MOTS-c Benefits and Research Applications

MOTS-c is a mitochondrial-derived oligopeptide that has gained considerable research interest thanks to its potential impact on metabolic well-being and longevity.

Potential MOTS-c benefits are quite numerous and include:

• Anti-obesity effects
• Anti-aging effects
• Cardioprotection
• Neuroprotection
• Muscle performance enhancement
• Improving cellular stress response

In this article, we explore MOTS-c benefits and safety to provide a starting point for researchers wishing to study the compound.

Plus, we include our top recommendation of where to source research-grade MOTS-c online.

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What is MOTS-c?

The origins of MOTS-c can be traced back to the exploration of mitochondrial DNA and its impact on metabolic health and longevity. Since its discovery in 2015, MOTS-c has garnered attention for its potential role in metabolic regulation and age-related health [1].

In subsequent investigations, researchers have demonstrated the impact of MOTS-c on energy metabolism, insulin sensitivity, and the cellular stress response [2, 3].

MOTS-c research is now focused on applications like combating metabolic disorders such as obesity and type 2 diabetes [4]. Researchers are also exploring its role in enhancing physical performance and its anti-aging properties, offering a promising avenue for research [5].

The compound is still in the early stages of research. Regulatory bodies are carefully evaluating its safety, efficacy, and potential side effects to ensure responsible use in future medical interventions [6].

An analog of MOTS-c known as CB4211 is currently undergoing evaluation for clinical use in both healthy subjects and those with nonalcoholic fatty liver disease (NFLD), with phase 1a clinical trials having been completed in 2021 [7].

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What Does MOTS-c Do?

MOTS-c, or Mitochondrial Open Reading Frame of the 12S rRNA Type-c, is a peptide derived from the mitochondrial genome [8].

Chemically, MOTS-c is composed of 16 amino acids and shares structural similarities with other peptides involved in metabolic regulation, such as Humanin and SHLP2. Its specific amino acid sequence is MRWQEMGYIFYPRKLR [8].

The precise mechanism by which MOTS-c works is not yet fully understood. However, it is believed to operate by activating the AMP-activated protein kinase (AMPK) pathway, which is a crucial regulator of cellular energy balance and is involved in glucose and lipid metabolism [9].

During stress conditions, MOTS-c notably undergoes translocation to the nucleus, where it plays a regulatory role in a diverse set of genes involved in metabolic dysfunction. This nuclear localization highlights its involvement in modulating gene expression under stressful metabolic conditions [2].

MOTS-c’s activation of AMPK leads to several beneficial effects, including enhanced glucose uptake, improved mitochondrial function, and increased insulin sensitivity [9]. These effects suggest that MOTS-c holds potential applications in the treatment of metabolic disorders like type 2 diabetes and obesity [4].

Regarding its pharmacokinetics, MOTS-c is known to be relatively stable and capable of circulating in the bloodstream. While MOTS-c is commonly found in mitochondria in different tissues and can also be detected in plasma, its levels decline as individuals age [2].

In addition to its metabolic effects, MOTS-c has been known to exhibit neuroprotective properties. It may help protect neurons against oxidative stress and promote neuronal survival [10].

Further, it has shown promising results in animal studies for halting age-related diseases like osteoporosis, muscular atrophy, postmenopausal disorders, and Alzheimer’s [4, 7].

MOTS-c, in its entirety, has good prospects for therapeutic applications given its effects on metabolic and age-related disorders [10]. Nevertheless, more scientific research is needed to assess the potential scope of its clinical use.

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Benefits of MOTS-c | A Comprehensive Review

MOTS-c has shown various benefits in preclinical studies. While more research is needed to fully understand its therapeutic applications, here are some potential benefits associated with MOTS-c.

MOTS-c for Obesity & Metabolic Disorders

A study conducted by Lee et al. (2015), carried out experiments on mice to investigate the effects of MOTS-c on weight management. The researchers fed one group of mice a high-fat diet while injecting them with MOTS-c intraperitoneally (into the abdominal cavity) daily for eight weeks. Another group of mice was injected with MOTS-c but fed a normal diet [11].

The results of the study were eye-opening. The mice that were injected with MOTS-c and fed a regular diet did not exhibit any significant weight reduction. However, the mice that received MOTS-c injections alongside a high-fat diet showed a remarkable decrease in body weight.

This study suggests that MOTS-c may potentially play a role in weight management. Yet, the specific mechanisms through which MOTS-c influences weight reduction in the context of a high-fat diet are still unknown and require further investigation [11].

In another study by Lu et al. (2019), it was found that the postmenopausal state increases the risk of metabolic disorders, such as reduced energy expenditure, weight gain, and higher risks of cardiovascular and cancer-related diseases [12].

The study demonstrated that MOTS-c treatment in mice prevented obesity and insulin resistance caused by ovariectomy (removal of ovaries). Moreover, MOTS-c was found to activate brown fat, reduce fat accumulation, and decrease inflammation in white adipose tissue. This led to lower levels of fatty acids in the blood and liver [12].

