VialOwlLibrary / Longevity
MOTS-c
Also known as Mitochondrial open reading frame of the 12S rRNA type-c
Animal studies only
A 16 amino acid peptide encoded by mitochondrial DNA that affects cellular energy metabolism. Studied in cells and animals for metabolic effects; human research is limited to measuring natural levels.
Not an approved medicine. MOTS-c is not an approved medicine for this use in Australia or the United States. This page summarises published research for information only. It is not a recommendation to use MOTS-c, and VialOwl does not sell or supply it.
Background
MOTS-c is a 16 amino acid peptide encoded in mitochondrial DNA rather than in the cell nucleus. It was discovered in 2015 by researchers in Pinchas Cohen's laboratory at the University of Southern California. A company, CohBar, later tested a modified version called CB4211 in early human trials.
How it is thought to work
In cells and mice, MOTS-c acts mainly on skeletal muscle, where it disrupts the folate cycle and activates AMPK, a cellular energy sensor. Under metabolic stress it moves to the nucleus and changes gene activity.
What is claimed, and the evidence
| Claim | Evidence | Notes |
|---|---|---|
| Improved insulin sensitivity and protection from diet induced obesity | Animal studies only | Shown in mice in the 2015 discovery study. |
| Liver and blood sugar markers in obese people with fatty liver (analogue CB4211) | Small human studies | Phase 1b study of 20 people over 4 weeks reported lower ALT, AST and glucose; results announced by the company and this is a modified analogue, not MOTS-c itself. |
| Exercise performance, longevity and fat loss | No published evidence | Marketed claims extrapolated from mouse studies; no human trials of MOTS-c. |
Side effects
| Effect | How often | Notes |
|---|---|---|
| Injection site reactions | Common | Over 10 per cent in the CB4211 analogue study, mostly mild to moderate and short lived. |
| Effects of MOTS-c itself in humans | Frequency unknown | FDA identified no human exposure data on MOTS-c products by any route. |
| Immune reactions to the product Serious | Frequency unknown | FDA flagged a significant immunogenicity risk and peptide impurity concerns for compounded MOTS-c. |
Warnings
- FDA has found no human exposure data for MOTS-c and does not know whether it would cause harm.
- Human evidence is limited to a company reported trial of a modified analogue and measurements of natural blood levels.
- Unapproved products are not assessed by the TGA for quality, safety or efficacy and may be contaminated, non-sterile, underdosed, overdosed or contain a different substance altogether.
Regulatory status
- Australia
- Not included on the ARTG (unapproved). Not specifically listed in the Poisons Standard (June 2026).
- United States
- Not FDA approved. Nomination withdrawn and removed from 503A Category 2 in April 2026. In July 2026 an FDA advisory committee voted 7 to 5 to recommend it for the 503A bulks list; FDA has not finalised this.
Sources
- PubMed: The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
- PubMed: MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation
- BioSpace: CohBar announces positive topline results from the phase 1a/1b study of CB4211
- FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (updated 22 April 2026)
- FDA: Pharmacy Compounding Advisory Committee meeting, 23 to 24 July 2026
Also in Longevity
From the VialOwl library, reviewed 26 September 2026. For education and general information. It is not medical advice and not a recommendation to use MOTS-c.