MOTS-c
MOTS-c (Mitochondrial ORF)
MOTS-c is a 16-amino acid mitochondria-derived peptide encoded within the 12S rRNA gene of the mitochondrial genome, making it unique among known peptides. It is primarily studied for its roles in metabolic regulation, insulin sensitivity, exercise performance enhancement, and longevity, with emerging research suggesting anti-inflammatory and neuroprotective properties. It is used in research settings and by biohackers seeking metabolic optimization, weight management support, and healthy aging benefits.
Mechanism of Action
MOTS-c activates AMPK (AMP-activated protein kinase) signaling, which increases glucose uptake and fatty acid oxidation while inhibiting the folate cycle and de novo purine synthesis through accumulation of AICAR, a known AMPK activator. It translocates to the nucleus under metabolic stress conditions where it regulates adaptive nuclear gene expression, particularly genes involved in mitochondrial biogenesis and antioxidant defense. Additionally, MOTS-c modulates the gut microbiome and interacts with systemic metabolic pathways to improve insulin sensitivity and reduce obesity-related inflammation.
Evidence by Health Goal(17 goals)
Dosing Protocols
Morning, ideally 30-60 minutes before exercise or on an empty stomach
Cycle: 8-12 weeks on, 4 weeks off
Administered subcutaneously in the abdomen or thigh. Lower doses of 5mg are typical for beginners or those focused on metabolic health; higher doses up to 10mg are used in performance contexts. Reconstitute lyophilized powder with bacteriostatic water. Some protocols use daily dosing at lower amounts (2-5mg) for longevity-focused use.
Safety & Side Effects
MOTS-c has a relatively favorable short-term safety profile in rodent studies and limited human data, with no severe adverse events reported in early clinical observations; however, long-term safety in humans is not yet established due to limited clinical trials. It is not FDA-approved for human use and is sold strictly as a research compound in most jurisdictions, meaning quality control, purity, and dosing accuracy vary significantly between vendors.
Possible Side Effects
- !Injection site redness, swelling, or mild irritation
- !Transient fatigue or lethargy following initial doses
- !Mild nausea or gastrointestinal discomfort, particularly early in a cycle
- !Hypoglycemia risk in individuals with already low blood glucose or concurrent insulin use
- !Temporary increase in hunger or appetite changes
- !Headache or lightheadedness in early use
- !Flushing or warmth at or near injection site
Interactions
- -May potentiate hypoglycemic effects of insulin and oral antidiabetic medications such as metformin - monitor blood glucose closely
- -Additive AMPK activation when combined with metformin may cause excessive energy substrate depletion or lactic acidosis in susceptible individuals
- -May enhance effects of other mitochondria-targeting compounds such as MitoQ or SS-31, increasing risk of blood pressure reduction
- -Potential synergistic interaction with other longevity peptides (e.g., Humanin, BPC-157) - combined effects are largely unstudied
- -May alter response to exogenous hormones including growth hormone and testosterone due to downstream metabolic signaling overlap
Cost & Where to Buy
Price depends heavily on vendor purity (HPLC-verified vs. unverified), dose per vial, and vial quantity. A typical 5mg vial from a reputable research peptide supplier costs $40-80; a 3-5x weekly protocol at 5-10mg per dose requires 4-8 vials per month. Higher-purity pharmaceutical-grade sourcing significantly increases cost.
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