MOTS-c
Metabolic Health, Anti-Aging
In short
- A 16-amino-acid peptide encoded in mitochondrial DNA rather than nuclear DNA — one of a small class of mitochondrial-derived peptides.
- The underlying biology is genuine and published in mainstream journals; the human therapeutic evidence is not there yet.
- Preclinical work centres on AMPK activation, insulin sensitivity, and exercise capacity.
- A naturally occurring polymorphism in the MOTS-c sequence has been associated with longevity in Japanese cohorts.
- No approved use, and no published human trial of administered MOTS-c.
Structure
How it works
MOTS-c is encoded within the mitochondrial 12S rRNA gene. It translocates to the nucleus under metabolic stress and regulates nuclear gene expression — a genuinely unusual mitochondrial-to-nuclear signalling mechanism.
The main described pathway is activation of AMPK, the cellular energy sensor, with downstream effects on glucose uptake, fatty acid oxidation, and the folate-methionine cycle. Effects reported in muscle include improved insulin sensitivity and exercise capacity.
What the research shows
In mice, MOTS-c administration improved insulin sensitivity, prevented diet-induced obesity, and improved physical performance in aged animals — findings published in Cell Metabolism and Nature Communications.
In humans, endogenous MOTS-c levels rise with exercise, and a sequence polymorphism has been associated with longevity in Japanese populations. These are observational findings about the endogenous peptide.
There is no published clinical trial of administering MOTS-c to humans.
Dosing in the literature
Figures below are quoted from published studies, with the species or population they were measured in. They are records of what was studied, not recommendations.
| Studied in | Amount | Route | Source |
|---|---|---|---|
| Mouse — metabolic and exercise capacity studies | Approximately 0.5–15 mg/kg/day depending on model | intraperitoneal | PubMed |
| Human — endogenous plasma levels and exercise response (observational) | Not an administered dose; measurement only | — | PubMed |
Commonly reported ranges
These are amounts people report using. They are not from any study, have not been evaluated for safety, and are reproduced here only because they circulate widely and are better seen alongside the evidence than instead of it.
| Reported by | Amount | Route |
|---|---|---|
| Commonly reported, often in short courses | 5–10 mg, two to three times weekly | subcutaneous |
No published human pharmacokinetic study establishes a dose, interval, or duration for this compound. Community figures below have no trial behind them and are reports of practice, not evidence. Rodent doses are per kilogram of mouse and do not translate by body-weight ratio. The human data concerns naturally occurring MOTS-c, not injected MOTS-c, and those are different questions.
Handling and storage
Supplied as a lyophilised powder requiring reconstitution with bacteriostatic water. The powder is comparatively stable; once reconstituted it is refrigerated and used within weeks. Track the date you reconstitute each vial — the Inventory section does this, and it is the difference between knowing a vial is three weeks old and guessing.
Subcutaneous injection. Intermittent rather than daily dosing is the commonly described pattern, generally reasoned from the exercise-mimetic framing rather than from any study.
Side effects
No human safety data for administered MOTS-c exists. Rodent studies did not report significant toxicity at the doses used.
Community reports mention injection-site reactions and occasional fatigue or flushing.
Because the mechanism is AMPK activation and metabolic modulation, interaction with glucose-lowering medication is the theoretically relevant concern, and it is uncharacterised.
Combinations
No interaction data. Combining with other metabolic agents — GLP-1 agonists, metformin, other AMPK activators — targets overlapping pathways and is unstudied in combination.
Research status
The foundational work is from Pinchas Cohen's group at USC, published in Cell Metabolism (2015) and subsequently. The mitochondrial-derived peptide field is legitimate and active.
What does not exist is a registered clinical trial of MOTS-c as a therapeutic. The gap between "interesting endogenous signalling peptide" and "useful injectable" has not been crossed.
Legal status
Not approved in any jurisdiction. Sold for research use only.
WADA status
Not specifically named on the Prohibited List. Falls under WADA class S0, which prohibits any pharmacological substance not currently approved by any governmental regulatory health authority for human therapeutic use. Treat it as prohibited in sport.
Conclusion
MOTS-c rests on better science than most of this library — the mitochondrial-derived peptide field is real, published in strong journals, and independently studied.
What has not happened is any human trial of giving it to people. The biology being sound is not the same as the injection being useful, and that distinction is where nearly all the marketing lives.
Sources
Track your own MOTS-c protocol
Peppers logs your doses, models your levels from this half-life, tracks your vials and tells you when you will run out. Free on iPhone.
Reference and educational information only. Not medical advice. Nothing here diagnoses, treats, or prescribes, and nothing here is a recommendation to use any compound. The compounds described are research chemicals and are not approved for human consumption. Legal and anti-doping status change — the review date above is when these claims were last checked. Talk to a qualified clinician about anything you intend to take.