In longevity practice, MOTS-c is positioned as a metabolic resilience peptide—used to support energy utilization, insulin sensitivity, and exercise capacity as patients age. Discovered as a mitochondria-encoded 16–amino-acid signal, MOTS-c is part of the broader strategy to preserve metabolic flexibility, a foundation for healthy aging and functional performance.
Mechanistically, MOTS-c targets skeletal muscle and the folate–AICAR–AMPK axis, improving glucose handling and cellular stress responses; it can translocate to the nucleus under stress and regulate gene networks tied to proteostasis and metabolism. Preclinical work shows enhanced metabolic homeostasis and insulin resistance reversal, and MOTS-c levels appear exercise-responsive while declining with age—reinforcing its “stress-adaptation” role.
Evidence signals are strongest in animal models: MOTS-c improves physical performance in young and old mice and has been studied for cardiometabolic protection and inflammation modulation. Human data remain early; there are no completed, large randomized trials defining long-term efficacy or optimal dosing. Clinicians should frame MOTS-c as an investigational adjunct—use objective metrics (glucose control, VO₂-linked performance, HRV/recovery) and pair with foundational lifestyle care.
Regulatory note: MOTS-c is not FDA-approved; the FDA has flagged insufficient human safety data for compounding, and anti-doping authorities note unknown safety with anecdotal side-effects reported by users. If used in research-oriented protocols, ensure informed consent, quality verification, and cold-chain integrity consistent with medical-grade handling.