MOTS-c
A mitochondrial-derived peptide linked to cellular energy regulation. Encoded in mitochondrial DNA.
Mechanism of Action
Mitochondrial support compound promoting cellular energy and longevity markers.
Evidence Chain
MOTS-c
COMPOUND
1 Research Goal
• Anti-Aging & Longevity
Evidence Strength
9 articles sourced
Knowledge Graph
(10 connections)Research Evidence
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Overview
MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA-c) is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 12S rRNA gene — a remarkable discovery that challenged the long-held belief that mitochondrial DNA only encoded protein components of the oxidative phosphorylation system. Discovered by researchers at the University of Southern California, MOTS-c has become a significant focus in longevity and metabolic research.
Mechanism of Action
MOTS-c primarily acts by modulating cellular energy metabolism. It translocates to the nucleus under metabolic stress, where it regulates the expression of nuclear genes involved in antioxidant response and mitochondrial function. MOTS-c activates AMPK (AMP-activated protein kinase), the cellular energy sensor, promoting glucose uptake and fatty acid oxidation while inhibiting the folate cycle and de novo purine biosynthesis. This metabolic reprogramming shifts cells toward oxidative metabolism and improves insulin sensitivity. MOTS-c also influences the mevalonate pathway, connecting it to cholesterol biosynthesis and protein prenylation.
Research Highlights
Animal studies have demonstrated that MOTS-c administration improves insulin sensitivity, reduces obesity, and enhances exercise capacity in aged mice. Research has shown that MOTS-c levels decline with age, and that restoring MOTS-c can reverse age-related metabolic decline. Studies have explored its potential in type 2 diabetes, obesity, and longevity interventions. MOTS-c has been shown to improve markers of metabolic health in high-fat diet models. Human studies have identified correlations between MOTS-c levels, exercise capacity, and metabolic health markers.
Dosage & Administration
In research, MOTS-c has been administered via subcutaneous injection at doses of 5-10 mg per week in animal models. No standardized human dosing protocols exist. For research use only (RUO).
Safety Profile
Preclinical studies have reported favorable safety profiles, with no significant adverse effects at therapeutic doses. Long-term safety data in humans is absent. As an investigational peptide, full safety characterization is pending. Not approved by the FDA for any indication.
References
Lee C, et al. MOTS-c: a mitochondrial-derived peptide. Cell Metab. 2015. Lee C, et al. MOTS-c and exercise. FASEB J. 2019. Lu H, et al. MOTS-c and metabolic regulation. Aging Cell. 2019. All content is for educational and research purposes only.
FDA 2026 Regulatory Update
As of April–June 2026, this compound was among the 14 peptides formally removed from the FDA's Category 2 restricted compounding list following review by the Pharmacy Compounding Advisory Committee (PCAC). This regulatory shift permits licensed compounding pharmacies to produce and dispense this compound under appropriate oversight, subject to final 503A Bulks List adjudication expected following the July 23–24, 2026 PCAC meeting. This does not constitute FDA approval for therapeutic use. All information on this page is for research purposes only.
Related Compounds
Synergy & Compatibility
(5)Computational assessment of bio-regulatory compatibility with compounds sharing research goals. Scores reflect half-life alignment, receptor target overlap, and bioavailability data.
Computational assessment based on available pharmacology data. Does not account for individual variability, dose-dependent effects, or unstudied interactions. For research use only.
Community Observations
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For research use only. Not medical advice.