A mitochondria-encoded peptide that regulates metabolic homeostasis and has demonstrated remarkable longevity effects.
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome — specifically within the 12S rRNA gene. Discovered in 2015, it is the first mitochondria-derived peptide (MDP) shown to translocate to the nucleus and directly regulate nuclear gene expression, establishing a new class of mitochondria-to-nucleus communication. MOTS-c is considered a “mitokine” — a hormone-like signal released from mitochondria in response to metabolic stress. Circulating MOTS-c levels decline with age and correlate with metabolic health, and MOTS-c polymorphisms in humans are associated with longevity in Japanese centenarian studies. It has demonstrated remarkable effects on insulin sensitivity, exercise performance, metabolic homeostasis, and lifespan in multiple model organisms.
* Benefits based on preclinical/animal research unless otherwise noted.
MOTS-c’s primary mechanism involves activation of AMPK (AMP-activated protein kinase) — the master cellular energy sensor — through inhibition of the folate cycle and de novo purine synthesis. When MOTS-c inhibits AICAR transformylase, AICAR accumulates and activates AMPK. AMPK activation then drives metabolic adaptations: increased fatty acid oxidation, enhanced glucose uptake via GLUT4 translocation, improved mitochondrial biogenesis via PGC-1α, and inhibition of mTOR. Under metabolic stress, MOTS-c translocates to the nucleus where it binds to the ARE (antioxidant response element) and activates Nrf2 target genes, providing cytoprotection. MOTS-c also modulates the gut microbiome and has direct anti-inflammatory effects through NF-κB inhibition.
Protocol Notes: Some practitioners use it pre-exercise for metabolic benefits. Start with lower doses. Limited human data — use with caution.
Add 2 mL bacteriostatic water to 10 mg vial → 5 mg/mL
When sourcing MOTS-c for research purposes, the following quality benchmarks should be verified before use.
Lyophilized: refrigerate. Reconstituted: refrigerate and use within 14 days.
The statements made within this website have not been evaluated by the US Food and Drug Administration. The products and information provided are not intended to diagnose, treat, cure, or prevent any disease. This website is intended for educational and research purposes only. Many peptides described on this site are not approved by the FDA for human therapeutic use and are classified as research chemicals. Nothing on this site constitutes medical advice.
Preliminary Evidence — Early-stage research only. Significant uncertainty about efficacy and safety in humans.
Peptides commonly used alongside MOTS-c for synergistic effects.
Tetrapeptide / Telomerase Activator
A tetrapeptide derived from the pineal gland that activates telomerase and has demonstrated lifespan extension in multiple animal models.
Learn More: EpithalonTelomerase Activator — Oral
Oral Epithalon for convenient telomerase activation and longevity support.
Learn More: Epithalon (Capsule)