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Peptide

MOTS-c

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene. Discovered in 2015, it regulates metabolic homeostasis, insulin sensitivity, and has been shown to mimic some beneficial effects of exercise. MOTS-c levels naturally decline with age, and the peptide is being studied for age-related metabolic diseases.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
4
Outcomes
23
Graded outcomes
27122

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

4 conditions, plus general outcomes

Metabolic Health

Metabolic Health: outcomes studied for MOTS-c
GradeOutcomeEffectSizeStudiesPeopleStudies list
Insulin Sensitivity

MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance in mice. Human studies show plasma MOTS-c levels correlate positively with insulin sensitivity in lean individuals.

Improves (the measure goes up)Large effect11 studies

Studies that measured insulin sensitivity

and 1 more in the citations list

Glucose Metabolism

MOTS-c improves glucose metabolism in skeletal muscle by enhancing GLUT4 translocation via AMPK activation, reducing hyperglycemia and hyperinsulinemia in diet-induced obese mice.

Improves (the measure goes down)Large effect11 studies

Studies that measured glucose metabolism

and 1 more in the citations list

Aging & Longevity

Aging & Longevity: outcomes studied for MOTS-c
GradeOutcomeEffectSizeStudiesPeopleStudies list
Age-Related Insulin Resistance

Systemic MOTS-c injection restored peptide levels in aged mice and successfully reversed age-related skeletal muscle insulin resistance.

Improves (the measure goes down)Moderate effect11 studies

Studies that measured age-related insulin resistance

and 1 more in the citations list

MOTS-c Plasma Levels

Plasma MOTS-c levels decline with age in both mice and humans. Circulating levels are significantly lower in obese individuals and type 2 diabetes patients.

Improves (the measure goes down)Moderate effect3 studies

Studies that measured mots-c plasma levels

Body Composition

  • Muscle Homeostasis: improves
  • Body Weight: improves
  • Fat Accumulation: improves
Body Composition: outcomes studied for MOTS-c
GradeOutcomeEffectSizeStudiesPeopleStudies list
Muscle Homeostasis

MOTS-c acts as an exercise-induced mitochondrial-encoded regulator of muscle homeostasis, reducing myostatin and muscle atrophy signaling pathways.

Improves (the measure goes up)Moderate effect5 studies

Studies that measured muscle homeostasis

Body Weight

MOTS-c treatment reduced diet-induced obesity in mice by increasing energy expenditure and decreasing fat accumulation, particularly in liver tissue.

Improves (the measure goes down)Moderate effect4 studies

Studies that measured body weight

Fat Accumulation

MOTS-c significantly decreases hepatic fat accumulation and adipose tissue in high-fat diet fed animals, with improvements in liver lipid profiles.

Improves (the measure goes down)Moderate effect3 studies

Studies that measured fat accumulation

Physical Performance

MOTS-c significantly enhanced physical performance in young, middle-aged, and old mice. Late-life initiated intermittent treatment increased physical capacity and healthspan.

Improves (the measure goes up)Moderate effect3 studies

Studies that measured physical performance

Type 2 Diabetes

  • Pancreatic Islet Cell Senescence: improves
  • Type 2 Diabetes Risk: improves
Type 2 Diabetes: outcomes studied for MOTS-c
GradeOutcomeEffectSizeStudiesPeopleStudies list
Pancreatic Islet Cell Senescence

MOTS-c prevents pancreatic islet cell senescence and delays diabetes progression by acting as a senotherapeutic agent.

Improves (the measure goes down)Moderate effect4 studies

Studies that measured pancreatic islet cell senescence

Type 2 Diabetes Risk

In humans, serum MOTS-c levels are lower in patients with inadequately controlled T2DM (HbA1c >7%). Higher physical activity may rescue metabolic effects in individuals with certain mtDNA polymorphisms.

Improves (the measure goes down)Moderate effect5 studies

Studies that measured type 2 diabetes risk

General

  • Blood Glucose Control: improves
  • Pulmonary Function: improves
  • Oxidative Stress: improves
General: outcomes studied for MOTS-c
GradeOutcomeEffectSizeStudiesPeopleStudies list
Blood Glucose Control

9 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes down)Moderate effect10 studies

Studies that measured blood glucose control

Pulmonary Function

6 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect7 studies

Studies that measured pulmonary function

Oxidative Stress

5 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes down)Small effect6 studies

Studies that measured oxidative stress

Liver Protection

4 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect5 studies

Studies that measured liver protection

Anti-Aging

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies

Studies that measured anti-aging

Bone Mineral Density

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies
Anti-Inflammatory Activity

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies
Neuroprotection

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies
Cancer Cell Apoptosis

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies
Endothelial Function

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies
Pain

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes down)Small effect4 studies
Lipid Profile

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes down)Small effect3 studies
Sepsis Outcomes

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes down)Small effect3 studies

