MOTS-c | Reviews, Clinical Studies, and Safety

MOTS-c is a research peptide that shows potential in numerous therapeutic applications. These include the treatment of obesity, metabolic disorders, and cardiovascular disease. It may also enhance athletic performance and provide neuroprotective benefits.

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    Compound Overview

    Class of Compound:


    Mechanism of Action:

    While the precise mechanism of action of MOTS-c is currently under investigation, it is hypothesized that its metabolic effects are mediated through its translocation to the nucleus and subsequent activation of AMPK.

    Notable Studies:

    Also Known As:

    Mitochondrial ORF of the 12S rRNA type-c

    Research Applications:

    • Obesity & metabolic disorders, including insulin resistance
    • Aging-related processes
    • Exercise performance


    • Preclinical stage of development
    • Injection site reactions
    • Many counterfeit products online

    Chemical Structure

    MOTS-c chemical structure

    What is MOTS-c?

    MOTS-c, is a mitochondrial-derived peptide, consisting of 16 residues encoded by the 12S rRNA region of the mitochondrial genome [4, 16]. This means that the genetic information that is translated into the peptide’s amino acid sequence has not been processed into a strip of mRNA. Rather, the peptide is translated from a strand of rRNA whose main role is not to carry genetic information but to help ribosomes work in processing such information [17] . MOTS-cwas discovered in 2015 and has since attracted attention for its potential role in metabolic regulation and age-related conditions [1].

    MOTS-c has been found to have various effects on cellular metabolism, insulin sensitivity, mitochondrial function, and aging processes [2, 3].

    Studies suggest that MOTS-c may [16]:

    • Improve glucose uptake and utilization
    • Enhance insulin sensitivity
    • Promote mitochondrial biogenesis (the formation of new mitochondria)
    • Reduce oxidative stress

    These effects may contribute to improved metabolic health and cellular function, with potential implications for the management of diabetes, obesity, and age-related diseases [2, 3].


    What Does MOTS-c Do?

    In a study by Kim et al. (2018), it was demonstrated that MOTS-c can translocate to the nucleus in response to metabolic stress. This translocation allows MOTS-c to modulate adaptive gene expression in the nucleus [4].

    MOTS-c is also referred to as a "mitochondria hormone" or "mitokine" due to its release into the bloodstream. Along with humanin, MOTS-c is one of the more extensively studied mitochondrial-derived peptides (MDPs). While humanin can bind to various receptors, no specific receptors have been identified for MOTS-c [5].

    The circulation of MOTS-c is regulated in part by the folate cycle, and its expression is influenced by age. Studies show that endogenous levels of this peptide tend to decline as individuals grow older [5].

    Under conditions of stress, MOTS-c undergoes translocation from the mitochondria to the nucleus. Through this mechanism, MOTS-c modulates levels of the enzymes known as activated protein kinase (AMPK) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), both essential regulators of energy homeostasis [6, 7].

    Overall, MOTS-c serves as a key mediator of metabolic functions. In this capacity, it has shown the potential to address metabolic disorders such as postmenopausal insulin resistance and obesity. Studies also suggest anti-aging outcomes enacted through distinct age-related pathways, as well as cardiometabolic benefits attributed to its role in cellular energy homeostasis [8, 9].

    Further research is needed to fully understand the intricate mechanisms by which MOTS-c modulates cellular metabolism and its potential implications for various physiological and pathological conditions.

    MOTS-c Benefits | Clinical Trials

    MOTS-c has demonstrated promise in preclinical studies, suggesting several potential benefits. Although further research is required to fully understand its therapeutic applications, here are some of the potential benefits associated with MOTS-c per findings to date:

    MOTS-c for metabolic disorders: Postmenopausal women often experience hormonal changes that can lead to metabolic dysfunction and an increased risk of conditions such as obesity and impaired insulin sensitivity. A study conducted by Lu et al. (2019) investigated the effects of MOTS-c treatment on these metabolic changes in mice that underwent ovariectomy.

