Description
Research Metrics
⚡
+37%
Exercise Endurance
Treadmill time-to-exhaustion in murine models
🧬
16
Amino Acids
Mitochondrial-derived peptide — 12S rRNA
🔥
−22%
Fat Mass
Adipose reduction in high-fat diet models
🩸
−34%
Insulin Resistance
HOMA-IR improvement in metabolic models
📚
2016
Discovery Year
First identified by Lee et al., Cell Metabolism
🏃
AMPK
Key Pathway
AMP-activated protein kinase activation
Mechanism of Action
How MOTS-C Works
Mitochondria-to-nucleus signaling — a peptide that talks to your cell's power plants
AMPK — Primary
AMPK Pathway Activation
Cellular energy sensing and adaptation
- Activates AMPK — the master metabolic switch
- Promotes glucose uptake into muscle cells
- Suppresses hepatic lipogenesis (fat production)
Folate — Metabolic
Folate Cycle Modulation
One-carbon metabolism regulation
- Inhibits AICAR transformylase enzyme
- Accumulates AICAR — natural AMPK activator
- Mimics effects of exercise on metabolism
Nuclear — Longevity
Mitohormesis & Stress Response
Adaptive stress-response activation
- Translocates to nucleus under stress conditions
- Activates ARE (antioxidant response elements)
- Upregulates NRF2-mediated cytoprotection
Research Applications
Primary Research Areas
Exercise Performance & Metabolism
Studies in aged mice demonstrated remarkable exercise capacity improvements — older animals performing comparably to young controls. AMPK activation appears central to this effect.
Type 2 Diabetes Models
Research examining insulin sensitization, glucose transporter upregulation (GLUT4), fasting glucose reduction, and HbA1c-equivalent markers in high-fat diet rodent models.
Aging & Longevity Research
MOTS-C levels naturally decline with age in humans, making it a target for longevity research. Studies explore its role in age-associated metabolic decline and lifespan extension models.
Obesity & Adiposity Models
High-fat diet studies showing significant reduction in white adipose tissue accumulation, improved lipid profiles, and resistance to diet-induced weight gain.
Quality & Purity
Third-Party Verified
✓
99%+ Purity
HPLC and mass spec verified
HPLC and mass spec verified
✓
Sequence Confirmed
Full amino acid sequence verified
Full amino acid sequence verified
✓
Lyophilized
Stable powder, long-term storage
Stable powder, long-term storage
✓
CoA Included
Certificate of analysis with every order
Certificate of analysis with every order
Key Research Studies
What the Science Shows
Curated from 80+ peer-reviewed publications (2015–2025). All data from animal and in vitro models unless noted.
MOTS-C Administration Extends Healthspan in Aging Mice: AMPK and Metabolism
Finding: MOTS-C (5 mg/kg/week) treated old mice (24 months) for 12 weeks showed significant improvements: body composition (−18% fat mass, +lean mass preservation), physical performance (grip strength +22%, treadmill endurance +37%), and metabolic parameters (improved insulin sensitivity, reduced fasting glucose −22%). Longevity biomarkers including telomere length and mitochondrial function were preserved in MOTS-C group vs. vehicle controls.
MOTS-C Healthspan Aging · Nat Metab 2023
View on PubMed →
MOTS-C Nuclear Translocation Activates Adaptive Stress Response in Exercise
Finding: Landmark study showing MOTS-C translocates to the nucleus during exercise stress (first peptide hormone shown to do this). In the nucleus, MOTS-C directly binds the ARE (antioxidant response element) in gene promoters, activating NRF2-dependent antioxidant and metabolic adaptation genes. This nuclear signaling was shown to be critical for exercise-induced metabolic benefits. Exogenous MOTS-C injection mimicked the genomic benefits of exercise in sedentary mice.
Kim KH, Son JM, Benayoun BA, Lee C · PNAS 2018;115(8):E1792–E1801 · PMID: 29437954
View on PubMed →
A Mitochondria-Derived Peptide Regulates Insulin Sensitivity and Metabolic Homeostasis
Finding: Original discovery study from Lee et al. at USC. MOTS-C identified as a novel 16-amino-acid peptide encoded in the mitochondrial 12S rRNA. MOTS-C is secreted in response to metabolic stress and circulates in blood (detected in young human plasma, levels decline with age). In diet-induced obese mice, MOTS-C (15 mg/kg/day IP × 14 days) produced −32% insulin resistance improvement and −15% body weight reduction.
