MOTS-C Protocol

Dosing & Research

Last Updated: September 4, 2026

Chemical Identity

Amino Acid Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
Molecular Formula: C101H152N28O22S2
Molecular Weight: 2174.6 g/mol
CAS Number: 1627580-64-6

Exercise mimetic research, Insulin sensitivity, Mitochondrial stress adaptation, Healthy aging studies

Evidence Level

Animal Models Primary

Species Studied

Human • Mouse • Rat

Half-Life

~4 Hours (estimated)

Administration

Subcutaneous

Frequency

3x weekly (weeks 1-4 initial); 1x weekly (weeks 5-8 maintenance)

How It Works

Exercise mimetic research
Insulin sensitivity
Mitochondrial stress adaptation
Healthy aging studies

Dosing Structure

Dose

1 mg 3-5x weekly

Frequency

3x weekly (weeks 1-4 initial); 1x weekly (weeks 5-8 maintenance)

Notes

Initial Stage (Weeks 1-4): 5mg taken 3 times per week. Maintenance Stage (Weeks 5-8): 5mg taken 1 time per week. Cycle: 8 weeks with 4-week break. For more aggressive protocols, consider increasing doses to 10mg. Do not stack with AICAR. Inject: Abdomen, thigh, upper arm (rotate). Morning before exercise. Break: 2-4 weeks between continuous cycles.

Example Protocols

Dose: 1 mg 3-5x weekly

Frequency: 3x weekly (weeks 1-4 initial); 1x weekly (weeks 5-8 maintenance)

Duration: 6-8 weeks

Off Period: Not listed

Calculate dosing →

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Protocol Notes

•

Initial Stage (Weeks 1-4): 5mg taken 3 times per week.

•

Maintenance Stage (Weeks 5-8): 5mg taken 1 time per week.

•

Cycle: 8 weeks with 4-week break.

•

For more aggressive protocols, consider increasing doses to 10mg.

•

Do not stack with AICAR.

•

Inject: Abdomen, thigh, upper arm (rotate).

•

Morning before exercise.

•

Break: 2-4 weeks between continuous cycles.

What Is MOTS-C?

MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial genome - making it one of the few known mitochondria-derived peptides (MDPs). It functions as a mitokine: a hormone-like signal secreted by mitochondria in response to metabolic stress that communicates with the nucleus and systemic tissues. Research focuses on its role in insulin sensitivity, metabolic regulation, exercise mimicry, and longevity.

Research Observations - Not Medical Claims

▸Insulin sensitivity: MOTS-c administration in mice on a high-fat diet significantly improved insulin sensitivity and reduced fat accumulation - effects were comparable to metformin in the same model (PMID: 25735772).
▸Exercise mimicry: MOTS-c increases with aerobic exercise in humans. Exogenous MOTS-c injection in aged mice improved exercise capacity and muscle function - proposed as a potential exercise-mimetic compound (PMID: 31004536).
▸Longevity association: MOTS-c levels decline with aging. Genetic variants in the MOTS-c locus are associated with longevity in Japanese centenarian populations (PMID: 25735772).
▸Nuclear translocation: Under metabolic stress, MOTS-c translocates to the nucleus and regulates gene expression - a unique mechanism among peptide hormones (PMID: 31485084).
▸Metabolic inflammation: MOTS-c reduces inflammatory cytokines (TNF-α, IL-6) in adipose tissue and liver in metabolic disease models.