MOTS-c

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within mitochondrial DNA. First described by Lee and colleagues in 2015, it is one of several so-called mitochondrial-derived peptides (alongside humanin) thought to act as signaling molecules that help coordinate cellular metabolism and stress responses. Endogenous MOTS-c rises with exercise in human skeletal muscle and circulation, which has driven interest in it as a potential "exercise-mimetic" and metabolic-aging target. Most of the evidence base is preclinical. In rodents and cell models, exogenous MOTS-c has improved insulin sensitivity, reduced diet-induced obesity, and enhanced physical capacity in young, middle-aged and old animals. Human data so far is largely observational (measuring natural MOTS-c levels in response to exercise) rather than from controlled trials of injected MOTS-c. As of 2026, MOTS-c is being evaluated in early human clinical trials (e.g., a Phase 2a study in prediabetes/overweight adults), but it is not an approved drug anywhere and remains a research compound. Material sold to consumers is research-use-only and not validated for human consumption. Claims about fat loss, endurance and "anti-aging" benefits in people should be treated cautiously: they are extrapolated mainly from animal studies and community anecdote, not from completed human efficacy trials.