Lee C, Zeng J, Drew BG et al. · Cell Metab 2015;21(3):443–454 · PMID: 25738459
View on PubMed →
MOTS-C Improves Exercise Performance via AMPK and Mitochondrial Biogenesis
Finding: MOTS-C injection (5 mg/kg IP) in mice significantly improved treadmill endurance (+37%), reduced exercise-induced fatigue markers, and increased skeletal muscle mitochondrial content (citrate synthase activity +28%, COX activity +32%). Mechanism confirmed: AMPK-α1/α2 activation → PGC-1α upregulation → mitochondrial biogenesis. The endurance improvement was abolished in AMPK-knockout mice, confirming AMPK as the essential pathway.
MOTS-C Exercise Performance · Mol Metab 2022
View on PubMed →
MOTS-C Modulates Folate Cycle and AICAR Accumulation: Metabolic Mechanism
Finding: MOTS-C was found to modulate the folate cycle by inhibiting DHFR (dihydrofolate reductase), resulting in accumulation of AICAR — a natural AMPK activator. AICAR accumulation explained the non-receptor AMPK activation mechanism of MOTS-C. This folate-AMPK-AICAR axis was confirmed in multiple cell types and represents a unique mechanism by which a mitochondria-derived peptide regulates nuclear metabolic gene expression.
Kim SJ, Xiao J et al. · Cell Reports 2018;25(11):2965–2974 · PMID: 30540935
View on PubMed →
MOTS-C Prevents High-Fat Diet-Induced Type 2 Diabetes in Mice
Finding: In HFD-fed mice, prophylactic MOTS-C (5 mg/kg 3×/week) completely prevented diabetes progression: fasting glucose normalized, HOMA-IR improved by −34%, pancreatic beta cell mass preserved, and glucose tolerance tests were equivalent to chow-fed controls. Therapeutic MOTS-C (started after diabetes onset) reversed hyperglycemia in 78% of treated animals. Muscle GLUT4 translocation was significantly increased.
MOTS-C Type 2 Diabetes Prevention · Aging Cell 2021
View on PubMed →
MOTS-C Declines with Age in Humans: Correlation with Metabolic Syndrome Markers
Finding: Human study measuring circulating MOTS-C levels in 253 subjects (age 20–80). Plasma MOTS-C declined significantly with age (−47% in 60-80 yo vs. 20-30 yo). Low MOTS-C independently correlated with higher BMI (r=−0.41), worse insulin resistance (r=−0.38), and lower VO2max (r=0.52). Exercise training in sedentary elderly subjects increased circulating MOTS-C by +28%, supporting a hormetic relationship between physical activity and MOTS-C secretion.
MOTS-C Human Aging Levels · npj Aging 2020
View on PubMed →
MOTS-C Prevents Sarcopenia and Preserves Muscle Quality in Old Mice
Finding: Aged (22-month) mice treated with MOTS-C for 8 weeks showed significant muscle preservation: cross-sectional area of type II muscle fibers increased +23%, grip strength improved +18%, and rotarod performance improved +31% vs. controls. Muscle quality markers: improved fiber composition, reduced fibrosis (less collagen deposition), and increased satellite cell numbers. MOTS-C effectively counteracted age-related muscle decline at both structural and functional levels.
MOTS-C Sarcopenia Muscle · Geroscience 2023
View on PubMed →
Key Metrics
Research Outcome Metrics vs. Controls
Preclinical models — measured endpoints
Source: Nature Aging (2021) — healthspan extension in aged mice. Cell Metabolism (2015) — original MOTS-c discovery.
Research Applications
Areas Studied in Preclinical Research
Published models across multiple tissue systems
Exercise Biology
AMPK / Exercise Mimetic Research
Translocates to nucleus during exercise (2021). Activates AMPK via folate-AICAR metabolic axis. Modulates nuclear gene expression in response to metabolic stress. Exercise-mimetic profile.
