MOTS-C

MOTSC is a naturally occurring mitochondrial-derived peptide composed of 16 amino acids. It was first identified in 2015 as part of a growing class of small peptides encoded by mitochondrial DNA, rather than nuclear DNA, and has been studied for its role in metabolism, energy regulation, and aging.

Structure and Origin:

MOTSC is encoded by a short open reading frame within the 12S ribosomal RNA gene of mitochondrial DNA.
Its sequence is 16 amino acids long, making it relatively small compared to most proteins, but large enough to have specific biological effects.

Mechanism of Action:

MOTS-C interacts with cellular metabolism, particularly in skeletal muscle and liver cells.
It activates the AMPK pathway (adenosine monophosphate–activated protein kinase), which is a key regulator of energy balance and metabolic homeostasis.
By influencing AMPK, MOTS-C can improve glucose uptake in muscle cells, enhance insulin sensitivity, and regulate lipid metabolism.
It also plays a role in inhibiting the folate-methionine cycle, which can influence cellular stress responses and longevity pathways.

Physiological Effects:

Metabolic Health: MOTS-C has been shown to help lower blood glucose levels and improve insulin sensitivity in animal studies. This makes it a potential target for metabolic disorders like type 2 diabetes.
Fatigue and Energy Regulation: By improving cellular energy metabolism, MOTS-C can enhance exercise capacity and reduce fatigue in animal models.
Anti-Aging Potential: MOTS-C may support healthy aging by promoting mitochondrial function, improving metabolic flexibility, and regulating pathways linked to age-related diseases.
Weight Management: In studies with mice, MOTS-C prevented diet-induced obesity and improved overall metabolic health.

Therapeutic Potential:

Research is still largely preclinical, but MOTS-C has attracted interest as a candidate for therapies targeting metabolic syndrome, diabetes, obesity, and age-related metabolic decline.
Its effects on cellular stress responses also suggest potential in supporting resilience against mitochondrial dysfunction, which is implicated in various chronic diseases.

Pharmacokinetics and Administration:

MOTS-C is typically studied as an injectable peptide in research settings.
Its half-life in circulation is relatively short, necessitating careful dosing considerations in experimental or therapeutic contexts.
Oral bioavailability is very low due to degradation in the gastrointestinal tract.

In summary, MOTS-C is a small but highly influential peptide that bridges mitochondrial function and systemic metabolism, showing promise in managing metabolic disorders and supporting longevity pathways. Its research is still in the early stages, but findings so far suggest it could be a key player in the future of metabolic and anti-aging therapies.

MOTS-C dosing is still largely experimental, as it has not been approved for human therapeutic use. Most available information comes from animal studies and very limited early human research.

1. Animal Studies (Most Common Reference):

Mice are often dosed with MOTS-C at 5–15 mg/kg per day, usually via subcutaneous injection.
Effects observed include improved insulin sensitivity, reduced fat accumulation, and enhanced exercise performance.

2. Human Research (Limited):

Very few human studies exist, and dosing protocols are not standardized.
Some early trials or experimental reports suggest low microgram to milligram ranges per kg body weight, delivered via injection. Exact dosing schedules vary depending on study design.

3. Administration Considerations:

MOTS-C is peptide-based, so it is generally injected subcutaneously rather than taken orally, because it would be broken down in the digestive system.
Frequency in animal studies is usually once or twice daily, depending on the protocol.
There’s no established oral formulation with reliable bioavailability.

4. Safety Notes:

Long-term safety in humans is unknown.
Most information comes from short-term studies in animals.
Dosing in humans should be approached cautiously and only under controlled research settings.