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MOTS-C Peptide: What It Is, Benefits & How It Works

MOTS-c, or Mitochondrial-Derived Peptide MOTS-c, is a relatively recently discovered peptide known for its role in metabolic regulation and potential therapeutic benefits.

It's a short peptide encoded within the mitochondrial DNA, which sets it apart from most other peptides that are encoded in the nuclear DNA.


The benefits of MOTS-c peptide, emerging from its unique mechanism of action, encompass various aspects of health and disease management.

Here's a detailed view of its potential benefits.

1. Obesity & Metabolic Syndrome

By improving insulin sensitivity, MOTS-c helps in better glucose uptake by cells, which is crucial for managing obesity and insulin resistance.

It may aid in the reduction of fat accumulation, particularly visceral fat, which is linked with numerous metabolic disorders. This is similar to how ursolic acid works.

2. Diabetes

MOTS-c's role in stabilizing blood glucose levels is particularly beneficial in managing type 2 diabetes.

Its antioxidative properties may protect against complications like neuropathy and retinopathy.

3. Muscle Health and Performance

MOTS-c can stimulate muscle fiber regeneration, which is beneficial for recovery from muscle injuries and for athletes.

Its role in improving muscle oxidative capacity can lead to enhanced endurance and performance.

4. Aging and Longevity

By supporting mitochondrial health, MOTS-c may counteract some aspects of cellular aging.

Improved metabolic functions and reduced oxidative stress may contribute to increased lifespan and better quality of life in older age.

5. Cardiovascular Health

Improved metabolic health can lead to lower risk of conditions like hypertension and atherosclerosis, contributing to overall cardiovascular health.

6. Neuroprotective Effects

Early research indicates that MOTS-c might have neuroprotective properties, potentially beneficial in neurodegenerative conditions like Alzheimer's disease.

By reducing oxidative stress, it may protect neurons from damage.

7. Anti-inflammatory Properties

MOTS-c might play a role in modulating the inflammatory response, which is beneficial in a wide range of conditions from autoimmune diseases to muscle recovery.

8. Bone Health

Preliminary studies suggest that MOTS-c might influence bone metabolism, potentially helping in the prevention of osteoporosis.

How MOTS-C Works

MOTS-c peptide, a novel mitochondrial-derived peptide, exhibits a multifaceted mechanism of action, influencing various processes primarily related to metabolism, energy regulation, and cellular stress responses.

Its potential impact on various tissues and the whole body makes it a peptide of significant interest in the fields of metabolism, aging, and disease research.

Here's a detailed look at the mechanism of action of MOTS-C.

MOTS-C peptide mechanism of action

1. Mitochondrial Function

The main mechanism of action of MOTS-C is its affects on the mitochondria, the "powerhouse of the cell". It has the following affects.

  • Enhancing Biogenesis: MOTS-c stimulates the production of new mitochondria, enhancing the overall mitochondrial capacity of cells.

  • Improving Efficiency: It enhances the efficiency of the electron transport chain, crucial for ATP production, thereby improving energy generation.

  • Regulating Mitochondrial Dynamics: MOTS-c influences the process of mitochondrial fusion and fission, which is essential for maintaining mitochondrial health and function.

2. Metabolic Regulation

It also has effects on the bodies glucose and metabolic system, such as the following.

  • Insulin Sensitisation: One of the key actions of MOTS-c is its ability to increase insulin sensitivity in peripheral tissues. This means that cells respond more effectively to insulin, facilitating glucose uptake and utilisation.

  • Glucose Homeostasis: By enhancing insulin sensitivity and influencing glucose metabolism pathways, MOTS-c helps in maintaining stable blood glucose levels.

  • Lipid Metabolism: It also affects lipid metabolism, potentially reducing the accumulation of lipids in tissues like liver and muscle, which is beneficial in conditions like fatty liver disease and obesity.

3. Cellular Stress Response

The cellular stress pathways in the body, such as oxidative stress and autophagy, are likely what contributes to the anti-aging potential of this peptide.

  • Oxidative Stress Reduction: MOTS-c has been shown to reduce levels of reactive oxygen species (ROS), which are harmful byproducts of cellular metabolism. This reduction in oxidative stress can protect cells from damage.

  • Enhanced Autophagy: It may promote autophagy, a cellular cleaning process that removes damaged organelles and proteins, thereby contributing to cellular health and longevity.

4. Gene Expression Regulation

MOTS-c can influence the expression of various genes, particularly those involved in metabolism and stress response, altering cellular function in response to metabolic demands.

5. Muscle Fiber Metabolism

In muscle tissue, MOTS-c may enhance the oxidative capacity of muscle fibers, making them more efficient during prolonged exercise.

It may also have other benefits on muscle such as reducing myostatin, improving anabolic signalling, reducing catabolic signalling, etc.

6. Adipose Tissue Function

In adipose (fat) tissue, MOTS-c could influence the way fat is stored and used, potentially contributing to healthier body weight management.

7. Whole-Body Metabolic Effects

Given its role in energy metabolism, MOTS-c potentially exerts systemic effects, improving overall metabolic health, which is beneficial for conditions like metabolic syndrome and type 2 diabetes.

Safety & Research

MOTS-c is still largely in the research phase, with most studies conducted in animal models or in vitro.

While initial results are promising, more comprehensive clinical trials in humans are required to fully understand its safety profile and efficacy.


MOTS-c peptide offers a promising avenue for various health benefits, particularly in the realms of metabolic regulation, aging, and disease management.

However, it's important to note that much of the current knowledge is based on preliminary research, and more in-depth clinical studies are necessary to validate these benefits and ensure safety for human use.


This article provides a general overview of MOTS-c peptide based on current scientific understanding and does not constitute medical advice. For any health-related concerns or decisions regarding the use of peptides, consulting with healthcare professionals is essential.


  1. 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.

  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. doi: 10.3390/ijms231911991. PMID: 36233287; PMCID: PMC9570330. (Review)

  3. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021 Jan 20;12(1):470. doi: 10.1038/s41467-020-20790-0. PMID: 33473109; PMCID: PMC7817689.

  4. Kumagai H, Coelho AR, Wan J, Mehta HH, Yen K, Huang A, Zempo H, Fuku N, Maeda S, Oliveira PJ, Cohen P, Kim SJ. MOTS-c reduces myostatin and muscle atrophy signaling. Am J Physiol Endocrinol Metab. 2021 Apr 1;320(4):E680-E690. doi: 10.1152/ajpendo.00275.2020. Epub 2021 Feb 8. PMID: 33554779; PMCID: PMC8238132.

  5. 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. doi: 10.3390/metabo13010125. PMID: 36677050; PMCID: PMC9866798.

  6. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54. doi: 10.1016/j.cmet.2015.02.009. PMID: 25738459; PMCID: PMC4350682.

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