MOTS-c (10 mg vial)

Protocol Overview

Concise summary of the regimen.

Dosing & Reconstitution

Frequency: Inject once daily subcutaneously. Stay at each dose level for approximately 2 weeks before increasing, and monitor for any adverse reactions. For 10 unit (0.10 mL) or smaller administrations, consider 30- or 50-unit insulin syringes for improved readability.

Reconstitution Steps

1. Draw 3.0 mL bacteriostatic water with a sterile syringe.
2. Inject slowly down the vial wall; avoid foaming.
3. Gently swirl until dissolved (do not shake vigorously).
4. Label with reconstitution date and refrigerate at 2 to 8 °C, protected from light.
5. Use within 7 days for optimal potency. At 3.33 mg/mL, 1 unit = 0.01 mL » 33.3 mcg on a U-100 insulin syringe.

Storage Instructions

Proper storage preserves peptide quality.

• Lyophilized: store at -20 °C or below in dry, dark conditions; include desiccant if available.
• Reconstituted: refrigerate at 2 to 8 °C; peptide degrades rapidly at room temperature (~25% activity loss

after 24 hours at 4 °C). Use within 7 days for best potency.

• Aliquoting: prepare single-use aliquots and freeze at -20 °C if needed; avoid freeze-thaw cycles.
• Allow vials to reach room temperature before opening to reduce condensation uptake.

Supplies Needed

Plan based on an 8 to 12 week daily protocol with gradual titration.

Peptide Vials (MOTS-c, 10 mg each):

• 8 weeks: ~3 vials. 12 weeks: ~6 vials. 16 weeks: ~9 vials.

Insulin Syringes (U-100):

• Per week: 7 syringes (1/day).
• 8 weeks: 56. 12 weeks: 84. 16 weeks: 112.

Bacteriostatic Water (10 mL bottles):

• 8 weeks (3 vials): 1 bottle. 12 weeks (6 vials): 2 bottles. 16 weeks (9 vials): 3 bottles.

Alcohol Swabs:

• Per week: 14 swabs.
• 8 weeks: 112 (2 x 100-count). 16 weeks: 224 (3 x 100-count).

Important Notes

Practical considerations for consistency and safety.

• Use new sterile insulin syringes for each injection; dispose in a sharps container.
• Rotate injection sites (abdomen, thighs, upper arms) to reduce local irritation and prevent

lipohypertrophy.

• Inject slowly; wait a few seconds before withdrawing the needle.
• Document daily dose, injection site, and any observations to maintain consistency.
• Discontinue use and consult a medical professional if any concerning symptoms arise.

How This Works

MOTS-c functions as a metabolic stress signal that helps optimize energy usage during nutrient stress or exercise. Its primary mechanism is AMPK activation through inhibition of the folate cycle, causing accumulation of AICAR (an AMP analog). Activated AMPK shifts cells into an energy-efficient mode: enhancing glucose uptake, fatty-acid oxidation, and mitochondrial respiration while downregulating fat storage and gluconeogenesis. MOTS-c can also translocate to the cell nucleus under stress conditions and upregulate antioxidant and stress-response genes. This retrograde signaling from mitochondria to nucleus increases expression of cytoprotective enzymes, helping cells cope with oxidative stress. Research indicates MOTS-c may also modulate mTOR and inflammatory pathways, contributing to lifespan and healthspan effects. Its actions resemble those of exercise and metformin at a cellular level.

Benefits & Side Effects

Observations from preclinical literature (no human clinical trials completed to date).

• Metabolic Health: Improves insulin sensitivity and glucose metabolism in mouse models; prevents

diet-induced insulin resistance.

• Weight & Fat Reduction: Prevents obesity and reduces visceral fat in obese mice through increased

energy expenditure and fat oxidation.

• Post-Menopausal Metabolism: Mitigates metabolic decline in ovariectomized mice; prevents

menopause-related fat gain and insulin resistance.

• Physical Performance: Enhances exercise capacity and counters age-related frailty; old mice ran 2

times longer on treadmill tests.

• Organ Protection: Reduces liver fat accumulation, improves cardiac function, and may support cognitive

function in preliminary studies.

• Bone & Immunity: Promotes osteoblast activity, inhibits osteoclast formation; modulates immune aging.
• Safety: No adverse effects reported in preclinical studies; human tolerability unknown. A modified analog

(CB4211) showed good tolerability in a Phase 1 trial.

• Note: these benefits have been demonstrated only in controlled research settings (mice or cells).

Translation to humans requires clinical studies.

Lifestyle Factors

Complementary strategies for best outcomes.

• Pair with a balanced, protein-forward diet tailored to energy needs.
• Combine resistance training and aerobic activity to reinforce metabolic adaptations and AMPK signaling.
• Prioritize sleep (7 to 9 hours) and stress management to support mitochondrial health and recovery.
• Consider intermittent fasting or caloric restriction, which may synergize with MOTS-c's AMPK-mediated

effects.

Injection Technique

General subcutaneous guidance from clinical best-practice resources.

1. Clean the vial stopper and skin with alcohol; allow to dry.
2. Pinch a skinfold; insert the needle at 45 to 90 degrees into subcutaneous tissue.
3. Do not aspirate for subcutaneous injections; inject slowly and steadily.
4. Wait 5 to 10 seconds before withdrawing; dispose of syringe in sharps container.
5. Rotate sites systematically (abdomen, thighs, upper arms) to avoid lipohypertrophy.

References

Source citations for further reading.

1. Lee C, Zeng J, Drew BG et al. MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (Cell Metabolism, 2015).
2. Wan W et al. MOTS-c: effects and mechanisms related to stress, metabolism and aging (J Translational Medicine, 2023).
3. Reynolds JC et al. MOTS-c is an exercise-induced regulator of age-dependent physical decline (Nature Communications, 2021).
4. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging (Int J Mol Sci, 2022).