Important: MOTS-c evidence is currently limited to animal and cell studies. No human efficacy trials have been completed.
Overview
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded within the mitochondrial genome — one of the only peptides known to be encoded by mitochondrial DNA. It regulates metabolic homeostasis, insulin sensitivity, and exercise capacity by activating AMPK signaling. Circulating MOTS-c levels decline with age, and higher levels have been found in centenarians.
Mechanism of Action
MOTS-c activates AMP-activated protein kinase (AMPK) in skeletal muscle and liver, mimicking the metabolic effects of exercise and caloric restriction. It also regulates the folate cycle and one-carbon metabolism, affecting nucleotide synthesis, methylation reactions, and redox balance. Under metabolic stress, MOTS-c translocates to the nucleus where it regulates stress-response genes.
Research Evidence
- Discovered by Changhan David Lee at USC; published in Cell Metabolism (2015)
- Higher circulating MOTS-c levels found in centenarians vs. younger adults (Nature Communications, 2021)
- Activates AMPK to improve insulin sensitivity and increase fat oxidation
- Regulates folate cycle and one-carbon metabolism
- Translocates to the nucleus under metabolic stress to regulate gene expression
Bottom line: MOTS-c is a mitochondrial-derived peptide that activates AMPK to mimic the metabolic effects of exercise, with declining levels linked to aging and metabolic disease.
Research Protocols & Dosage
Evidence-based research protocols, administration routes, and dosage considerations for MOTS-c are detailed in the full compound profile. See also: Dosage guide for MOTS-c.
Sourcing & Quality
MOTS-c is available from Purgo Labs with third-party COA verification and research-grade purity standards. View MOTS-c at Purgo Labs.