MOTS-c

MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial genome — specifically within the 12S rRNA gene. It was discovered in 2015 by Dr. Changhan David Lee's laboratory at USC and represents a fascinating class of signaling molecules: mitochondrial-derived peptides (MDPs). MOTS-c functions as a metabolic regulator that can translocate to the cell nucleus during metabolic stress, where it directly regulates gene expression related to cellular metabolism.

It has been described as an "exercise mimetic" because it activates AMPK (the same pathway activated by exercise) and improves glucose uptake and utilization. Research has shown that MOTS-c levels decline with age, and supplementation in aged mice restores physical capacity and metabolic function to levels comparable to young animals. The peptide also reduces myostatin expression (a negative regulator of muscle growth), improves insulin sensitivity, and has been shown to prevent high-fat-diet-induced obesity in animal models. MOTS-c represents a new frontier in metabolic peptide therapy, bridging the gap between mitochondrial biology and whole-body metabolism.