    The study found that ovariectomy resulted in increased fat mass and disrupted adipose tissue function, leading to insulin resistance. However, MOTS-c treatment prevented the development of obesity and insulin resistance. The treatment was also associated with the activation of brown fat, reduced adiposity, and lowered inflammation, ultimately resulting in decreased levels of fatty acids in the blood and liver [8].

    These findings suggest that MOTS-c has the potential to mitigate the metabolic changes observed in postmenopausal women and prevent the development of obesity and insulin resistance.

    MOTS-c for obesity: In a study conducted by Lee et al. (2015), researchers aimed to investigate the effects of MOTS-c on weight management in mouse models. Mice that received daily MOTS-c injections alongside a high-fat diet exhibited a significant decrease in body weight compared to mice that received MOTS-c injections with a regular diet. There was no significant weight reduction observed in the latter [1].

    These findings indicate that MOTS-c may have implications for weight management, particularly in the context of high-fat diets. However, the specific mechanisms by which MOTS-c influences weight reduction in conjunction with high fat intake are not fully understood and require further investigation. It is important to note that these laboratory animal study findings cannot be extrapolated to human subjects.

    MOTS-c for anti-aging:Aging is a complex process characterized by the gradual deterioration of biological functions and an impaired ability to respond to metabolic stress. This phenomenon, known as senescence, can be mitigated by enhancing mitochondrial fitness and physical capacity, which contribute to healthy aging.

    MOTS-c levels are observed to decline in individuals aged 70-81, showing a decrease of approximately 21% compared to younger individuals aged 18-30. MOTS-c is also shown to share metabolic pathways with age-related modifiers, such as NAD+, a critical modulator of cellular signaling and survival pathways [9].

    In one murine study conducted by Reynolds et al. (2021), MOTS-c improved physical performance and reduced age-related declines across multiple age groups over a two-week period of daily administration. These findings highlight the potential of MOTS-c as a therapeutic target in promoting healthy aging and preventing age-related diseases [6].

    MOTS-c for cardiovascular function:Vascular calcification (VC) is the abnormal accumulation of calcium phosphate crystals in arterial walls, occurring as a complication of chronic kidney disease and atherosclerosis. A laboratory animal study on MOTS-c therapy for vascular calcification revealed that MOTS-c effectively prevented vascular calcification.

    This beneficial effect was attributed to the peptide’s activation of AMPK signaling. However, further research is necessary to determine the clinical relevance of these findings in human subjects [10, 11].

    MOTS-c for enhanced muscle performance: During exercise, mitochondria play a crucial role in supporting skeletal muscle function and transmitting exercise-induced signals to other organs. MOTS-c, along with exercise training, has been shown to have an additive effect on boosting the expression of the PGC-1α gene, which is involved in mitochondrial biogenesis and energy metabolism [12].

    In mice, treatment with MOTS-c has been found to activate skeletal muscle AMPK, a regulator of exercise response, by increasing cellular levels of AICAR (an AMPK agonist) and GLUT4 [13]. In a study conducted by Li et al. (2022), it was observed that MOTS-c therapy and regular aerobic exercise led to alterations in pathogenic genes, with overlapping effects on 24 genes related to angiogenesis, inflammation, and apoptosis [14].

    Overall, the evidence indicates that MOTS-c and exercise share common pathways in improving mitochondrial function, and energy metabolism.

    This is not an exhaustive review of the numerous suggested benefits of MOTS-c peptide therapy in ongoing clinical analysis. Researchers are advised to keep up to date on emerging findings regarding this cutting-edge compound.

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    MOTS-c Side Effects

    To date, no significant adverse side effects have been reported in studies on MOTS-c. Laboratory animal studies and in vitro experiments have demonstrated the beneficial effects of MOTS-c on various health parameters without apparent toxicity [6, 8].

    However, further research is necessary to thoroughly assess the long-term safety and potential side effects of MOTS-c in human subjects.

