Mitochondrial-derived peptide encoded by the mitochondrial genome. Studied for roles in metabolic regulation, exercise performance, and longevity signaling.
MOTS-c is a peptide encoded by the mitochondrial genome rather than the nuclear genome, making it unusual among known signaling peptides. It was discovered in 2015 and functions as a mitochondrial-derived signaling molecule. Research has examined it for roles in metabolic regulation, exercise adaptation, and longevity, with animal studies showing notable effects and early human research underway.
Metabolic Regulation Research
MOTS-c appears to regulate metabolic flexibility — the ability to switch between burning glucose and fat for energy. Animal studies showed that MOTS-c administration to obese mice improved insulin sensitivity and reversed age-related metabolic decline.
Exercise and Physical Performance
Research in mice showed that MOTS-c administration increased exercise capacity and endurance, with effects on muscle metabolism. The peptide appears to act through AMPK activation — the same pathway activated by exercise itself — which has generated significant interest.
Aging and Longevity Research
Because MOTS-c is encoded by the mitochondrial genome and regulates metabolic programs, researchers have positioned it as a potential mediator of mitochondrial health and aging. Studies show MOTS-c levels change with age and metabolic stress.
Human Phase 1 Research
A first-in-human phase 1 trial published in 2021 showed that MOTS-c is safe and well-tolerated in older adults and produced changes in metabolic and inflammatory markers. This established human pharmacokinetics for the first time.
Improves insulin sensitivity and metabolic markers in animal models of obesity and aging.
Increases exercise endurance in mouse studies through AMPK pathway activation.
Encoded by the mitochondrial genome — a unique characteristic among known peptides.
Phase 1 human trial confirmed tolerability and showed metabolic marker changes.
Circulating MOTS-c levels associate with metabolic health in observational human studies.
Human research is at an early stage — phase 1 only as of most recent published data. Animal results, while promising, have not been confirmed in larger human efficacy trials. The appropriate dose, frequency, and route for human use are not established beyond the phase 1 safety findings. It is not FDA-approved.
Mitochondria are the power generators inside your cells, and they have their own separate DNA — a remnant of their ancient bacterial origins. Scientists recently discovered that the mitochondrial genome encodes small signaling peptides, and MOTS-c is one of them. MOTS-c is released from mitochondria when the cell is under metabolic stress — essentially acting as a distress signal that activates cellular programs to improve energy efficiency. It activates AMPK, an enzyme that senses cellular energy status and turns on fat burning and glucose uptake when energy is low. This is the same molecular pathway activated by exercise and calorie restriction, which is why researchers are interested in whether MOTS-c could mimic some of the metabolic benefits of physical activity.
Phase 1 human trial found MOTS-c well-tolerated at tested doses with no significant adverse events. Long-term safety in humans is not established — phase 1 trials are designed for safety and pharmacokinetics only. It is not FDA-approved. Research-grade purity and sterility are essential considerations for any research use given its early-stage status.
Emerging
This compound is in early-stage research. Evidence is limited to small studies or in vitro data.
Published Research Ranges
Primarily preclinical; 0.1–5mg/kg in animal studies; human trials underway
Research Context Only: These are ranges reported in published scientific studies for educational reference. They are not dosing recommendations. This is not medical advice. Always consult a qualified healthcare professional.
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A Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance
Research Education Only: This profile is for educational purposes only. All information is sourced from published scientific literature. This is not medical advice. Not for human consumption. Consult qualified medical professionals for any health decisions.
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