Introduction:

MOTS-C is a mitochondrial-derived peptide (MDP) discovered in 2015 and studied for its role in metabolism, exercise performance, and aging.¹ While most evidence comes from animal and cell studies, human clinical trials are now emerging. This article reviews the current state of MOTS-C research.

Preclinical Research

• Initial studies showed MOTS-C activates AMPK, improves glucose uptake, and reduces obesity-related insulin resistance.¹
  
• In mouse models, MOTS-C extended lifespan and improved markers of physical and metabolic health.²
  
• These findings positioned MOTS-C as a candidate for metabolic and geroscience research.

Human Studies

• Exercise & Aging (2021): Reynolds et al. reported that MOTS-C rises during physical activity and declines with age. Supplementation in older adults improved exercise capacity in early-stage trials.³
  
• Metabolic Health (Ongoing): Small clinical studies are investigating MOTS-C’s effects on insulin sensitivity and glucose control. Results are promising but unpublished.
  
• Longevity Research: Exploratory trials are considering MOTS-C as part of broader anti-aging interventions, though no FDA-approved therapies exist.

Current Clinical Trial Status

• Phase I/II: Safety and metabolic endpoints are being tested in small cohorts.
  
• Not FDA-approved: MOTS-C remains a research-use-only compound.
  
• Future Directions: Larger, randomized human trials are needed to confirm metabolic and aging-related effects.

Challenges & Unknowns

• Limited data: Only a handful of small human trials exist.
  
• Long-term effects: Unknown, especially regarding aging and cancer risk.
  
• Regulation: Without FDA approval, use is restricted to laboratory research.

Summary

MOTS-C has moved from preclinical promise to early human trials, with initial findings supporting roles in metabolism, exercise, and aging. However, most of the evidence remains preclinical, and large-scale trials are needed to confirm its safety and efficacy. MOTS-C is one of the most intriguing mitochondrial peptides, but its clinical future is still unfolding.

FAQs About MOTS-C Clinical Trials

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References

1. Lee C, et al. “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” Cell Metab. 2015;21(3):443–454. https://pubmed.ncbi.nlm.nih.gov/25738459/
   
2. Lu H, et al. “Mitochondrial-derived peptide MOTS-c increases healthspan and lifespan in mice.” Aging Cell. 2019;18(6):e13030. https://pubmed.ncbi.nlm.nih.gov/31608986/
   
3. Reynolds JC, et al. “MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline.” Nat Commun. 2021;12:470. https://pubmed.ncbi.nlm.nih.gov/33563973/