MOTS-c: Mitochondrial-Derived Peptide
Sixteen-amino-acid peptide encoded within the 12S rRNA region of mitochondrial DNA. Pre-clinical evidence for metabolic and longevity effects.
🐀 Animal
- Full name
- MOTS-c (mitochondrial open reading frame of the 12S rRNA-c)
- Class
- Mitochondrial-derived peptide
- Half-life
- Not well characterised in humans
- Route
- Subcutaneous / IP in research
- Developer
- Lee & Cohen labs (USC, 2015)
- Regulatory status
- No approval; investigational
What it is
MOTS-c was described by Lee and colleagues in 2015 as a 16-residue peptide encoded within the mitochondrial 12S rRNA gene. It circulates in human plasma and its levels decline with age, prompting interest in its role as a metabolic regulator and longevity peptide.
How it works
MOTS-c activates AMPK in skeletal muscle and influences nuclear gene expression via retrograde mitochondrial-nuclear signalling. This reduces lipid accumulation, improves insulin sensitivity, and increases metabolic flexibility in rodent models.
Exercise-induced stress elevates circulating MOTS-c in humans; it is plausible that MOTS-c mediates some metabolic benefits of exercise.
What the research shows
Most evidence is pre-clinical; limited human observational data on circulating levels.
Lee C. et al. (2015) — discovery and metabolic effects
Lee C. et al., Cell Metab 2015;21:443–454. 🐀 Animal
Mice on high-fat diet received MOTS-c injections; insulin sensitivity and body composition improved.
The peptide was detected in human circulation, and its action was independent of classic GLP-1/leptin pathways.
Limitations: Rodent data; human dosing unknown.
Reynolds JC et al. (2021) — exercise and MOTS-c in humans
Reynolds J.C. et al., Nat Commun 2021;12:470. 👥 Human studies
Circulating MOTS-c levels rose after exercise in healthy adults and correlated with metabolic markers.
Results support a physiological role in exercise adaptation, not therapeutic use.
Limitations: Observational; no intervention with MOTS-c in humans.
Safety and limitations
No controlled human administration data. Pre-clinical studies in mice showed no overt toxicity at therapeutic doses.
Products sold as MOTS-c in the grey market have unknown purity and bioactivity; human therapeutic use is not evidence-based.