MOTS-c
Also known as: Mitochondrial Open Reading Frame of the 12S rRNA-c, Mitochondrial Derived Peptide
Overview
MOTS-c is a 16-amino acid mitochondrial-derived peptide (MDP) encoded by a short open reading frame within the 12S rRNA gene of mitochondrial DNA. It is one of the most recently discovered endogenous peptide hormones, identified in 2015, and functions as a regulator of metabolic homeostasis and aging. Plasma MOTS-c levels decline ~21% by ages 70-81 compared to young adults, and exogenous MOTS-c treatment has demonstrated remarkable metabolic rescue effects in aging and obese models including prevention of diet-induced and age-related insulin resistance.
Mechanism of Action
MOTS-c translocates to the nucleus under metabolic stress, where it acts as a nuclear regulatory peptide influencing gene expression related to metabolism and stress response. Key mechanisms include: AMPK pathway activation driving metabolic flexibility; elevation of intracellular NAD+ levels through effects on the folate/methionine cycle; SIRT1 activation mediating glycolytic effects; restriction of methionine metabolism (methionine restriction extends mouse lifespan by 45%); reduction of IL-6-driven MMP1 in skin improving collagen retention; and enhancement of physical performance and insulin-sensitive tissue function.
Potential Benefits
- Prevention and reversal of diet-induced obesity and insulin resistance
- Prevention of postmenopausal obesity and metabolic syndrome
- Improved physical performance across all age groups in animal models
- Elevated NAD+ levels supporting cellular energy and longevity
- AMPK activation mimicking exercise benefits metabolically
- Cardiovascular disease risk reduction in aging models
- Skin collagen preservation via IL-6/MMP1 reduction
- Potential Alzheimer's disease and osteoporosis protection
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Typical Range | 5-10 mg/week |
| Beginner | 5 mg once weekly |
| Intermediate | 5-10 mg twice weekly |
| Advanced | 10 mg 2-3x/week |
| Cycle Duration | 4-8 weeks |
| Cycle Off | 4 weeks |
MOTS-c is mitochondria-derived and endogenously increases with exercise. Exogenous administration mimics exercise-induced metabolic adaptation. Best combined with physical exercise for synergistic metabolic benefits.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Subcutaneous Injection High — systemic metabolic effects
Standard method. Typical dose 5–10 mg, 3–5x per week. Best administered 30–60 min before exercise.
Intramuscular Injection High — direct muscle delivery
Alternative method. May provide faster onset of metabolic effects in target muscle tissue.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving MOTS-c:
Metabolic Optimization Stack
Comprehensive metabolic support. MOTS-C for AMPK activation and insulin sensitivity, AOD-9604 for targeted fat metabolism, Semaglutide for appetite regulation and GLP-1 signaling.
Performance Stack
Athletic recovery and metabolic performance. MOTS-C enhances exercise capacity and mitochondrial function, BPC-157/TB-500 accelerate tissue repair.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Typical Vial Size | 5mg, 10mg |
|---|---|
| BAC Water | 1-2ml per 5mg vial |
| Storage | Refrigerate at 2-8°C after reconstitution |
| Shelf Life | 28 days refrigerated |
Need exact syringe measurements?
Amino Acid Sequence
MRWQEMGYIFYPRKLR (16 amino acids)
Side Effects & Safety
- Minimal known side effects in rodent studies
- Limited human safety data
- Injection site reactions with subcutaneous use
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Pregnancy / Lactation
Bleeding Disorders
Active Skin Infection at Injection Site
FDA Safety Information
FDA Category 2 concerns: significant immunogenicity risk, no human exposure data.
Pharmacokinetics
| Half-Life | ~30 minutes - 1 hour (plasma) |
|---|---|
| Storage | Store lyophilized peptide at -20°C (long-term) or 2-8°C (short-term, under 30 days). Reconstituted: refrigerate at 2-8°C and use within 28-30 days. Protect from light. Do not freeze reconstituted solution. |
Synergistic Compounds
The following compounds have been studied alongside MOTS-c for potential complementary or synergistic effects:
Learn More
References & Further Reading
- MOTS-c Mitochondrial Derived Peptide - International Journal of Molecular Sciences PMC
- MOTS-c Player in Aging - PubMed
- MOTS-c Expression with Aging - Aging
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
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