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MONOGRAPH No. 009
EVIDENCE BASEPreclinical
CLASS
Mitochondrial peptide
MW
2174.5 g/mol
ORIGIN
Mitochondrial 12S rRNA
MECHANISM
AMPK activation
EU STATUS
Research only
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⏳ Anti-Aging & Longevity

MOTS-C — encoded in your mitochondria.

MOTS-C (Mitochondrial Open reading frame of the twelve S rRNA type-c) is a peptide encoded within mitochondrial DNA itself — discovered in 2015. It activates AMPK, improves insulin sensitivity, and supports mitochondrial function. It is one of the few peptides in this category with a natural endogenous origin.

Last reviewed:

Why mitochondrial origin matters

MOTS-C is unusual in that it is not synthesised by nuclear genes but encoded within mitochondrial DNA. It is secreted from mitochondria in response to metabolic stress and acts as a retrograde signal to the nucleus, regulating nuclear gene expression. Serum MOTS-C levels decline with age in humans, making it an interesting longevity research target.

EVIDENCE SUMMARY
STRONG
AMPK activation & insulin sensitivity — Consistent animal data. Improved insulin sensitivity and glucose metabolism in rodent models including type 2 diabetes models.
MODERATE
Age-related decline (human correlation) — Human studies show declining serum MOTS-C with age, correlation with metabolic health markers. Not causal.
LIMITED
Exercise mimetic effects — Animal data suggesting MOTS-C mimics some beneficial effects of exercise training. Human trial data pending.

Molecular information

Molecular formula
C101H152N28O22S2
Molecular weight
2174.5 g/mol

Pharmacokinetics

Half-life (t½)
≈ 1.5 h
Source: Literature estimate (~1–2 h exogenous plasma)

Potency retained over time

Each line is one storage condition: it starts at 100% and falls as potency is lost. Above the dashed 80% line the material is considered reliable — hover for exact values.

Freezer −20 °C
36+ mo
Stable · >95% potency
Fridge 4 °C
4-5 wks
In use · after recon
Room 20 °C
5-6 days
Avoid · increased loss
Warm 37 °C+
<1 day
Critical · rapid degradation

⚠ Computed from molecular properties (sequence length, cyclisation, residues prone to oxidation or deamidation, light sensitivity), per compound. Indicative only — not lab-measured per batch.

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Frequently asked questions

What is MOTS-c? ▾

MOTS-c is a mitochondrial-derived peptide encoded within mitochondrial DNA (12S rRNA) rather than by nuclear genes. It is secreted under metabolic stress and acts as a retrograde signal to the nucleus, activating AMPK.

Why does its mitochondrial origin matter? ▾

Unlike most peptides it is encoded in mitochondrial DNA and signals from the mitochondria to the nucleus to regulate gene expression. Serum levels decline with age, making it a longevity research target.

What does the research show? ▾

There is strong animal evidence for AMPK activation and improved insulin sensitivity, including type 2 diabetes models, moderate human correlation of declining serum MOTS-c with age, and limited animal data suggesting exercise-mimetic effects.

Is MOTS-c an exercise mimetic? ▾

Animal data suggest it mimics some beneficial effects of exercise training, but human trial data are pending, so this remains preliminary.

Does MOTS-c decline with age? ▾

Human studies show serum MOTS-c declining with age and correlating with metabolic health markers, though this is correlational and not established as causal.

Is MOTS-c legal in the EU? ▾

It is sold as a research compound for laboratory use only.

References

  1. The paper that identified MOTS-c: a 16-amino-acid peptide encoded inside the mitochondrial 12S rRNA gene, acting through the folate cycle and AMPK. The metabolic findings — improved insulin sensitivity, less weight gain on a high-fat diet — are in mice, not people. Lee C, et al. Cell Metab. 2015;21(3):443–454. PMC4350682
  2. Follow-up work in mice mapping which plasma metabolite pathways shift after MOTS-c injection. Useful for mechanism, but note what is still missing across this whole literature: no study of administered MOTS-c in humans has reported pharmacokinetics or outcomes. Kim SJ, et al. Physiol Rep. 2019;7(13):e14171. PMC6640593

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