MOTS-c

Also: mitochondrial open reading frame of the 12S rRNA type-c

Longevity & cellular Metabolic & weight

Legal status United KingdomNot approved United StatesNot approved AustraliaNot approved

Research on peptidefix

7 papers: 1 human study, 3 animal studies, 2 cell studies, 1 review or preprint.

Listed suppliers United Kingdom15 United States11 Australia9 Europe10

Checked 2026-11-03

Legal status as understood on this date. Listed, not endorsed. How we list.

Summary

MOTS-c is a 16-amino-acid peptide encoded not in the cell nucleus but inside the mitochondrial genome, in the 12S rRNA region. It was identified in 2015. It occurs naturally in tissue and in blood, and the reviewed literature reports that circulating levels fall with age. The synthetic version sold by suppliers is a copy of that natural peptide.

What it targets

The original 2015 work reported that MOTS-c acts mainly on skeletal muscle, inhibiting the folate cycle and the purine synthesis attached to it, which activates AMPK, an enzyme central to cellular energy balance. A later study found the peptide moves into the cell nucleus under metabolic stress and influences nuclear genes, including antioxidant-response genes, interacting with stress-responsive transcription factors such as NRF2. In mice, treatment prevented insulin resistance from age and from a high-fat diet, prevented diet-induced obesity, and improved physical performance at young, middle and old ages, including when started late in life. The human observation reported alongside that mouse work is that exercise raises the body's own MOTS-c in muscle and blood; no trial in which MOTS-c was given to people was found in the literature reviewed for this page.

insulin resistance and diet-induced obesity in micephysical capacity and healthspan in micenuclear gene expression under metabolic stress in cultured cells

Clinical Research

Associations of Serum MOTS-c with Exercise Capacity and Antioxidant Markers in Young Males: A Cross-Sectional Study

Zhang Z, Zhang X, Wang C, Zhang Y, Bo H (2026). Antioxidants. human small cross-sectional human study, n=30 healthy men aged 18 to 25 (10 elite athletes, 10 recreationally active, 10 sedentary); association, not a trial

The mitochondrial-derived peptide MOTS-c improves bioenergetics in aging-associated granulosa cells and oocytes

Tsui KH, Cheng SH, Lin LT, et al. (2026). Reproduction and Fertility. in-vitro Aged human granulosa cells and oocytes from aged mice, in the laboratory

MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide

Rice MC, Imun M, Jung SW, et al. (2026). eLife. animal Bacteria, human and mouse monocytes, mouse peritonitis model

The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance

Lee C, Zeng J, Drew BG, et al. (2015). Cell Metabolism. animal cell culture, then mice (age-related and high-fat-diet models of insulin resistance)

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Reynolds JC, Lai RW, Woodhead JST, et al. (2021). Nature Communications. animal young, middle-aged and old mice, plus measurement of MOTS-c in human skeletal muscle and blood after exercise

The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress

Kim KH, Son JM, Benayoun BA, Lee C (2018). Cell Metabolism. in-vitro cultured cells under glucose restriction and other metabolic stress

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

Zheng Y, Wei Z, Wang T (2023). Frontiers in Endocrinology. review n/a (narrative review)

All research on MOTS-c →

Suppliers stocking MOTS-c

45 of the 49 listed suppliers. Each row opens its full listing.

Regulatory status

UKNot an approved medicine.

USNot an approved medicine. A draft HHS enforcement-discretion policy, published in the Federal Register on 30 October 2026, says HHS does not intend to take enforcement action against a state-licensed pharmacy, a federal facility or a licensed physician that compounds MOTS-c acetate under section 503A, for subcutaneous or intramuscular injection, while the FDA writes the 503A bulks list, when the policy's conditions are met. The policy does not approve MOTS-c, does not add it to the 503A bulks list, and is not binding. It covers a product with MOTS-c as the only active ingredient.

AUNot an approved medicine. Not listed by name in the Poisons Standard (October 2026).

Status as understood at 2026-11-03. Verify with the regulator in your country.

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