MOTS-c

The Mitochondrial Peptide for Metabolic Mastery and Longevity

What is MOTS-c?

MOTS-c (Mitochondrial ORF of the 12S rRNA Type-c) is a mitochondria-encoded peptide composed of 16 amino acids. Unlike most proteins in the body, which are encoded by nuclear DNA, MOTS-c is encoded within mitochondrial DNA (mtDNA)—making it a rare and powerful signaler of mitochondrial health, energy regulation, and cellular resilience.

Discovered in 2015 by researchers at the University of Southern California and the National Institutes of Health, MOTS-c acts as a metabolic regulator and cytoprotective agent, influencing pathways related to glucose metabolism, fat oxidation, insulin sensitivity, and cellular stress response. It is often referred to as a “mitokine”—a hormone-like peptide secreted by mitochondria that communicates with the rest of the body.

Key Mechanism: MOTS-c translocates to the nucleus under metabolic stress and regulates the expression of adaptive genes, particularly those related to AMPK activation, fatty acid oxidation, and insulin sensitivity.

Core Benefits of MOTS-c

🔥 Enhanced Metabolic Flexibility

  • Improves glucose utilization and insulin sensitivity
  • Promotes fat oxidation, making it ideal for weight loss and body recomposition
  • Increases mitochondrial efficiency and energy expenditure

🧬 Longevity and Anti-Aging

  • Activates AMPK—a key regulator of cellular energy and autophagy
  • Improves lifespan and healthspan in animal models
  • Mimics effects of caloric restriction without dietary restriction

💪 Exercise Performance & Recovery

  • Increases muscle glucose uptake and ATP production
  • Enhances endurance capacity and muscle regeneration post-exercise

🧠 Cellular Resilience and Stress Protection

  • Protects cells against oxidative stress and inflammation
  • Promotes cellular survival under metabolic or oxidative strain

Reference: Lee C, et al. “MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism.” Free Radic Biol Med. 2015; 86: 354–367. doi:10.1016/j.freeradbiomed.2015.05.003

Use Cases for MOTS-c

  • Weight loss and body fat reduction, especially visceral fat
  • Metabolic dysfunction, insulin resistance, or pre-diabetes
  • Anti-aging and longevity protocols
  • Exercise recovery, endurance enhancement, or mitochondrial support
  • Chronic fatigue, brain fog, or mitochondrial disorders

Mechanism of Action

MOTS-c works by activating critical cellular energy sensors and survival pathways, especially during periods of metabolic stress. Key pathways include:

  • AMP-activated protein kinase (AMPK) – Boosts energy production, mitochondrial biogenesis, and fat burning
  • PGC-1α – Enhances mitochondrial formation and function
  • FOXO and NRF2 – Increases antioxidant response and cellular detoxification
  • Insulin signaling pathways – Improves insulin receptor sensitivity and glucose uptake

These effects make MOTS-c a metabolic switch peptide—reprogramming cells to become more energy-efficient and stress-resistant.

Dosing and Administration (Research Use)

MOTS-c is typically administered via subcutaneous injection, with protocols ranging from short bursts to long-term cycling.

Typical Dosing Protocols:

  • Dose: 5–15 mg per injection
  • Frequency: 2–5x per week (e.g., Monday–Friday or 3-day split)
  • Timing: Morning, pre-exercise, or fasting states may enhance efficacy
  • Cycle: 4–8 weeks per cycle; repeat 2–3x per year for longevity purposes

Often stacked with SS-31, NAD+, or GHK-Cu in mitochondrial rejuvenation or anti-aging protocols.

Safety and Side Effects

MOTS-c has demonstrated an excellent safety profile in animal models and early human trials. As it is endogenously produced by the body, it is generally well-tolerated and non-toxic.

Reported Effects:

  • Improved endurance and energy levels
  • Mild appetite suppression
  • Improved sleep quality
  • No reports of hormonal suppression or metabolic rebound

Rare or mild side effects:

  • Temporary flushing or warmth
  • Mild fatigue or nausea (typically resolves quickly)
  • Injection site sensitivity

Reference: Kim KH, et al. “MOTS-c prevents muscle atrophy and regulates systemic energy homeostasis.” J Cachexia Sarcopenia Muscle. 2018;9(3):486–501.

Conclusion

MOTS-c is a next-generation peptide rooted in mitochondrial intelligence—bridging the gap between longevity science, metabolic optimization, and cellular performance. Whether you’re targeting fat loss, endurance, or lifespan extension, MOTS-c offers a biologically elegant solution that taps into the cell’s deepest regulatory systems.

As research continues to grow, MOTS-c is becoming a core component in cutting-edge biohacking, anti-aging, and mitochondrial enhancement protocols.