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MOTS-c

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c)

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A mitochondria-derived peptide with exercise-mimetic, insulin-sensitizing, and metabolic regulatory properties.

MOTS-c is not approved by the FDA for human use. It is sold strictly for research purposes only and is not intended for human consumption, diagnosis, treatment, or prevention of any disease or condition. Purchase and use is entirely at your own risk.

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What it is

MOTS-c is a 16-amino acid peptide encoded by the mitochondrial genome, making it part of the growing family of mitochondria-derived peptides (MDPs). It was identified in 2015 by researchers at USC.

Unlike humanin, MOTS-c exerts many of its effects in metabolic tissue — particularly skeletal muscle — where it activates AMPK (a master metabolic regulator) and produces effects that resemble exercise in some metabolic pathways. Circulating MOTS-c levels decline with aging and are elevated by exercise.

What research shows

  • Activates AMPK — the same pathway targeted by metformin and activated by exercise
  • Improved insulin sensitivity in animal models and early human data
  • Anti-obesity effects in high-fat diet rodent models
  • Exercise-like metabolic effects — often described as an "exercise mimetic"
  • Age-dependent decline in humans — correlates with metabolic health markers

What remains unknown

  • Optimal dosing and administration protocol in humans
  • Long-term safety profile
  • Whether exogenous MOTS-c produces benefits in already-exercising individuals
  • Full mechanism of action at the cellular level

Administration basics

Common use cases

Metabolic health, longevity protocols, insulin sensitivity, obesity research.

Half-life

Not well characterized. Thought to be short.

Administration

Subcutaneous injection.

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Research Protocols & Common Usage

Doses used in research

  • Animal studies have used 0.5–5mg per injection
  • Community protocols commonly report 5–10mg injected 2–3 times per week

Administration routes studied

Subcutaneous injection

Typical protocol duration

Community protocols commonly report 4–8 week cycles.

Common stacking protocols

  • MOTS-c + Humanin — combined as complementary mitochondria-derived peptides
  • MOTS-c + NAD+ precursors — combined for comprehensive mitochondrial and metabolic support
  • MOTS-c + Berberine — both activate AMPK; used together in some metabolic health protocols

Contraindications & combinations to avoid

  • Insulin-dependent diabetes — MOTS-c has significant effects on insulin sensitivity; blood glucose should be monitored
  • Should not be combined with berberine or metformin without monitoring blood glucose — additive glucose-lowering effects

Dosing information reflects doses used in published research and commonly reported community protocols only. This is not a personal recommendation. These compounds are not FDA-approved for human use in the contexts described. Consult a qualified healthcare provider before starting any protocol.

Considering stacking?

See the stacking guide for common combinations with MOTS-c and what to avoid.

Stacking guide

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Community Reviews

Reviews reflect individual user experiences with research compounds and are not medical advice. Results vary. These compounds are not FDA approved for human use. Peptelligent does not verify reported experiences.

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