What is the half-life of MOTS-c?
The published plasma half-life of MOTS-c in preclinical models is short — in the hour range — but the compound’s tissue-level effects on AMPK signalling and downstream metabolic responses persist across days following each dose. Protocol dosing typically uses 2-3 times weekly subcutaneous administration rather than daily, anchored to the functional response time scale.
What the research literature says
MOTS-c is a small 16-amino-acid peptide without engineered long-acting modifications, so the plasma pharmacokinetics reflect the unmodified short circulating half-life typical of peptides of this size. The Lee characterisation work (PMID 25738459) and the follow-up muscle and fat metabolism work (PMID 27216708) established the dose-response framework that anchors typical research-protocol cadence.
The functional pharmacology operates on a longer time scale than the plasma half-life through AMPK-axis tissue-level signalling. The Yang exercise-synergy work documented sustained PGC-1α expression changes and insulin-sensitivity effects across multi-week protocols using 2-3 times weekly dosing (PMID 33722744). The Kim nuclear-translocation work characterised the metabolic-stress-responsive behaviour where MOTS-c translocates from cytosol to nucleus and regulates nuclear gene expression on a time scale that extends beyond plasma clearance (PMID 29983246).
The 2023 Jiang neuropathic-pain work used a similar multi-week dosing framework with AMPK-pathway involvement as the integrated mechanistic readout (PMID 37285113). Researchers running MOTS-c protocols typically anchor dosing-interval choice to the functional response time scale rather than the plasma-clearance time scale.
Why this matters in research context
The plasma-vs-tissue half-life distinction is pronounced for MOTS-c. Researchers running plasma-based pharmacokinetic assays see rapid clearance signals; researchers measuring tissue-level AMPK-axis or metabolic responses see effects accumulating across the multi-day window. Protocol design typically anchors dosing interval to the functional response time scale, which is why 2-3 times weekly dosing is common despite the short plasma half-life.
Related compounds
- MOTS-c 10mg — the compound covered by this answer
Related research questions
References
- Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015;21(3):443-454. [PMID 25738459]
- Kim KH et al. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab 2018;28(3):516-524. [PMID 29983246]
- Yang B et al. MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathway. Biochim Biophys Acta Mol Basis Dis 2021;1867(6):166126. [PMID 33722744]
Research-questions pages describe research-context use of peptide-research terminology. They do not constitute medical, veterinary, or clinical advice. MOTS-c is sold strictly as a research-grade reagent for laboratory and bench research applications.