MOTS-c
Longevity & Cellular Aging
CAS
1627580-64-6
Molecular Weight
2174
Da
Animal / In Vitro
A 16 amino acid peptide with one of the most unusual origins of any compound in this catalog, it is encoded by mitochondrial DNA rather than nuclear DNA, making it a mitochondrial-derived peptide (MDP). Discovered in 2015 by researchers at the USC Davis School of Gerontology, MOTS-c is produced naturally in the body and its levels decline with age and increase in response to exercise. Studied for metabolic regulation, insulin sensitivity, obesity, longevity, and cardiovascular protection. Considered an exercise mimetic. No human clinical trials completed. Research compound only.
Injectable
Intranasal Suitable
No
Research Compound
Community Signal
Community signal remains sparse, MOTS-c is discussed primarily in longevity and mitochondrial health forums rather than mainstream biohacking communities. Interest is growing following animal research publications, but most discussion remains research-adjacent rather than personal experience reports. Users who do report personal use typically frame it as an exercise mimetic or metabolic compound, often stacking with other mitochondrial-focused peptides. Energy and exercise recovery are the most frequently cited subjective effects. The compound's mitochondrial origin story resonates with longevity-focused communities interested in the hallmarks of aging framework.
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What It Is
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is encoded within the 12S rRNA gene of mitochondrial DNA, a region not previously known to produce functional peptides. This makes it part of a newly discovered class of signaling molecules called mitochondrial-derived peptides (MDPs). Its 16 amino acid sequence (MRWQEMGYIFYPRKLR) is highly conserved across 14 species including humans and mice, suggesting it plays a fundamental biological role. Under resting conditions MOTS-c is localized to mitochondria, but under metabolic stress it translocates to the nucleus where it modulates gene expression. It was first described by Changhan Lee at the Pinchas Cohen laboratory at USC in a landmark 2015 Cell Metabolism paper.
Mechanism of Action
MOTS-c primarily acts as an AMPK (AMP-activated protein kinase) pathway activator, one of the master regulators of cellular energy homeostasis. AMPK activation promotes glucose uptake in skeletal muscle, fatty acid oxidation, and mitochondrial biogenesis while suppressing inflammatory pathways. MOTS-c also inhibits the MAP kinase and c-fos signaling pathways, contributing to its anti-inflammatory effects. Its nuclear translocation under stress conditions allows it to directly modulate adaptive gene expression, a retrograde signaling mechanism from mitochondria to nucleus that represents a novel form of cellular communication. Levels naturally rise with exercise and fall with aging, which has driven significant interest in exogenous supplementation as an aging intervention.
Use Cases
MOTS-c's most studied application is metabolic regulation, the 2015 discovery paper showed that MOTS-c treatment in mice reduced obesity, improved insulin sensitivity, and promoted metabolic homeostasis even on a high fat diet. Animal studies have consistently shown reductions in body weight, improved glucose metabolism, and protection against insulin resistance.
In the longevity space MOTS-c is studied for its age-related decline, circulating levels decrease significantly with age in both mice and humans, and exogenous administration in aged mice has shown improvements in physical performance and metabolic function. It is considered an exercise mimetic because it replicates aspects of the metabolic response to physical activity.
Cardiovascular research shows MOTS-c prevents cardiac dysfunction and pathological remodeling through AMPK pathway activation. A separate line of research has identified a role in plasma membrane repair, with implications for muscular dystrophy and ischemia-reperfusion injury.
All current evidence is from animal models and in vitro studies. No human clinical trials have been completed and human efficacy cannot be confirmed at this time.
Known Risks
Human safety data is absent given the lack of completed clinical trials. Animal studies have shown a favorable safety profile with no significant adverse effects reported. The AMPK activation mechanism is generally considered beneficial but long-term effects of exogenous MOTS-c supplementation in humans are unknown. As a naturally occurring endogenous peptide its tolerability is expected to be good but this has not been validated in human trials. Research compound only.
Available Forms
Available as a lyophilized sterile powder for reconstitution, typically supplied in vials of 5-10mg. Administered via subcutaneous injection in research contexts. No oral formulation, peptide structure makes oral bioavailability poor without specialized delivery systems. Research compound only.
Regulatory Status
No regulatory approval from any major health authority. Not available through licensed compounding pharmacies. Research compound only, supplied as lyophilized powder for laboratory use. Not approved or intended for human therapeutic use.
Sources
https://pubmed.ncbi.nlm.nih.gov/25738459/
https://pubmed.ncbi.nlm.nih.gov/31926126/
https://pubmed.ncbi.nlm.nih.gov/36670507/
https://pubmed.ncbi.nlm.nih.gov/31293078/
Similar Compounds
Carnosine, Sermorelin, CJC-1295, Humanin
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