MOTS-C is a mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA region. Research has positioned it as a signaling molecule connecting mitochondrial status with nuclear and metabolic responses. Experimental studies have examined AMPK activation, glucose handling, fatty-acid metabolism, exercise-related signaling, insulin sensitivity, and age-associated physical decline. Much of the intervention evidence comes from animal models, while human studies have also evaluated endogenous MOTS-C biology and exercise responses.