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MOTS-c

Well Studied

Mitochondrial-Derived Peptide | Metabolic Regulator

Dose Start 5mg daily, increase to 10-15mg based on goals
Frequency Daily for metabolic support, or 3x weekly for anti-aging
Cycle 4-12 weeks depending on goals
Storage Refrigerate reconstituted solution at 2-8°C, use within 14 days

MOTS-c is a mitochondrial-derived peptide that operates as a mitohormone through the Folate-AICAR-AMPK pathway. Under metabolic stress, it translocates to the nucleus to bind stress-response transcription factors (NRF2, ATF1/ATF7), regulating genes involved in metabolism and cellular adaptation.

Mechanism of Action

Inhibits the folate cycle leading to AMPK activation. Under metabolic stress, translocates to nucleus to bind stress-response transcription factors, regulating genes involved in metabolism, insulin sensitivity, and cellular adaptation.

Key Benefits

  • Enhanced insulin sensitivity (~30% improvement)
  • Improved glucose metabolism and tolerance
  • AMPK pathway activation
  • Mitochondrial function optimization
  • Exercise performance enhancement (12-15% improvement)
  • Potential lifespan extension (6.4% median increase in mice)
Molecular Weight
2,174.6 Da
Chain Length
16 amino acids
Type
Mitochondrial-derived peptide (MDP)
Amino Acid Sequence
One-letter: MRWQEMGYIFYPRKLR
H₂N
M 1
O C
N
R 2
O C
N
W 3
O C
N
Q 4
O C
N
E 5
O C
N
M 6
O C
N
H
G 7
O C
N
Y 8
O C
N
I 9
O C
N
F 10
O C
N
Y 11
O C
N
P 12
O C
N
R 13
O C
N
K 14
O C
N
L 15
O C
N
R 16
COOH
Met
1

Methionine

Position 1

Arg
2

Arginine

Position 2

Trp
3

Tryptophan

Position 3

Gln
4

Glutamine

Position 4

Glu
5

Glutamic Acid

Position 5

Met
6

Methionine

Position 6

Gly
7

Glycine

Position 7

Tyr
8

Tyrosine

Position 8

Ile
9

Isoleucine

Position 9

Phe
10

Phenylalanine

Position 10

Tyr
11

Tyrosine

Position 11

Pro
12

Proline

Position 12

Arg
13

Arginine

Position 13

Lys
14

Lysine

Position 14

Leu
15

Leucine

Position 15

Arg
16

Arginine

Position 16

N-terminus C-terminus
Hydrophobic
Polar
Positive (+)
Negative (-)
Modified

Metabolic

  • Insulin Resistance

    Improves insulin sensitivity by ~30% in animal studies through AMPK activation.

  • Type 2 Diabetes Support

    Restores metabolic function via insulin receptor sensitization.

  • Obesity Prevention

    Promotes fatty acid oxidation despite identical caloric intake.

Anti-Aging

  • Age-Related Decline Reversal

    Reverses age-dependent physical decline in animal models.

  • Mitochondrial Biogenesis

    Enhances mitochondrial function via PGC-1α activation.

  • Lifespan Extension

    6.4% median lifespan extension observed in mice studies.

Exercise Performance

  • Running Performance

    12-15% improvement in running performance from single dose in studies.

  • Muscle Homeostasis

    Exercise induced 11.9-fold increase in skeletal muscle MOTS-c.

  • Recovery Support

    Supports muscle recovery and adaptation to exercise.

Subcutaneous injection is the primary route. Optimal administration is morning before exercise. AMPK activation occurs within 30 minutes.

GoalDoseFrequencyRoute
Metabolic health5-10mgOnce dailySubQ
Anti-aging protocol15mg3x weeklySubQ
Exercise performance10-15mgPre-workoutSubQ
Conservative start5mgOnce dailySubQ

Reconstitution Instructions

Materials Needed:
  • MOTS-c lyophilized powder
  • Bacteriostatic water
  • Insulin syringes
  • Alcohol swabs
  1. 1 Allow vial to reach room temperature (15-20 minutes)
  2. 2 Calculate required bacteriostatic water volume
  3. 3 Draw BAC water into insulin syringe
  4. 4 Inject slowly down vial side (not directly onto powder)
  5. 5 Gently swirl until dissolved (never shake vigorously)
  6. 6 Store at 2-8°C; use within 14 days
Metformin

Both activate AMPK; monitor for additive hypoglycemic effects.

monitor
NAD+ Precursors

Complementary mitochondrial enhancement through different pathways.

synergistic
Growth Hormone Peptides

Different mechanisms allow safe combination.

compatible
Berberine

Both are AMPK activators; monitor for additive effects.

monitor
Resveratrol

Complementary SIRT1/AMPK activation pathways.

synergistic
Diabetes Medications

May require dose adjustments to prevent hypoglycemia.

monitor
Week 1-2

AMPK pathway activation; initial glucose tolerance improvements

Week 2-4

Enhanced exercise capacity; improved insulin sensitivity

Week 4-8

Sustained metabolic benefits; potential body composition changes

Week 8-12

Maximum mitochondrial function enhancement; metabolic flexibility

Common Side Effects

  • Generally well-tolerated in animal studies with minimal side effects
  • Mild injection site reactions (redness, swelling)

Stop Signs - Discontinue if:

  • Severe allergic reactions or anaphylaxis
  • Recurrent hypoglycemia (<50 mg/dL)
  • Persistent severe injection site reactions
  • Unexplained weight loss >10% of baseline

Contraindications

  • Pregnancy or breastfeeding
  • WADA prohibited substance (banned for athletic competition)
  • Limited long-term human safety data

Good Signs

  • White to off-white powder with uniform appearance indicating proper storage
  • Clear, colorless solution without particles after reconstitution
  • Sequence verification (MRWQEMGYIFYPRKLR) with CoA >95% purity by RP-HPLC

Warning Signs

  • Limited human clinical data - start conservatively
  • WADA banned substance - not for competitive athletes

Bad Signs

  • Discolored powder or solution
  • Cloudy solution after reconstitution
  • No certificate of analysis available
  • Obesity and Insulin Sensitivity Study - Lee et al.
    Cell Metabolism (2015)

    Prevented obesity, improved insulin sensitivity by ~30% in high-fat diet mice.

  • Physical Performance Across Age Groups - Reynolds et al.
    Nature Communications (2021)

    Enhanced physical performance across age groups; exercise induced 11.9-fold increase in skeletal muscle MOTS-c.

  • Nuclear Translocation Study - Kim et al.
    Cell Metabolism (2018)

    Nuclear translocation within 30 minutes under metabolic stress.

  • Running Performance Study - Hyatt et al.
    Physiological Reports (2022)

    Single dose improved running time 12%, distance 15%.

  • Gestational Diabetes Study - Yin et al.
    Pharmacological Research (2022)

    Alleviated hyperglycemia in gestational diabetes model.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.