    CohBar, a biotechnology company, conducted a clinical study focusing on CB4211, an analog of MOTS-c, for individuals with nonalcoholic steatohepatitis (NASH) and obesity. The results revealed that CB4211 was well-tolerated and appeared to be safe, with no significant adverse effects reported [15].

    These findings provide valuable insights into the safety profile of MOTS-c analogs and their potential therapeutic applications.

    As an injectable peptide, MOTS-c carries the potential for certain adverse effects, including:

    • Irritation at the site of injection
    • Swelling or redness around the injection site
    • Formation of nodules or lumps at the injection site
    • Pain or discomfort during or after injection
    • Bruising or discoloration at the injection site
    • Rare allergic reactions, such as hives or difficulty breathing

    To minimize the risk of adverse effects, researchers are advised to purchase MOTS-c from a legitimate source and employ aseptic handling techniques in all laboratory procedures.

    Is MOTS-c Safe?

    The safety of MOTS-c is still under investigation as it is a relatively new compound. So far, there have been no significant adverse side effects reported [6, 8].

    Nonetheless, researchers must thoroughly familiarize themselves with all relevant clinical data on the potential risks of experimental MOTS-c administration.

    This peptide must be handled by strictly qualified researchers and laboratory professionals. Under no circumstances is it suitable for self-administration outside of scientific research contexts.

    MOTS-c Dosing Protocol

    Dosing and cycling protocols for MOTS-c may vary depending on the specific research objective and individual factors. It is important to note that MOTS-c is still being studied, and there is no standardized dosing protocol established. Studies to date tend to employ subcutaneous injection as the route of administration.

    Although MOTS-c is generally considered safe, individual reactions may vary [6, 8]. Researchers must refer to relevant clinical findings and dosage guidelines, adjusting as necessary per the subject's tolerance level.

    Sample MOTS-c Dosing Protocol

    Here is a sample dosing protocol that researchers may reference for studies on MOTS-c and obesity.

    • MOTS-c Dosage: 5mg of MOTS-c via subcutaneous injection in the morning
    • Frequency: Every 5 days
    • Duration: 20 days
    • Cycle: Repeat this cycle six months after completion of the first course.
    • Notes: Lifestyle modifications for weight management should also be employed, including a healthy diet, regular exercise, and proper sleep.
    • Supply: Researchers will need two 10mg vials of MOTS-c to complete one course per this protocol.

    Injections must be performed with aseptic handling protocols. Discontinue the therapy if severe adverse reactions occur.

    Vials of MOTS-c should be safely stored in a cool, dark area and used prior to the date of expiration. For guaranteed peptide purity, purchase all research peptides from sources that comply with leading quality assurance measures.

    Where to Buy MOTS-c Online? | 2024 Edition

    While qualified researchers have a plethora of options from which to source research chemicals like MOTS-c, not all vendors are equal in their quality control processes, pricing, and shipping policies.

    To obtain high-quality MOTS-c, we strongly recommend visiting either of our two preferred retailers.

    Limitless Life

    Limitless Life is our go-to source for research-grade peptides like MOTS-c.

    Here are some reasons why this vendor tops our list:

    • High-Quality MOTS-c: Limitless Life’s MOTS-c is held to high purity standards, verified through HPLC-MS testing by an independent laboratory.
    • Convenient Payments: The vendor accepts a number of convenient payment methods like credit cards, Cash App, and eCheck.
    • User-Friendly Platform: Limitless Life’s website is easy to navigate and facilitates a smooth checkout process. Researchers can find detailed product summaries for any peptide they wish to buy.
    • Researcher-First Approach: The vendor’s amiable service staff is always willing to assist both prospective buyers and current researchers with their questions and concerns.

