MOTS-c
Mitochondrial ORF-derived Peptide
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-C) is a mitochondrial-derived peptide (MDP) that plays a crucial role in metabolic regulation, energy homeostasis, and cellular stress adaptation. Unlike most peptides, which are encoded by nuclear DNA, MOTS-c is produced directly by mitochondrial DNA (mtDNA), allowing it to act as a unique metabolic regulator that responds to cellular energy demands. It primarily functions by activating AMP-activated protein kinase (AMPK), a key enzyme involved in glucose uptake, fatty acid oxidation, and mitochondrial biogenesis.
Discovered in 2015, MOTS-c has gained attention for its potential role in combating metabolic disorders such as obesity, type 2 diabetes, and age-related insulin resistance. Research has also suggested that MOTS-c may mimic some of the beneficial effects of exercise, enhancing endurance, improving mitochondrial efficiency, and reducing inflammation. Additionally, MOTS-c appears to have neuroprotective properties, potentially aiding in cognitive function and protecting against neurodegenerative diseases. Due to its ability to influence key longevity pathways, it is being investigated as an anti-ageing intervention with the potential to extend healthspan.
Protocols
1. Metabolic Health & Insulin Sensitivity (Diabetes & Obesity Support)
Dosage: 5–10 mg per injection, 2–3 times per week
Cycle: 4–6 weeks, followed by a 2–4 week break
Administration: Subcutaneous (SC) injection, preferably in the morning or before exercise
Stacking: Works well with Tesamorelin or BPC-157 for metabolic support
Expected Benefits: Improved glucose regulation, increased insulin sensitivity, reduced fat accumulation
2. Fat Loss & Body Recomposition
Dosage: 10 mg per injection, 3 times per week
Cycle: 4–6 weeks, repeated as needed
Administration: SC injection, preferably pre-exercise
Stacking: Often combined with CJC-1295 and Ipamorelin for enhanced fat-burning effects
Expected Benefits: Increased fat oxidation, improved mitochondrial efficiency, better muscle definition
3. Endurance & Athletic Performance
Dosage: 10 mg per injection, 3 times per week
Cycle: 6–8 weeks, with 4-week breaks
Administration: SC injection, ideally before workouts or training sessions
Stacking: Often paired with AOD-9604 or GW-501516 for endurance enhancement
Expected Benefits: Enhanced stamina, reduced muscle fatigue, improved recovery rates
4. Longevity & Anti-Ageing
Dosage: 5 mg per injection, 2–3 times per week
Cycle: Long-term use with intermittent breaks (e.g., 4 weeks on, 4 weeks off)
Administration: SC injection, preferably in the evening
Stacking: Pairs well with Epitalon and NAD+ precursors for cellular rejuvenation
Expected Benefits: Improved mitochondrial function, reduced oxidative stress, enhanced lifespan potential
5. Neuroprotection & Cognitive Function
Dosage: 5–10 mg per injection, 2–3 times per week
Cycle: 6–8 weeks, followed by reassessment
Administration: SC injection
Stacking: Works well with Semax or Dihexa for brain health support
Expected Benefits: Increased cognitive resilience, reduced neuroinflammation, improved memory and learning
Further reading
MOTS-c functions by mimicking the effects of exercise at a cellular level, primarily by activating AMPK. This leads to improved glucose metabolism, enhanced insulin sensitivity, and increased fat oxidation. Studies have shown that MOTS-c levels naturally decline with age, which may contribute to age-related metabolic dysfunctions. Supplementing with MOTS-c could help counteract these effects, supporting longevity and metabolic health.
One of its most exciting applications is in endurance and physical performance. By improving mitochondrial function and enhancing ATP production, MOTS-c has been found to boost stamina and reduce fatigue in animal models. Athletes and biohackers have taken an interest in MOTS-c due to its ability to improve energy efficiency without the drawbacks of stimulants.
Additionally, MOTS-c’s neuroprotective properties are gaining attention. It has been found to cross the blood-brain barrier and protect neurons from oxidative damage, making it a potential candidate for preventing neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease.
Despite its promising benefits, MOTS-c research is still in its early stages. Most studies have been conducted in animals, with limited human trials available. While it appears to be safe and well-tolerated, long-term effects and optimal dosing protocols remain areas of ongoing research.
References
- Lee, C., et al. (2015). "MOTS-c: A mitochondrial-derived peptide that regulates muscle and fat metabolism." Cell Metabolism, 21(3), 443–454.
Reynolds, J. C., et al. (2021). "Mitochondrial peptides and metabolic regulation." Trends in Endocrinology & Metabolism, 32(9), 693–705.
Kim, K. H., & Lee, M. S. (2021). "MOTS-c: A new player in metabolic regulation and ageing." Journal of Molecular Medicine, 99(8), 1061–1071.
Lu, H., et al. (2019). "MOTS-c improves metabolic homeostasis and reduces obesity in mice." Nature Communications, 10, 828.
Zarse, K., & Ristow, M. (2020). "Mitochondrial peptides: Small signals with big impact on metabolism and ageing." Nature Reviews Endocrinology, 16(8), 461–475.