Mice | 0.5-5 mg/kg/day i.p. | 3-8 weeks | Prevented obesity, improved insulin sensitivity by ~30%
Foundational study by Lee et al. demonstrating MOTS-c prevents obesity in high-fat diet-fed mice despite identical caloric intake. Restored insulin sensitivity in aged mice to levels comparable to young animals through the folate-AICAR-AMPK pathway.
View study →