    As a bonus, Limitless Life is now extending a 10% discount to first-time customers. Simply enter this coupon code when checking out:


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    Xcel Peptides

    Xcel Peptides likewise stocks research-grade MOTS-c, earning our endorsement for these reasons:

    • Quality Assurance: Xcel Peptides subjects of all their peptides, including MOTS-c, to comprehensive third-party lab testing. This rigorous quality control process is implemented to maintain the authenticity, purity, and quality of their peptide products.
    • Peptides Made in the USA: Xcel Peptides oversees all phases of production and partners with USA-based facilities that adhere to Good Manufacturing Practices (GMP).
    • Reliable Shipping: Xcel Peptides ensures safe online shopping along with rapid and reliable deliveries. Domestic orders over $200 are eligible for free shipping and turnaround is always quick.

    But that’s not all! First-time Xcel Peptides customers get a 10% discount by signing up to the vendor’s email newsletter:

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    How to Reconstitute MOTS-c

    MOTS-c is typically available in lyophilized powder form and must be reconstituted using a sterile solvent to enable injection. While sterile water may be used, experts agree that bacteriostatic water is the optimal solvent for extending the shelf-life of the product.

    Bacteriostatic water has a 0.9% benzyl alcohol content, which serves to bar microbial growth. This allows for the safe storage of opened vials for as many as four weeks with refrigeration.

    Meanwhile, sterile water has no preservative content and thus offers no protection against contamination. Even if refrigerated, sterile water solutions must be discarded within 24 hours of reconstitution.

    In contrast, bacteriostatic water solutions refrigerated at 2-8 degrees C (36-46 degrees F) are viable for weeks! Peptide solutions are not suitable for freezing, as this renders them ineffective.

    Materials for Reconstitution

    To properly reconstitute MOTS-c, any research lab should be equipped with these supplies:

    • Vial of quality bacteriostatic water
    • Vial of lyophilized Thymosin Alpha-1 powder
    • Sterile syringe of minimum 3cc
    • Sterile needle (1" 20-gauge)
    • Alcohol wipes
    • Disposable sharps container

    Reconstitution Process

    Here are the steps for MOTS-c reconstitution:

    Step 1: Allow both the peptide and bacteriostatic water vials to reach room temperature before beginning the reconstitution process. They should be stored in a cool area away from sunlight to prevent contamination.

    Step 2: Use an alcohol swab to clean the rubber stopper of both vials to maintain sterility.

    Step 3: Using a syringe, draw the desired amount of bacteriostatic water or sterile saline solution into the syringe. The amount of solution will depend on the concentration and desired dosage of MOTS-c.

    Step 4: Slowly inject the solution into the vial containing the MOTS-c powder. Aim the solution against the inner wall of the vial to avoid excessive foaming. Throw the syringe away in the sharps container.

    Step 5: After adding the solvent, gently swirl the contents to aid in the dissolution of the MOTS-c powder. Do not shake it as this may cause degradation.

    Step 6: After the powder has dissolved, inspect the solution to ensure it is clear and without any visible particles. If researchers notice any particles or discoloration, do not use the solution.

    Step 7: Once reconstituted, the MOTS-c solution can be used immediately or stored according to the manufacturer's instructions. Follow the recommended storage conditions and expiration dates to maintain the stability of the peptide.

    Is MOTS-c Legal?

    In the United States and Europe, the sale of MOTS-c is generally restricted to educational and scientific research purposes only, and it is not intended for human consumption.

    It is crucial to emphasize that purchasing and using MOTS-c should be limited to licensed researchers who are conducting authorized studies.

    Qualified researchers are eligible to buy MOTS-c for study from credible retailers like our top-rated vendor.

    Handlers are cautioned that MOTS-c is not legally authorized for sale as a dietary supplement. The purchase of research peptides illegally marketed as such runs the risk of hazardous side effects due to contaminated and mislabeled products.

    Individuals who do not qualify as legitimate researchers or scientific professionals are advised to refrain from purchasing or handling MOTS-c in the United States according to federal regulations.



