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MOTS-c

Mitochondrial-Derived Peptide / Metabolic Regulator

Also known as: Mitochondrial-Derived Peptide MOTS-c

A 16-amino-acid peptide encoded in mitochondrial DNA that activates AMPK, improves insulin sensitivity, & shows dramatic lifespan extension in mouse models.

Typical Dose

5–10 mg, 3–5x per week

Route

Subcutaneous injection

Cycle

8–16 weeks

Half-life

Unknown in humans; hours (estimated)

Storage

Lyophilized: 2–8°C. Reconstituted: 2–8°C, use within 30 days.

Overview

MOTS-c is a peptide encoded by a small open reading frame within the 12S rRNA gene of mitochondrial DNA — one of only a handful of peptides encoded by the mitochondrial genome. It acts as a metabolic hormone, circulating from muscle mitochondria to the nucleus & other organs where it activates AMPK (AMP-activated protein kinase), the primary cellular energy sensor.

AMPK activation drives: increased glucose uptake in muscle, fatty acid oxidation, mitochondrial biogenesis, & inhibition of anabolic pathways. In mouse models, MOTS-c injection prevented diet-induced obesity, reversed insulin resistance, & significantly extended lifespan. Plasma MOTS-c levels decline with age in humans, suggesting it may contribute to age-related metabolic decline.

MOTS-c levels in humans peak with exercise & decline with aging. Exogenous MOTS-c administration mimics the metabolic effects of exercise on skeletal muscle mitochondria.

Quick Start Guide

1

Reconstitute with 1 mL BAC water per 5 mg vial.

2

Inject 5–10 mg subcutaneously 3–5x per week.

Research Indications

Insulin sensitivity / metabolic health

Most Effective

AMPK activation drives glucose uptake, fatty acid oxidation, & reversal of insulin resistance in animal models. Mimics exercise-induced metabolic signaling.

Anti-aging / longevity

Moderate

Lifespan extension in mouse models. Declines with human aging, suggesting supplementation may counter age-related metabolic decline. No human longevity data yet.

Exercise performance

Moderate

Promotes the molecular adaptations of aerobic exercise in skeletal muscle mitochondria. May be useful for those unable to exercise or seeking enhanced adaptation.

Research Protocols

Metabolic health & longevity

8–16 weeks

Dose

5–10 mg

Frequency

3–5x per week SubQ

Route

SubQ abdomen

Peptide Interactions

SS-31Synergistic

Complementary mitochondrial mechanisms: SS-31 protects cardiolipin; MOTS-c drives AMPK/metabolic remodeling. Strong theoretical synergy.

HumaninCompatible

Both are mitochondria-derived peptides; combined use in longevity protocols is common.

Side Effects & Safety

Common

  • Injection site redness
  • Hypoglycemia risk (AMPK activation increases glucose uptake; monitor in diabetics or during fasting)

Uncommon

  • Headache
  • Fatigue (AMPK pathway shifts away from anabolism)

When to Stop

  • Signs of allergic reaction
  • Diabetics: monitor blood glucose carefully

How to Reconstitute

1

Wipe stopper. Add 1 mL BAC water. Swirl gently. Refrigerate.

Dosing math: 1 mL BAC water per 5 mg = 5000 mcg/mL. For 5 mg: 1.0 mL. For 10 mg: use 2 vials or 0.5 mL BAC water per 5 mg vial = 10000 mcg/mL.

Quality Indicators

Good — use as normal

  • Clear, colorless solution

Acceptable

  • Very faint tint

Discard immediately

  • Cloudiness
  • Particulate

What to Expect

Week 1–2

AMPK activation begins immediately. Blood glucose improvements may be measurable.

Week 3–8

Metabolic adaptations accumulating. Body composition improvements (fat loss, improved insulin sensitivity) more apparent.

Community Insights

Self-reported. Reflects user experience, not clinical outcomes.

Research References

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline & muscle homeostasis

Nature Communications · 2021

Demonstrates exercise-induced MOTS-c secretion, age-related decline in MOTS-c levels, & reversal of age-related physical decline with exogenous MOTS-c treatment.

Verify what you have

Information on this page applies to pharmaceutical-grade peptides. Purity & identity of research-grade products vary. Certipep provides independent ESI-TOF-MS & HPLC analysis with a signed analytical report.

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