MOTS-c has also been shown to improve insulin sensitivity, increase glucose uptake in peripheral tissues, and regulate energy metabolism, making it a target for treating metabolic disorders like type 2 diabetes and obesity [4, 12].

MOTS-c for Anti-Aging

MOTS-c, a peptide whose levels decrease as individuals age, has been found to have various implications for healthspan.

In studies by Reynolds et al. (2021) on mice, it was observed that intraperitoneal administration of MOTS-c at a dosage of 15 mg/kg/day resulted in enhanced physical performance in mice of different age groups (2, 12, 22, and 23.5 months) for two weeks. This treatment not only improved their physical capabilities but also delayed the onset of age-related declines [5].

Further, the loss of dermal collagen is a significant contributor to the aged appearance of the skin, characterized by a flattened dermo-epidermal interface and disorganized extracellular matrix [13].

Li et al. (2019) found that MOTS-c increased levels of skin collagen when administered via intraperitoneal injection at a dose of 10 mg/kg in 6-week-old mice. This increase was attributed to MOTS-c's ability to reduce levels of IL-6, a key inflammatory factor that contributes to the degradation of collagen by matrix metalloproteinase 1 (MMP1) in the dermis. By reducing inflammation, MOTS-c has the potential to prevent skin aging and promote the production of dermal collagen [14].

MOTS-c for Cardiovascular Function

In a study by Quing Quin et al. (2018), 40 patients undergoing coronary angiography and endothelial function testing were divided into two groups based on their response to intracoronary acetylcholine (ACh): normal endothelial function and endothelial dysfunction (ED) groups (n=20 each).

Aortic plasma samples were collected and analyzed for MOTS-c levels.The baseline parameters of both the test and control groups were similar. Patients with ED had lower levels of MOTS-c in their plasma compared to those with normal endothelial function [15].

In an animal study by Zhong et al. (2022), a heart failure mouse model was created using transverse aortic constriction (TAC) surgeries. MOTS-c peptide was administered subcutaneously via an osmotic pump. Echocardiography was performed to evaluate cardiac function and heart tissues were analyzed histologically and molecularly.

Strikingly, MOTS-c peptide was found to mitigate TAC-induced cardiac dysfunction and remodeling. It also reduced inflammatory response, enhanced antioxidant capacity, and activated the AMPK pathway in the hearts of the TAC mouse model [16].

MOTS-c for Neuroprotection

In Alzheimer’s disease, damaged mitochondria generate reactive free radicals, leading to oxidative stress, cell death, and cognitive impairments.

Jiang et al. (2021) demonstrated that MOTS-c therapy improved the formation of object and location recognition memories. This improvement was achieved by phosphorylating AMPK, reducing the activation of astrocytes and microglia, and decreasing the production of proinflammatory cytokines [10].

MOTS-c for Muscle Performance

Previous studies have indicated that MOTS-c naturally targets muscle tissue, accelerating skeletal muscle metabolism and energy production [4, 17].
Ran et al. (2021) showed that MOTS-c enhances glycolysis and increases ATP levels in dystrophic muscle cells, improving the uptake and effectiveness of phosphorodiamidate morpholino oligomer. Further, long-term combined administration of MOTS-c and phosphorodiamidate morpholino oligomer in mice affected by Duchenne muscular dystrophy (DMD) resulted in significant improvement in muscular functions [17].

MOTS-c for Immunity

Type 1 diabetes (T1D) is an autoimmune disorder characterized by the destruction of pancreatic β-cells, resulting in inadequate insulin production. In studies conducted by Kong et al. (2021), MOTS-c demonstrated the potential to prevent the autoimmune destruction of β-cells by targeting T cells in non-obese diabetic mice [18].

The administration of MOTS-c in these mice regulated the phenotype and function of T cells by inhibiting TCR/mTORC1 signaling. Consequently, MOTS-c effectively improved hyperglycemia and reduced immune cell infiltration in the islets [18].

These findings suggest that MOTS-c has suppressive effects on autoimmune diabetes, potentially delaying the onset of T1D and serving as an early preventive measure.

MOTS-c for Inflammation Modulation

MOTS-c has shown promise for treating inflammation-related disorders. In experiments conducted by Shen et al. (2021), it was observed that MOTS-c protected rat cardiomyocytes from inflammation and oxidative stress induced by hydrogen peroxide. This protective effect was achieved by suppressing NF-κB (a key regulator of inflammation) and activating the Nrf2-ARE pathway (a pathway involved in antioxidant defense) [19].

MOTS-c for Bone Metabolism

The imbalance between the synthesis and absorption of inorganic minerals and organic matrices, particularly Type I collagen, is a key factor in osteoporosis.

A study by Che et al. (2019), revealed that when hFOB1.19 cells (Human Fatal Osteoblastic cells) were treated with MOTS-c, there was an observed increase in the expression levels of TGF-β, SMAD7, and COL1A2 at both the mRNA and protein levels. These findings indicate that MOTS-c stimulated osteoblasts to produce type I collagen through the TGF-β/SMAD pathway [20].

