MOTS-cLongevity

Mitochondrial peptide studied for metabolism and endurance.

Peptides·Index rating

1/5Speculative

Human data

Safety

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Quick factsat a glance

Status: Research / not approved
Developer: Discovered 2015 (Lee & Cohen, USC; Cell Metabolism)
Receptors / target: Mitochondrial-derived peptide (12S rRNA-encoded); activates AMPK via folate-AICAR one-carbon metabolism and, under stress, translocates to the nucleus to regulate NRF2 antioxidant genes
FDA-approved?: NO
Prescription available?: NO
Studied for: metabolic regulation / insulin sensitivityexercise mimetic / enduranceaging & longevitymitochondrial function

Overview

MOTS-c (Mitochondrial ORF of the 12S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide, first characterized by Lee and colleagues in 2015. It regulates metabolic homeostasis, insulin sensitivity and skeletal-muscle energy metabolism, and is often described as an "exercise mimetic" because endogenous levels rise with physical activity. It is sold strictly as a research chemical: not an approved drug and not evaluated by the FDA, with an evidence base that is overwhelmingly preclinical.

Mechanism

MOTS-c promotes glucose utilization largely by activating the AMPK pathway, in part by interfering with the folate-AICAR one-carbon metabolic cycle, increasing skeletal-muscle glucose uptake and GLUT4 expression. Under metabolic stress (glucose restriction, oxidative stress) it translocates to the nucleus in an AMPK-dependent manner and regulates antioxidant-response genes via stress-responsive transcription factors including NRF2. These mechanisms come from cell and rodent models, not human dosing studies.

Clinical evidence

The evidence base is overwhelmingly preclinical. In mice, MOTS-c administration prevented high-fat-diet- and age-induced insulin resistance, reduced diet-induced obesity, and improved treadmill performance across ages. Human data are limited and observational: exercise raises endogenous muscle and serum MOTS-c, but there are no interventional or dosing trials of exogenous MOTS-c, and a 2023 review confirms no validated clinical application has been developed.

Safety profile

Human safety is essentially unstudied — there are no published interventional human trials, toxicology data or established dosing for exogenous MOTS-c, so its human risk profile is unknown. Pharmacokinetics are poorly characterized and no formal human half-life is established; as a small peptide it is expected to be cleared rapidly. Numeric half-life or dosing figures on vendor sites are not supported by peer-reviewed pharmacokinetic studies. Research use only; nothing here is therapeutic or dosing guidance.

Timelinecommonly reported

No human time-course
There are no interventional human trials of exogenous MOTS-c. Mouse metabolic/endurance effects developed over weeks of dosing; any human timeline is anecdotal.

Reported side effectsreported in literature

Reported in published literature and user reports. Not a complete list, and not medical advice.

Injection-site reactions
Transient energy fluctuations / fatigue
Appetite changes
No completed human safety data

If severe or unexpected symptoms occur, contact a qualified medical professional. PEPTIDES·INDEX does not provide medical advice.

Cautionsdiscuss with a clinician

Use caution or avoid if

Human safety is essentially unstudied, so no contraindications are established; the items below are grounded theoretical cautions only.
Diabetes or use of glucose-lowering therapy, given MOTS-c's effects on AMPK and glucose uptake could in theory influence blood glucose.
Any condition where an unknown human safety profile is unacceptable, since there are no toxicology or long-term human data.

Interactions

Glucose-lowering agents (insulin, metformin)Theoretical additive effect on glucose handling via AMPK/glucose-uptake activity; not characterized in humans (research use only)
Other agentsNo documented human drug interactions; uncharacterized in humans (research use only)

Compare

vs NAD+
Another metabolic/longevity-oriented research compound often discussed alongside MOTS-c.
vs 5-Amino-1MQ
A metabolic research compound in the same energy/longevity space.

FAQ

Are there any human trials of MOTS-c?

No interventional or dosing trials of exogenous MOTS-c exist. The evidence base is overwhelmingly preclinical (cell and mouse models); human data are limited to observational findings that exercise raises endogenous MOTS-c.

What is MOTS-c thought to do?

In cell and rodent models it activates the AMPK pathway, increases skeletal-muscle glucose uptake, and under stress regulates antioxidant-response genes via NRF2. It is often called an exercise mimetic, but these mechanisms have not been confirmed in human dosing studies.

Is MOTS-c banned in sport?

MOTS-c is not currently named on the WADA Prohibited List. Status can change, so anyone subject to testing should verify the current list, and it remains research-use-only.

What kind of peptide is MOTS-c?

MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA gene, first characterized by Lee and colleagues in 2015. That mitochondrial origin distinguishes it from the nucleus-encoded GHRH and ghrelin peptides, and it acts as a metabolic regulator rather than a growth-hormone secretagogue.

Is there an established half-life or dosing for MOTS-c?

No. There is no formal human pharmacokinetic data and no validated human dosing; as a small peptide it is expected to clear rapidly. Numeric half-life or dosing figures shown on vendor sites are not supported by peer-reviewed pharmacokinetic studies, and any reported protocol is anecdotal.

What did the mouse studies of MOTS-c actually show?

In mice, MOTS-c administration prevented high-fat-diet- and age-induced insulin resistance, reduced diet-induced obesity, and improved treadmill performance across ages. These are rodent findings; a 2023 review confirms no validated clinical application has been developed in humans.

Similar compounds

NAD+LongevityCoenzyme studied for cellular energy and longevity.5-Amino-1MQWeight Loss / GLP-1NNMT inhibitor studied for fat metabolism and energy.

Sources

Starting references for the library summary. These are not dosing instructions or medical advice.

The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistanceCell Metabolismpubmed.ncbi.nlm.nih.gov/25738459/…The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic StressCell Metabolismpubmed.ncbi.nlm.nih.gov/29983246/…MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasisNature Communicationspubmed.ncbi.nlm.nih.gov/33473109/…MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitationFrontiers in Endocrinologypubmed.ncbi.nlm.nih.gov/36761202/…

For research-use educational context only. Not medical advice and not a recommendation to use any compound. Consult a qualified healthcare professional before any health decision.