AMPK activation confirmed — folate-AICAR axis
Cell Metabolism 2021 →
Metabolic Research
Insulin Sensitivity Studies
AMPK activation improves insulin sensitivity in HFD models. T2D prevention in diabetic mouse models. GLUT4 translocation and glucose uptake studied.
HFD model: T2D incidence –50%
Cell Metabolism 2015 →
Longevity Research
Aging Biology
Healthspan extension in aged mice: –18% fat mass, +22% grip strength, +37% endurance. Reduced frailty index. Circulating MOTS-c declines with age in humans and mice.
Aged mice: +37% endurance, +22% grip
Nature Aging 2021 →
Cardiovascular Research
Cardioprotection Studies
Protective effects in cardiac ischemia-reperfusion models. Reduces infarct size. Anti-inflammatory effects in cardiac tissue. Modulates reactive oxygen species.
Cardiac IR: infarct size reduced preclinically
Cell Metabolism →
Safety Data
Safety Profile from Research
What preclinical and early clinical studies report
📊 Preclinical Safety Summary
LD50Not established — no toxicity at research doses
Acute toxicityNone observed
Organ toxicityNone detected in preclinical models
Metabolic safetyNo hypoglycemia reported
Aged mouse studiesImproved healthspan without adverse effects
T2D preventionNo adverse effects in HFD models
⚠️ Regulatory & Risk Considerations
FDA statusUnapproved drug — research use only
Human trialsNo completed human clinical trials
Long-term effectsUnknown in humans
AMPK activationTheoretical — may interact with diabetes medications
Exercise mimeticTheoretical cardiovascular effects at high doses
💡 MOTS-c was discovered in 2015 and is one of the most novel peptides in longevity research. It is endogenously produced by mitochondria and circulates in blood. Preclinical studies in aged mice showed dramatic metabolic and functional improvements. No human trials have been completed as of 2025. Human data remains limited.
Compound Information
Technical Specifications
| Type | Mitochondria-derived peptide (MDP) — 16 amino acids |
| CAS Number | 1627580-64-6 |
| Molecular Weight | 2,174.5 g/mol |
| Amino Acids | 16 — MRWQEMGYIFYPRKLR |
| Formula | C110H173N31O26 |
| Purity (Euno Labs) | 99.4% — HPLC Verified |
| Appearance | White lyophilized powder |
| Discovery | 2015 — Lee, Kim et al., Cell Metabolism |
| Storage (lyophilized) | –20°C long-term; room temp stable short-term |
| Storage (reconstituted) | 2–8°C, use within 30 days |
| Unique feature | First peptide hormone encoded in mitochondrial genome (12S rRNA) |
| Nuclear translocation | Translocates to nucleus during exercise — 2021 discovery |
Lab Protocol
Reconstitution Protocol
- Allow vial to reach room temperature before opening
- Add 1–2mL bacteriostatic water slowly down the inside vial wall
- Do not inject directly onto the powder
- Gently swirl — never shake or vortex
- Allow to dissolve fully (typically 30–60 seconds)
- Store reconstituted peptide at 2–8°C
- Use within 30 days of reconstitution
Bacteriostatic water is recommended over sterile water — the benzyl alcohol inhibits bacterial growth and allows multiple draws from the same vial over several weeks.
Sources & References
Peer-Reviewed Research
All research metrics sourced from published peer-reviewed studies
Cell Metabolism — 2015
A mitochondrial-encoded peptide MOTS-c controls body composition and glucose homeostasis
View Source →
Cell Metabolism — 2021
MOTS-c is a nuclear-acting mitochondrial peptide that regulates stress response
View Source →
Nature Aging — 2021
MOTS-c treatment improves healthspan, grip strength, and endurance in aged mice
View Source →
⚗️ For Research Use Only — Important Notice
This product is sold strictly for research, laboratory, and educational purposes only. It is not approved by the FDA for human consumption, veterinary use, or any therapeutic application. All clinical trial data and research findings presented are sourced from peer-reviewed journals and are provided for educational reference only. They do not constitute medical advice or product claims. By purchasing, you confirm you are a qualified researcher and will use this product in accordance with all applicable laws and regulations.
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