MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene, first described in 2015. Published research is mostly mouse and cell work, plus one early-phase human safety trial of a related analog.
In cell and mouse studies, MOTS-c inhibited the folate cycle and de novo purine synthesis, which was linked to AMPK activation [1]. Under metabolic stress it moved into the nucleus in an AMPK-dependent way and interacted with stress-responsive transcription factors including NRF2 [2]. A 2024 study identified the kinase CK2 as a direct binding target whose activity was required for effects measured in mouse muscle [4]. Whether these pathways operate the same way in humans has not been established.
| Study | Model | Reported result | Source |
|---|---|---|---|
| Original MOTS-c discovery study [1] | Mouse High-fat-diet and aging models in mice; cultured cells | Researchers reported folate-cycle inhibition and AMPK activation in cells and metabolic measurements in high-fat-diet mice. | Peer-reviewed Cell Metabolism 2015 |
| Nuclear translocation under metabolic stress [2] | Cell Cultured cells under glucose restriction and oxidative stress | MOTS-c entered the nucleus in an AMPK-dependent manner and altered expression of genes carrying antioxidant response elements, interacting with NRF2. | Peer-reviewed Cell Metabolism 2018 |
| Physical capacity across ages [3] | Mouse Young, middle-aged and old mice; treadmill testing; late-life intermittent administration; separate human exercise sampling | Researchers measured treadmill performance in young, middle-aged and old mice. Researchers also measured endogenous MOTS-c in human muscle and blood around exercise. | Peer-reviewed Nature Communications 2021 |
| CK2 as a direct target [4] | Mouse Cell-free binding assays; mouse muscle-atrophy and glucose-uptake models | MOTS-c bound and activated CK2 in muscle. Reduced muscle atrophy and higher muscle glucose uptake in mice were blunted when CK2 activity was suppressed. | Peer-reviewed iScience 2024 |
| Islet cell senescence [5] | Mouse Islets from aged mice; S961-treated mice; NOD mouse strain | Researchers measured islet senescence markers and glucose tolerance in MOTS-c-treated vs control mice. | Peer-reviewed Experimental & Molecular Medicine 2025 |
| CB4211 (MOTS-c analog) phase 1a/1b [6] | Human Phase 1a: 65 healthy adults; phase 1b: 20 adults. Randomized, double-blind, placebo-controlled, up to 4 weeks | Primary endpoint: safety and tolerability. Analog, not native MOTS-c. Topline reported by developer press release; no peer-reviewed publication located. | Company-reported ClinicalTrials.gov / CohBar 2021 |
Human trials are listed for research context only; outcomes are reported in the linked publications. Animal and lab results do not establish effects in humans.
PureLab supplies MOTS-c for laboratory research. Lot-specific certificates of analysis are posted on the product page as they are issued.
View research-grade MOTS-c