MOTS-c and Longevity and Anti-Aging: What Has Been Studied

What the research covers

MOTS-c has not been tested as an anti-ageing treatment in humans. Its ageing data 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.

In that 2015 study, MOTS-c treatment prevented insulin resistance linked to age in rodents (mouse). In cells, its actions led to activation of AMPK, an enzyme. A 2021 study tested MOTS-c in young, middle-aged and old rodents (mouse). It improved physical performance at all three ages. Treatment was also started late in life, three times a week. It increased physical capacity and healthspan in these old rodents (mouse).

The same 2021 paper also looked at people. Exercise raised their own MOTS-c in muscle and blood. A separate 2021 study had 30 people. It found only a trend toward higher blood MOTS-c after endurance exercise.

A PubMed search on 27 September 2026 found five clinical trial records on MOTS-c. All five measured the body's own MOTS-c levels. None gave MOTS-c to people. So there are no human data on MOTS-c dose, benefit or safety for ageing.

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. 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.
3. 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.