MOTS-c and Muscle Gain: What Has Been Studied

What the research covers

MOTS-c has not been tested for muscle gain in humans. The muscle data on this page come from rodent (mouse) studies. MOTS-c is a peptide of 16 amino acids. It is coded in mitochondrial DNA and was first reported in 2015. That first study found its main target organ appeared to be skeletal muscle.

A 2021 study tested MOTS-c in young, middle-aged and old rodents (mouse). It improved physical performance at all three ages. In a 2024 study, rodents (mouse) were immobilised with casting tape for 8 days. Immobilisation cut muscle mass by about 15%. Rodents (mouse) given MOTS-c by injection at 15 mg/kg a day lost about 5%. MOTS-c also lowered fatty acid levels in the muscle.

In people, studies have measured the body's own MOTS-c rather than giving it. A 2021 study of 30 people compared endurance exercise, resistance exercise and rest. Blood MOTS-c showed only a trend to rise after endurance exercise. Resistance exercise did not raise these peptides. A PubMed search on 27 September 2026 found no trial that gave MOTS-c to people. The search was MOTS-c[tiab] AND clinicaltrial[filter], which returned 5 records, none giving MOTS-c.

Sources

1. von Walden F, Fernandez-Gonzalo R, Norrbom J, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985) (2021). PMID 34351816 doi:10.1152/japplphysiol.00706.2019 Human, 30 people: acute endurance vs resistance exercise vs control; MOTS-c showed a trend to rise after endurance exercise only.
2. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun (2021). PMID 33473109 doi:10.1038/s41467-020-20790-0 Rodent (mouse): MOTS-c raised physical performance at 2, 12 and 22 months; late-life 3x/week treatment. Human exercise raised the body's own MOTS-c.
3. Kumagai H, Kim SJ, Miller B, et al. Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration. Am J Physiol Endocrinol Metab (2024). PMID 38170165 doi:10.1152/ajpendo.00285.2023 Rodent (mouse): 15 mg/kg/day MOTS-c injection for 8 days limited cast-induced muscle loss to about 5% versus about 15%.
4. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab (2015). PMID 25738459 doi:10.1016/j.cmet.2015.02.009 Discovery paper. Rodent (mouse): MOTS-c treatment prevented age-dependent and high-fat-diet insulin resistance and diet-induced obesity; AMPK activation in cells.