Mitochondrial-derived peptide

MOTS-c in Canada

Also known as Mitochondrial open reading frame of the 12S rRNA type-c · MOTS-c peptide · Mitochondrial-derived peptide MOTS-c · MOTSc

MOTS-c is a 16-amino-acid peptide encoded not in the nucleus but in the mitochondrial genome, inside the gene for the 12S ribosomal RNA. Identified in 2015 by Changhan Lee and Pinchas Cohen at the University of Southern California, it circulates in human blood, rises with exercise, declines with age, and in mice acts through AMPK to improve insulin sensitivity and physical capacity. The human data is a handful of small observational studies and one Phase 1 programme of an analogue. Canada Peptides carries research-grade MOTS-c as a 10 mg lyophilised vial, priced and shipped in CAD for laboratory and research use only.

Quick facts

Class: Mitochondrial-derived peptide (mtDNA-encoded); AMPK-pathway signalling peptide
Structure: 16 amino acids · Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg · ~2,175 Da
Half-life: Not established in humans; rodent plasma levels fall within hours after injection, with tissue effects lasting longer
Route in research: Intraperitoneal and subcutaneous in rodent studies; subcutaneous for the CB4211 analogue in Phase 1
Cadence in research: Once daily in most rodent protocols; every-other-day or intermittent in ageing studies
Storage: Lyophilised: refrigerated or frozen, dark. Reconstituted: refrigerated, used within weeks
Status in Canada

Pharmacology

MOTS-c signals through cellular energy metabolism rather than a classical cell-surface receptor. The 2015 Cell Metabolism paper showed that it inhibits the folate cycle and de novo purine biosynthesis, which causes the intermediate AICAR to accumulate; AICAR is a known activator of AMP-activated protein kinase, and AMPK activation is the downstream event most consistently reported. AMPK is the same node engaged by exercise, caloric restriction and metformin, which is why MOTS-c is often described as an exercise mimetic in molecular terms. AMPK in turn increases glucose uptake in skeletal muscle, promotes fatty-acid oxidation and mitochondrial biogenesis, and shifts cells toward energy conservation.

A second layer was described in 2018: under metabolic stress, MOTS-c translocates from mitochondria into the nucleus, where it associates with stress-responsive transcription factors including NRF2 and regulates nuclear gene expression. That makes it one of the few known molecules carrying signals from the mitochondrial genome to the nuclear genome directly. A 2021 Nature Communications paper from the same group showed that exercise raises MOTS-c in human muscle and plasma, and that treating aged mice with the peptide improved running capacity and metabolic markers.

Population genetics adds an unusual line of evidence. A single-nucleotide variant in the MOTS-c coding region, m.1382A>C, changes lysine 14 to glutamine and is common in East Asian populations; it has been associated with altered type 2 diabetes risk in Japanese cohorts, and the variant peptide behaves differently in cell assays.

Pharmacokinetically, MOTS-c is a small unmodified peptide and clears quickly. Rodent studies show plasma levels falling within hours after injection while metabolic effects persist for days, suggesting that the AMPK and nuclear signalling outlast the peptide itself. There is no published human pharmacokinetic study of administered MOTS-c, so half-life figures for the synthetic peptide in people are not derived from data.

MOTS-c FAQ

Is MOTS-c for sale in Canada?

Yes. Research-grade MOTS-c is available in Canada from Canada Peptides as a 10 mg lyophilised vial, priced and shipped in CAD. It is supplied strictly for laboratory and research use, not for human consumption.

What is MOTS-c?

MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial genome, within the 12S ribosomal RNA gene. It was identified in 2015 at the University of Southern California, circulates naturally in human blood, rises with exercise and declines with age, and in mice acts through AMPK to improve insulin sensitivity and physical capacity.

What does the research on MOTS-c actually show?

Consistent rodent data for improved glucose handling, reduced weight gain on a high-fat diet and better endurance in aged mice, with a defined AMPK mechanism. Human data consists of measuring the natural peptide in cohorts, not of giving the synthetic peptide to people. An analogue, CB4211, completed Phase 1.

What is the half-life of MOTS-c?

Not established in humans. In rodents, plasma levels fall within hours after injection while metabolic effects persist for days, which is attributed to downstream AMPK and nuclear signalling rather than circulating peptide. No human pharmacokinetic study has been published.

How was MOTS-c dosed in studies?

Mouse studies used 0.5 mg/kg daily for chronic metabolic experiments, 5 mg/kg for acute insulin-sensitivity tests, and 15 mg/kg daily or on alternating days in ageing studies, by intraperitoneal injection. There is no validated human dose, and this page does not recommend one; the material sold here is for research use only.

What side effects does MOTS-c research report?

Rodent studies report it as well tolerated with no toxicity at the doses used. There is no human safety data for MOTS-c itself, which is why the FDA declined to permit it in compounded medicines in 2023. Theoretical concerns include additive glucose-lowering with other agents; nothing has been demonstrated or excluded in humans.

Is MOTS-c legal in Canada?

MOTS-c is not a controlled substance in Canada, but it has no Health Canada approval for human use and no DIN. It may be sold for laboratory research, which is how it is sold here. It is generally considered prohibited for tested athletes as an AMPK activator under WADA's S4.4 category.

MOTS-c vs epithalon — what is the difference?

They are studied for different aspects of ageing: MOTS-c for mitochondrial and metabolic signalling through AMPK, epithalon for telomerase and circadian effects. MOTS-c has a defined mechanism and a strong rodent literature from a US laboratory; epithalon's evidence is older and largely from one Russian institute. Neither has controlled human outcome data.

MOTS-c in Canada

Quick facts

MOTS-c — for sale in Canada

What is MOTS-c?

Evidence at a glance

Pharmacology

Identity and chemistry

Storage and stability

Research indications

Research protocols

Interactions and stacking in research

Reconstitution and handling

Side effects and safety signals

Regulatory status in Canada

Further reading

MOTS-c FAQ

Research references