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MOTS-c Side Effects and Safety

The safety profile of MOTS-c is still under investigation as it is still a relatively new compound.

So far, no significant adverse effects have been reported in the studies conducted. Animal studies and in vitro experiments have demonstrated the positive effects of MOTS-c on various health parameters without apparent toxicity [5, 11, 12].

Further research is needed to thoroughly assess the long-term safety and potential side effects of MOTS-c in human subjects.

Nevertheless, biotechnology firm CohBar has shared important findings from a clinical study on a molecule called CB4211 (MOTS-c analog). CB4211 is being developed to help people with nonalcoholic steatohepatitis (NASH) and obesity. The study involved multiple centers and used a randomized, double-blind, and placebo-controlled approach. The results showed that CB4211 was well-tolerated and seemed safe, with no significant adverse effects [21].

Researchers should always note the possibility of side effects associated with peptide injections. Potential side effects of MOTS-c injections may include:

• Irritation at the site of injection
• Swelling or redness
• Formation of nodules or lumps
• Pain or discomfort during or after injection
• Bruising or discoloration
• Allergic reactions, such as hives or difficulty breathing (rare but possible)

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Where to Buy MOTS-c Online? | 2024 Edition

Growing research interest in MOTS-c has increased the compound’s availability through online sources.

To ensure safety and accuracy in experimentation, researchers should source the compound strictly from a reputable and trustworthy vendor.

The Peptides.org team has reviewed several vendors and confidently endorses the following two.

Limitless Life

Limitless Life is our preferred choice for purchasing MOTS-c for these reasons:

• Top-Quality MOTS-c: Limitless Life’s MOTS-c is produced in regulated American laboratories and quality tested by a third party using HPLC-MS analysis.
• User-Friendly Website: The vendor’s user-friendly online platform makes it easy to navigate through their product selection and place orders. Customers can find detailed product information at this vendor’s website.
• Smooth Checkout: The vendor accommodates a range of payments including credit cards, eCheck, and Cash App, and even waives the shipping fee on orders of $350+.
• Fantastic Support: Limitless Life customer service representatives are always available by email and phone to address any pressing queries related to the vendor’s products or the shipping process.

Limitless Life is currently extending a 10% discount to first-time customers. Just enter this code at checkout:

peptidesorg10

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Xcel Peptides

Researchers may also visit Xcel Peptides for high-purity MOTS-c. This US-based vendor earns top marks for the following features:

• Reliable and Reputable Supplier: While they’re new to the scene, Xcel Peptides is a reliable and reputable supplier of high-quality peptides. Their reputation is supported by numerous five-star customer reviews that establish them as a trusted source in the industry.
• Authentic and Pure Products: Xcel Peptides guarantees the delivery of genuine and pure MOTS-c to their customers. They place a strong emphasis on product quality and adhere to stringent industry standards. All peptides are subjected to rigorous third-party lab testing to ensure authenticity, purity, and quality.
• Excellent Support and Service: Xcel Peptides values researcher satisfaction and provides excellent service and support. Their responsive team is readily available to address any inquiries or concerns throughout the purchasing process.

And that’s not all! Researchers get a 10% discount off their first order by joining the Xcel Peptides email newsletter below:

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How to Reconstitute MOTS-c

MOTS-c is available in lyophilized powder form and is shipped in vials. The vials may vary in size and can range from 5mg to 10mg, depending on the supplier and product specifications. The vials are sealed with a rubber stopper to maintain the integrity of the peptide powder.

To reconstitute MOTS-c, follow these steps:

• Gather the necessary materials: MOTS-c vial, bacteriostatic water, sterile syringe, and alcohol swabs.
• Prepare the syringe by attaching a sterile needle and drawing air into it.
• Wipe the rubber stopper of the MOTS-c vial with an alcohol swab to disinfect it.
• Inject the air from the syringe into the vial by piercing the rubber stopper.
• Slowly withdraw the desired volume of bacteriostatic water into the syringe.
• Insert the syringe with the water into the vial, piercing the rubber stopper.
• Gently inject the bacteriostatic water into the vial.
• Swirl the vial gently to aid dissolution, but avoid vigorous shaking.
• Inspect the solution in the vial for clarity and ensure there are no visible particles present.

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Benefits of MOTS-c | Verdict

At present, MOTS-c is recognized as a research peptide and is not an approved therapeutic agent. Human trials are indispensable for establishing optimal dosage, routes of administration, and potential side effects of MOTS-c in diverse patient populations.

MOTS-c offers a range of potential benefits, including addressing obesity and metabolic disorders, promoting anti-aging effects, supporting cardiovascular function and neuroprotection, enhancing muscle performance, boosting immunity, modulating inflammation, and potentially aiding in the prevention of osteoporosis.

Although the initial results of MOTS-c are promising, it is crucial to conduct comprehensive scientific research before implementing it in clinical practice.

For researchers interested in purchasing MOTS-c for research purposes, we recommend our top-rated vendor.

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