What is MOTS-c?
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a mitochondrial-derived peptide composed of 16 amino acids. It plays a vital role in regulating metabolic homeostasis, insulin sensitivity, and energy expenditure. Studies indicate its potential applications in obesity, type 2 diabetes, aging, and skeletal muscle function.
MOTS-c is a naturally occurring peptide encoded by mitochondrial DNA, not nuclear DNA. It is produced in response to metabolic stress and acts as a regulator of energy balance and insulin sensitivity. It has been shown to mimic the effects of exercise at the cellular level, particularly in metabolic tissues such as muscle and fat. Research also suggests that its levels decrease with age, making it a molecule of interest in age-related metabolic decline [1].
New Update: In July 2026, an FDA advisory committee narrowly voted to recommend MOTS-c for the 503A compounding list. It has not been added to that list or approved for human use, and further rulemaking would be required. MOTS-c is sold for research use only.
MOTS-c Research
Metabolic Regulation
MOTS-c has demonstrated the ability to improve insulin sensitivity and regulate glucose metabolism. In murine models, it promoted glucose uptake in skeletal muscle and suppressed fat accumulation despite high-fat feeding. These effects are attributed to AMPK pathway activation, a key regulator of energy metabolism [2].
Aging and Longevity
Levels of MOTS-c decline with age, but supplementation in animal studies has reversed age-related physical decline. In aged mice, treatment improved endurance, metabolic flexibility, and even extended lifespan. These results suggest it may serve as a longevity-promoting peptide [3].
Muscle Function
MOTS-c plays a role in supporting muscle health by promoting mitochondrial biogenesis and increasing muscle fiber regeneration. In studies on aging mice, it enhanced muscle strength and prevented sarcopenia-related decline when combined with exercise regimens [4].
Bone Health
Early studies suggest that MOTS-c may protect against bone density loss. In an ovariectomy-induced osteoporosis model, supplementation mitigated bone loss and supported osteoblast activity, indicating a potential for future research into osteoporosis [5].
Cardiovascular Function
MOTS-c is being explored for its influence on cardiovascular markers. Initial findings show potential for reducing vascular inflammation and enhancing endothelial function. While mechanisms remain under investigation, it may contribute to overall cardiovascular resilience [2].
For our free peptide calculator, CLICK HERE. Research-grade MOTS-c is available from WellnessPeptides.
Disclaimer
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
Referenced Citations
- Lee C, Zeng J, Drew BG, et al. “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” Cell Metabolism. 2015. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905433/
- Kim KH, Son JM, Benayoun BA, Lee C. “The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.” Cell Metabolism. 2018. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905433/
- Reynolds JC, Lai RWS, Woodhead JST, et al. “MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.” Nature Communications. 2021. Available at: https://www.nature.com/articles/s41467-020-20790-0
- Hao Y, Xu Y, Zhang H, et al. “MOTS-c increases muscle regeneration and mitochondrial biogenesis in aged mice.” Histochemistry and Cell Biology. 2024. Available at: https://link.springer.com/article/10.1007/s00418-024-02274-0
- Lu H, Zhang L, Li R, et al. “MOTS-c attenuates bone loss in ovariectomized mice by regulating osteoblast activity.” Journal of Orthopaedic Translation. 2023. Available at: https://www.sciencedirect.com/science/article/pii/S2214031X23000363