Key findings

  • Insulin SensitivityMetabolic HealthImproves (the measure goes up)
  • Glucose MetabolismMetabolic HealthImproves (the measure goes down)
  • Age-Related Insulin ResistanceAging & LongevityImproves (the measure goes down)

Studies cited

73 studies from PubMed

  1. Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetesFront Physiol, 2025 · PMID 40855115
  2. MOTS-C levels ın ındividuals with and without obesity and ıts association with ınflammation, insulin resistance and endothelial dysfunction.Archives of endocrinology and metabolism, 2025 · PMID 41004666
  3. MOTS-c in type 2 diabetes mellitus: From risk factors to cardiac complications and potential treatment.Life sciences, 2025 · PMID 41083123
  4. MOTS-c mimics remote ischemic preconditioning in protecting against lung ischemia-reperfusion injury by alleviating endothelial barrier dysfunction.Free radical biology & medicine, 2025 · PMID 39827923
  5. MOTS-c as a Potential Diagnostic-prognostic Biomarker for Myocardial Infarction.Cardiovascular & hematological agents in medicinal chemistry, 2025 · PMID 40353474
  6. MOTS-c relieves hepatocellular carcinoma resistance to TRAIL-induced apoptosis under hypoxic conditions by activating MEF2A.Experimental cell research, 2025 · PMID 39581216
  7. MOTS-c attenuates lung ischemia-reperfusion injury via MYH9-Dependent nuclear translocation and transcriptional activation of antioxidant genes.Redox biology, 2025 · PMID 40403491
  8. A mitochondrial-derived peptide MOTS-c contributes to the protective effect against brain injury associated with LPS-induced sepsis by strengthening the blood-brain barrier's ultrastructure.The International journal of neuroscience, 2025 · PMID 40753494
  9. MOTS-c attenuates airway barrier dysfunction in allergic asthma by inhibiting epithelial apoptosis via Nrf2 pathway.International immunopharmacology, 2025 · PMID 40472776
  10. MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 Pathway to Ameliorate Cardiopulmonary Bypass-induced Lung Injury.American journal of respiratory cell and molecular biology, 2025 · PMID 40035775
  11. A Mighty Mitochondrial Microprotein: The Protective Role of MOTS-c in Acute Lung Injury.American journal of respiratory cell and molecular biology, 2025 · PMID 40072017
  12. MOTS-c mimics exercise to combat diabetic liver fibrosis by targeting Keap1-Nrf2-Smad2/3.Scientific reports, 2025 · PMID 40425777
  13. Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.American journal of physiology. Endocrinology and metabolism, 2024 · PMID 38170165
  14. The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study.Blood purification, 2024 · PMID 39111290
  15. MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis.Acta biochimica et biophysica Sinica, 2024 · PMID 38716540
  16. Expression Patterns of MOTS-c in Adrenal Tumors: Results from a Preliminary Study.International journal of molecular sciences, 2024 · PMID 39201408
  17. Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024 · PMID 39321430
  18. Neuroprotective Mechanism of MOTS-c in TBI Mice: Insights from Integrated Transcriptomic and Metabolomic Analyses.Drug design, development and therapy, 2024 · PMID 39050800
  19. Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial biogenesis.Molecular pain, 2024 · PMID 38658141
  20. The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression.Cell reports, 2024 · PMID 38206815
  21. The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis.Diabetology & metabolic syndrome, 2024 · PMID 39160573
  22. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related DiseasesDiabetes Metab J, 2023 · PMID 36824008
  23. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and agingMol Cell Biochem, 2023 · PMID 36670507
  24. The protective effect of the mitochondrial-derived peptide MOTS-c on LPS-induced septic cardiomyopathy.Acta biochimica et biophysica Sinica, 2023 · PMID 36786072
  25. MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake-A Preliminary Study.International journal of molecular sciences, 2023 · PMID 37834399
  26. Orally administered MOTS-c analogue ameliorates dextran sulfate sodium-induced colitis by inhibiting inflammation and apoptosis.European journal of pharmacology, 2023 · PMID 36528071
  27. MOTS-c and aerobic exercise induce cardiac physiological adaptation via NRG1/ErbB4/CEBPβ modification in rats.Life sciences, 2023 · PMID 36584915
  28. The mitochondrial-derived peptide MOTS-c suppresses ferroptosis and alleviates acute lung injury induced by myocardial ischemia reperfusion via PPARγ signaling pathway.European journal of pharmacology, 2023 · PMID 37290680
  29. The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury.Scientific reports, 2023 · PMID 37957221
  30. Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study.Frontiers in medicine, 2023 · PMID 36844198
  31. The Mitochondrial-Derived Peptide (MOTS-c) Interacted with Nrf2 to Defend the Antioxidant System to Protect Dopaminergic Neurons Against Rotenone Exposure.Molecular neurobiology, 2023 · PMID 37380822
  32. Adropin and MOTS-c as new peptides: Do levels change in neurodegenerative diseases and ischemic stroke?Journal of biochemical and molecular toxicology, 2023 · PMID 36303331
  33. Serum MOTS-C Levels are Decreased in Obese Children and Associated with Vascular Endothelial Function.Diabetes, metabolic syndrome and obesity : targets and therapy, 2023 · PMID 37077579
