LONGEVITY · Injectable
MOTS-c.
Mitochondria-derived metabolic regulator
How it works
Class & mechanism.
Class
Mitochondrial-Derived Peptide (MDP)
Mechanism
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino acid peptide encoded by a short open reading frame within mitochondrial 12S rRNA — the second known peptide encoded entirely within mitochondrial DNA. Under metabolic stress or exercise, MOTS-c translocates from the cytoplasm into the nucleus, where it acts as a retrograde mitochondrial-to-nuclear signal and directly regulates gene expression of stress-adaptation pathways containing antioxidant response elements (ARE). Its primary metabolic mechanism operates via the Folate-AICAR-AMPK axis: MOTS-c inhibits de novo purine biosynthesis and the folate cycle, causing AICAR accumulation which phosphorylates and activates AMPK — the master metabolic switch that drives glucose uptake, fatty acid oxidation, mitochondrial biogenesis via PGC-1α, and SIRT1-mediated anti-inflammatory signaling.
Did you know
MOTS-c is banned in competitive sports by WADA — which means regulators already consider it performance-enhancing enough to prohibit. It's essentially a molecular signal your mitochondria normally send during intense exercise, now available as an injection.
Benefits
What it does.
Exercise-mimetic metabolic activation — MOTS-c levels spike 11.9-fold in skeletal muscle and 1.6-fold in plasma following acute exercise in healthy young men, with AMPK activation mimicking key biochemical adaptations of physical training
Insulin sensitivity and metabolic flexibility — improves glucose uptake independent of insulin, reduces markers of insulin resistance, and corrects metabolic dysfunction in type 2 diabetes and PCOS models via AMPK/PGC-1α axis
Muscle and bone preservation — skeletal muscle MOTS-c rejuvenates aging-related muscle phenotypes in mice; MOTS-c activates AMPK in osteoblasts to prevent ovariectomy-induced bone loss and supports bone metabolism
Anti-inflammatory and cardiovascular protection — activates Keap1/Nrf2 antioxidant pathway, reduces pro-inflammatory cytokines, restores cardiac mitochondrial respiration in diabetic heart models, and suppresses NF-kB-mediated inflammaging
The science
Peer-reviewed findings.
Research supporting this compound's mechanisms and safety profile.
MOTS-c serum concentration positively correlates with lower-body muscle strength parameters in young adults, and circulating MOTS-c levels are significantly reduced in type 2 diabetes, gestational diabetes, PCOS, obese children, and coronary endothelial dysfunction — establishing it as a metabolic health biomarker
SOURCE · Domin R et al., International Journal of Molecular Sciences 24(19):14951, 2023; Ramanjaneya et al., 2019; multiple studies reviewed in Kong BS et al., Diabetes & Metabolism Journal 47(3):315–324, 2023
In ovariectomized female mice (menopause model), MOTS-c 5 mg/kg i.p. for 5 weeks significantly reduced white adipose and liver fat accumulation, activated brown adipose tissue, and improved insulin sensitivity via AMPK activation — suggesting particular relevance for post-menopausal metabolic decline
SOURCE · Lu H et al., Journal of Molecular Medicine 97:473–85, 2019; reviewed in Alzheimer's Drug Discovery Foundation MOTS-c monograph, 2025
MOTS-c restores mitochondrial respiration and citrate synthase activity in the type 2 diabetic heart through AMPK-mediated mitochondrial biogenesis, partially replicating the cardiac benefits of exercise in a rat T2DM model
SOURCE · Frontiers in Physiology 2025, doi:10.3389/fphys.2025.1602271; Nature Scientific Reports 2023
MOTS-c prevents pancreatic islet cell senescence and delays onset of diabetes in an experimental model, with MOTS-c-treated islet cells showing reduced senescence markers and preserved beta-cell function
SOURCE · Kong BS et al., Experimental & Molecular Medicine 57(8):1861–1877, 2025
Protocol
How to use it.
Dosing
Preclinical longevity/metabolic protocols: 5–15 mg/kg subcutaneous or intraperitoneal injection in mice. Human off-label protocols: 5–10 mg subcutaneous injection 1–3 times per week. MOTS-c does not cross the blood-brain barrier systemically — intranasal or intracerebroventricular administration required for direct CNS effects. USADA has added MOTS-c to its prohibited list for competitive sports.
Cycle
No formally established human cycling protocol. Research-based off-label cycles typically run 4–8 weeks on, 2–4 weeks off. Because MOTS-c is naturally induced by exercise and stress, some practitioners use it in focused metabolic or weight-loss phases rather than year-round.
Contraindications
When to skip it.
Banned by the World Anti-Doping Agency (WADA) and US Anti-Doping Agency (USADA) — prohibited in competitive sports. Sex-dependent effects noted: males show greater disruption of MOTS-c signaling in metabolic disease; pre-menopausal females may have partial estrogen-mediated protection. Not BBB-penetrant via standard SC injection — systemic injection will not produce direct cognitive effects. No human clinical trial safety data available.
Always cleared with your concierge before protocol start.
Pricing
What it costs.
Indicative range for MOTS-c, sourced from vetted US and EU dispensing suppliers. Concierge confirms the exact figure once your match is locked.
Indicative range (USD)
Sourced through vetted dispensing partners in the United States and European Union. Concierge confirms the exact figure once your match is locked.
- 0199% purity verified, third-party tested
- 02Includes vial and reconstitution guidance
- 03Concierge supplier match included with every protocol
See MOTS-c pricing — and your supplier match.
Pricing is unlocked once we know who you are. Take the 3-minute quiz and we'll match you to a US or EU dispensary based on your location and protocol fit.
- Live USD price range
- US & EU supplier shortlist
- Concierge sign-off on dosing
Indicative price range: $120–$180 USD