MOTS-c

MOTS-c is a mitochondria-derived peptide translated from the 12S rRNA open reading frame of mitochondrial DNA — a novel class of bioactive signaling molecules. In response to metabolic stress, MOTS-c translocates from mitochondria to the nucleus where it regulates gene expression through AMPK activation and interaction with antioxidant response elements (ARE). Key effects include promotion of glucose uptake via AMPK, inhibition of the folate cycle, and regulation of reactive oxygen species.

Exercise mimetic: MOTS-c administration recapitulates molecular signatures of endurance exercise in skeletal muscle.

Aging research: MOTS-c levels decline significantly with age; aged mice treated with MOTS-c showed improved exercise capacity and grip strength.

Longevity association: Specific MOTS-c variants associated with longevity and reduced disease risk in centenarian genetic studies.

Obesity resistance: Mice on high-fat diet with MOTS-c supplementation showed significant resistance to diet-induced obesity.

AMPK pathway: Direct AMPK activation drives GLUT4 translocation and improved muscle glucose uptake independent of insulin.