MOTS-c
MOTS-c is a highly advanced mitochondrial-derived peptide (MDP) literally encoded within the mitochondrial genome rather than the cell nucleus. Dubbed an "exercise mimetic," it is deployed in precision metabolic protocols to systemically reverse age-related insulin resistance and crush metabolic syndrome. By supercharging cellular bioenergetics, it dramatically enhances fatty acid oxidation, fundamentally shifting the body from glucose dependency to profound fat-burning, even in a sedentary state.
Quick Stats
Scientific Data
Mechanism of Action
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a mitochondrial-derived peptide (MDP) — a signaling molecule encoded in the mitochondrial genome rather than the nuclear genome. It activates the AMPK pathway, the master metabolic regulator that enhances cellular energy metabolism, improves insulin sensitivity, and promotes glucose uptake in skeletal muscle.
MOTS-c represents a new class of signaling molecules called "mitokines" — mitochondrial hormones that communicate metabolic status from mitochondria to the nucleus and distant tissues. It has shown exercise-mimetic effects, improving metabolic health and physical performance in animal models.
Source: PMID: 25738459
Background & History
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene, discovered by Changhan David Lee at USC in 2015 (Cell Metabolism). It was the first regulatory peptide found to be encoded in mitochondrial DNA rather than nuclear DNA — a paradigm shift in mitochondrial biology. MOTS-c acts as a retrograde signal from mitochondria to the nucleus, activating AMPK and regulating metabolic gene expression. Exercise increases circulating MOTS-c levels, suggesting it mediates some of the metabolic benefits of physical activity.
Research Use Cases
- ✓Metabolic health and insulin sensitization
- ✓Exercise performance enhancement via AMPK activation
- ✓Obesity and type 2 diabetes research protocols
- ✓Skeletal muscle function and age-related metabolic decline
- ✓Longevity: mitochondrial health and lifespan extension (preclinical)
Dosing Protocol
| Typical Dose | 5-10 mg/week |
| Frequency | 3-5× weekly |
| Half-Life | ~4-6 hours (estimated) |
| Common Vial Sizes | 5 mg, 10 mg |
Dosing Protocols
Standard Protocol
Body-Weight Dosing Reference
Estimated doses extrapolated from the published research range of 5000–10000 mcg/day (referenced to 70 kg / 154 lb). These are approximations — consult a qualified healthcare provider for personalised guidance.
| Weight | Low Dose | Target Dose | High Dose |
|---|---|---|---|
| 120 lb(54 kg) | 3857 mcg | 5786 mcg | 7714 mcg |
| 140 lb(63 kg) | 4500 mcg | 6750 mcg | 9000 mcg |
| 160 lb(73 kg) | 5214 mcg | 7821 mcg | 10429 mcg |
| 180 lb(82 kg) | 5857 mcg | 8786 mcg | 11714 mcg |
| 200 lb(91 kg) | 6500 mcg | 9750 mcg | 13000 mcg |
| 220 lb(100 kg) | 7143 mcg | 10714 mcg | 14286 mcg |
| 250 lb(113 kg) | 8071 mcg | 12107 mcg | 16143 mcg |
💉 For exact syringe units based on your vial concentration, use the MOTS-c Reconstitution Calculator →
Administration
Expected Timeline
Who Is It For?
Metabolic Optimization
ModerateAMPK activation improves glucose metabolism and insulin sensitivity. Exercise-mimetic properties.
Longevity / Anti-Aging
LowPromising mitokine signaling in animal models. Human data is very limited.
Reconstitution Example
Safety & Considerations
Research peptide. Limited human safety data — primarily rodent models. Naturally occurring endogenous mitochondrial peptide. Monitor blood glucose if diabetic.
Regulatory & Legal Status
Not currently on the WADA 2026 Prohibited List. Policies may change — verify before competition.
Research Chemical
US Compounding: Not eligible / not available
⚠️ This information is for educational purposes only and may not reflect the most current regulatory updates. Always verify with official FDA, WADA, and jurisdiction-specific sources before use.
Interactions & Contraindications
Research compound — limited human safety data. AMPK activation may interact with metformin (additive effects on glucose metabolism). Caution with insulin or GLP-1 agonists due to additive insulin sensitization. Available in injectable form; oral bioavailability very limited.
Synergies & Common Stacks
Both are mitochondrial-derived peptides (MDPs) with overlapping cytoprotective effects. Humanin protects against apoptosis; MOTS-c enhances metabolic function. Often combined in mitochondrial health protocols.
NAD+ fuels mitochondrial function; MOTS-c activates the AMPK pathway downstream. Together they support comprehensive mitochondrial bioenergetics and metabolic resilience.
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Dosing Quick Reference
Frequently Asked Questions
What does MOTS-c do?▼
How is MOTS-c dosed?▼
References
- Reynolds JC et al. “"MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline".” Nature Communications (2021). PMID: 33594076
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