MOTS-c

DNot approvedmitochondrial ORF of the twelve S rRNA type-cmitochondrial-derived peptide
In one paragraphMOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA rather than the nucleus, discovered in 2015. In mice it improves insulin sensitivity and protects against diet-induced obesity, and human blood levels fall with age and correlate with fitness. No controlled human trial has tested giving it to anyone. It is not approved anywhere.
Schematic 3D structure of MOTS-c
16 residues · mitochondrial-encoded, largely unstructured · schematic
Overall gradeD No human evidence
Human trials0 controlled
Outcomes graded4
Last reviewed2 September 2026
EvidenceWhat it isHow it worksUnknownsRegulationQuestionsReferences

What the human research shows

Genuinely interesting biology at the frontier of a new class — mitochondria turn out to encode signalling peptides — and zero human intervention evidence. The observational human work measures MOTS-c that people already have; it says nothing about injecting more.

OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
Insulin sensitivity / metabolic healthDNo human evidenceNot measurable0 controlledMouse models of diet-induced obesity and insulin resistance. Human data is observational — levels correlate with fitness and fall with age — which cannot show what supplementation would do.
Exercise capacityDNo human evidenceNot measurable0 controlledRodent exercise models; human correlation studies only.
LongevityDNo human evidenceNot measurableNoneAssociation studies of a mitochondrial variant in a Japanese cohort; not an intervention.
Safety in humansadverseDNo human evidenceNot measurableNoneNo human dosing study of any kind.
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 2 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

What it is

For most of modern biology, mitochondrial DNA was thought to encode only a handful of proteins for energy production. MOTS-c, identified in 2015, is one of a small group of peptides encoded there that act as signals to the rest of the cell — and to other tissues. That is a genuinely novel finding, and it is why the compound gets attention.

The distance between that finding and "inject this" is the entire clinical development process, none of which has been done.

How it is thought to work

It appears to activate AMPK, a cellular energy sensor, and to shift metabolism toward glucose use — in mouse muscle. Human blood levels are lower in older and less fit people, which is an association, not a mechanism established in people.

What is still unknown

  • Whether administering it does anything in a human being.
  • Dose, route, half-life and safety in humans — none established.
  • Whether the age-related decline is a cause of anything or a consequence.

Regulatory status

European Union
Unapproved medicinal product

No authorisation; sale for human use is an offence for the seller.

United States
Not approved

Sold as a research chemical.

Australia
Prescription-only or unapproved

Scheduled by the TGA; not available without a prescription.

Questions people actually ask

Does MOTS-c improve metabolism in humans?
Unknown. The metabolic effects are from mouse studies. Human research so far measures naturally occurring MOTS-c levels; it has never been given to people in a controlled trial.
Why do people say it is linked to longevity?
A mitochondrial variant affecting MOTS-c has been associated with longevity in a Japanese cohort. That is an association in people who inherited it, not a result of taking anything.

References

  1. 1

Change log

  • 2026-09-02Initial publication. All outcomes graded D on absence of human intervention trials.