  34. Mitochondrial-Derived Peptide MOTS-c Ameliorates Spared Nerve Injury-Induced Neuropathic Pain in Mice by Inhibiting Microglia Activation and Neuronal Oxidative Damage in the Spinal Cord via the AMPK Pathway.ACS chemical neuroscience, 2023 · PMID 37285113
  35. MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria.Mitochondrion, 2023 · PMID 37307934
  36. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related DiseasesInt J Mol Sci, 2022 · PMID 36233287
  37. The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance.Biochimica et biophysica acta. General subjects, 2022 · PMID 34728329
  38. MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose.Physiological reports, 2022 · PMID 35808870
  39. MOTS-c promotes muscle differentiation in vitro.Peptides, 2022 · PMID 35842023
  40. The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.Pharmacological research, 2022 · PMID 34798268
  41. The Mitochondrial-Derived Peptide MOTS-c Attenuates Oxidative Stress Injury and the Inflammatory Response of H9c2 Cells Through the Nrf2/ARE and NF-κB Pathways.Cardiovascular engineering and technology, 2022 · PMID 34859377
  42. MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats.Frontiers in endocrinology, 2022 · PMID 35370955
  43. Mitochondrial derived peptide MOTS-c prevents the development of heart failure under pressure overload conditions in mice.Journal of cellular and molecular medicine, 2022 · PMID 36156853
  44. MOTS-c repairs myocardial damage by inhibiting the CCN1/ERK1/2/EGR1 pathway in diabetic rats.Frontiers in nutrition, 2022 · PMID 36687680
  45. Circulating levels of MOTS-c in patients with breast cancer treated with metformin.Aging, 2022 · PMID 36490309
  46. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasisNat Commun, 2021 · PMID 33462442
  47. MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathwayBiochim Biophys Acta Gen Subj, 2021 · PMID 33722744
  48. MOTS-c reduces myostatin and muscle atrophy signalingAm J Physiol Endocrinol Metab, 2021 · PMID 33261060
  49. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.Nature communications, 2021 · PMID 33473109
  50. MOTS-c reduces myostatin and muscle atrophy signaling.American journal of physiology. Endocrinology and metabolism, 2021 · PMID 33554779
  51. Relationship between the mitochondria-derived peptide MOTS-c and insulin resistance in obstructive sleep apnea.Sleep & breathing = Schlaf & Atmung, 2021 · PMID 33394327
  52. Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.Cell reports, 2021 · PMID 34320351
  53. The mitochondrial signaling peptide MOTS-c improves myocardial performance during exercise training in rats.Scientific reports, 2021 · PMID 34635713
  54. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors.Scientific reports, 2021 · PMID 34413391
  55. Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition.Aging, 2020 · PMID 32182209
  56. Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1-SIRT1-PGC-1α.Diabetologia, 2020 · PMID 32880686
  57. Mitochondrial-Derived Peptide MOTS-c Attenuates Vascular Calcification and Secondary Myocardial Remodeling via Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway.Cardiorenal medicine, 2020 · PMID 31694019
  58. The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivityPhysiol Rep, 2019 · PMID 31311755
  59. MOTS-c: an equal opportunity insulin sensitizerJ Mol Med (Berl), 2019 · PMID 30648975
  60. MOTS-c improves osteoporosis by promoting the synthesis of type I collagen in osteoblasts via TGF-β/SMAD signaling pathway.European review for medical and pharmacological sciences, 2019 · PMID 31081069
  61. MOTS-c accelerates bone fracture healing by stimulating osteogenesis of bone marrow mesenchymal stem cells via positively regulating FOXF1 to activate the TGF-β pathway.European review for medical and pharmacological sciences, 2019 · PMID 31858528
  62. MOTS-c: an equal opportunity insulin sensitizer.Journal of molecular medicine (Berlin, Germany), 2019 · PMID 30788534
  63. Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects.Clinical endocrinology, 2019 · PMID 31066084
  64. The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity.Physiological reports, 2019 · PMID 31293078
  65. MOTS-c inhibits Osteolysis in the Mouse Calvaria by affecting osteocyte-osteoclast crosstalk and inhibiting inflammation.Pharmacological research, 2019 · PMID 31369811
  66. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistancePediatr Diabetes, 2018 · PMID 29691953
  67. Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individualsJ Investig Med, 2018 · PMID 29593067
  68. Mitochondrial-Derived Peptides Exacerbate Senescence.Rejuvenation research, 2018 · PMID 30058454
  69. MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA.Molecular immunology, 2017 · PMID 29096170
  70. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism.Free radical biology & medicine, 2016 · PMID 27216708
  71. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation.Biochemical and biophysical research communications, 2016 · PMID 27237975
  72. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistanceCell Metab, 2015 · PMID 25738459
  73. The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity?Aging cell, 2015 · PMID 26289118