    MOTS-c | Reviews

    In conclusion, MOTS-c has shown remarkable potential in various areas of health and wellness. Its unique properties and mechanisms of action make it an attractive molecule for further exploration and potential therapeutic applications.

    With its ability to enhance metabolic function, improve insulin sensitivity, and increase endurance, MOTS-c holds promise as a valuable tool in the fight against metabolic disorders and age-related decline.

    While further research is needed to fully understand the long-term effects and potential applications of MOTS-c, the existing findings suggest a bright future for this peptide. Its multifaceted benefits in metabolic health, mitochondrial function, and exercise performance make it an exciting area of study for scientists and healthcare professionals alike.

    Purchase MOTS-c today from our top-rated vendor, the leader in online research peptide sales.


    1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443–54.
    2. Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci 2022 Oct 9;23(19):11991.
    3. Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023 Jan 13;13(1):125.
    4. Kim, K.H.; Son, J.M.; Benayoun, B.A.; Lee, C. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metab. 2018, 28, 516–524.
    5. Lee, C.; Kim, K.H.; Cohen, P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic. Biol. Med. 2016, 100, 182–187.
    6. Reynolds, J.C.; Lai, R.W.; Woodhead, J.S.; Joly, J.H.; Mitchell, C.J.; Cameron-Smith, D.; Lu, R.; Cohen, P.; Graham, N.A.; Benayoun, B.A.; et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat. Commun. 2021, 12, 1–11.
    7. Zarse, K.; Ristow, M. A mitochondrially encoded hormone ameliorates obesity and insulin resistance. Cell Metab. 2015, 21, 355–356.
    8. Lu H, Wei M, Zhai Y, Li Q, Ye Z, Wang L, Luo W, Chen J, Lu Z. MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med (Berl). 2019 Apr;97(4):473-485.
    9. D’Souza, R.F.; Woodhead, J.S.; Hedges, C.P.; Zeng, N.; Wan, J.; Kumagai, H.; Lee, C.; Cohen, P.; Cameron-Smith, D.; Mitchell, C.J.; et al. Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition. Aging 2020, 12, 5244–5258.
    10. Marulanda, J.; Alqarni, S.; Murshed, M. Mechanisms of vascular calcification and associated diseases. Curr. Pharm. Des. 2014, 20, 5801–5810.
    11. Wei, M.; Gan, L.; Liu, Z.; Liu, L.; Chang, J.R.; Yin, D.C.; Cao, H.L.; Su, X.L.; Smith, W.W. Mitochondrial-derived peptide MOTS-c attenuates vascular calcification and secondary myocardial remodeling via adenosine monophosphate-activated protein kinase signaling pathway. Cardiorenal. Med. 2020, 10, 42–50.
    12. Jäger, S.; Handschin, C.; St-Pierre, J.; Spiegelman, B.M. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc. Natl. Acad. Sci. USA 2007, 104, 12017–12022.
    13. Schnyder, S.; Handschin, C. Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. Bone 2015, 80, 115–125.
    14. Li, S.; Wang, M.; Ma, J.; Pang, X.; Yuan, J.; Pan, Y.; Fu, Y.; Laher, I. MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats. Front Endocrinol. 2022, 13, 812032
    15. BioSpace. (2019, November 05). CohBar completes phase 1a and initiates phase 1b stage of clinical trial for CB4211 under development for NASH and ObesityMilestone for first mitochondrial based therapeutic in humans. BioSpace. Retrieved September 18, 2022, from -initiates-Phase1b-Stage-of-Clinical-Trial-of-CB4211-Under-Development-for-NASH-and-ObesityMilestone-for-First-Mitochondrial-Based-Therapeutic-in-Humans
    16. Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023 Jan 25;14:1120533. doi: 10.3389/fendo.2023.1120533. PMID: 36761202; PMCID: PMC9905433.
    17. Wang, S., Mao, C. & Liu, S. Peptides encoded by noncoding genes: challenges and perspectives. Sig Transduct Target Ther 4, 57 (2019).