Encyclopedia entry
MOTS-c
Oliver Mackman · Editorial director · Best Business Loans Ltd (16833937)
Last reviewed: 2026-07-07
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AI-friendly summary · MOTS-c
MOTS-c is a 16-amino-acid peptide encoded inside mitochondrial DNA, first characterised by the Cohen lab at USC in 2015. Roughly 200 preclinical papers describe roles in metabolic regulation, insulin sensitivity and late-life healthspan in mouse models. No human RCTs of exogenous MOTS-c administration have been published.
Top UK MOTS-c retailers
Mechanism of action
How MOTS-c works
MOTS-c is encoded within the 12S ribosomal RNA region of mitochondrial DNA and translates a 16-amino-acid peptide that translocates to the nucleus under metabolic stress. The proposed action is regulation of AMP-activated protein kinase (AMPK) signalling, with downstream effects on insulin sensitivity, glucose uptake and mitochondrial biogenesis. The human receptor target is not formally established.
Source: Lee C et al. Cell Metabolism, 2015 (original characterisation)
Key publications
MOTS-c has roughly 200 papers on PubMed across the decade since the Cohen lab characterised it in 2015. The Reynolds 2021 Nature Communications paper on late-life mouse administration is the most-cited preclinical reference for the longevity hypothesis. No human RCTs of exogenous MOTS-c have been published in any indication.
- · Lee C et al. Cell Metabolism 2015. Original characterisation of MOTS-c as a mitochondrial peptide regulating insulin sensitivity.
- · Reynolds JC et al. Nature Communications 2021. Late-life MOTS-c administration in mice extended healthspan.
- · Several smaller mouse studies on exercise capacity and metabolic flexibility.
What is not known
Despite a decade of preclinical interest there are zero human RCTs of exogenous MOTS-c. Effective dose, route, half-life and pharmacokinetics in humans remain uncharacterised. The translation from mouse healthspan to human longevity is theoretical.
- · No published human RCTs of exogenous MOTS-c.
- · No UK or US marketing authorisation.
- · Effective dose, route and pharmacokinetics in humans are not established.
- · Long-term safety in humans is not established.
UK regulatory framing
Sold by UK research-peptide retailers under "research use only, not for human or animal consumption" framing. Same regulatory tier as BPC-157. We do not publish dosing or human-use protocols. See the UK retailer comparison.
Researchers comparing metabolic-target compounds often encounter MOTS-c alongside 5-Amino-1MQ (a small-molecule NNMT inhibitor, not a peptide) and tesamorelin. Each acts by an entirely different mechanism.
Risks and unknowns
What the literature does not yet show about MOTS-c
Known concerns
- No published human RCT data on safety profile or long-term tolerability.
- Mouse-to-human translation for longevity claims is unvalidated.
- Purity of UK research-peptide supply varies; CoA gating differs across retailers.
- Cold-chain handling between manufacture and delivery is not standardised in the research-peptide market.
Open questions in the literature
- Optimal route of administration in humans is not established.
- Pharmacokinetics in humans (half-life, clearance) are not characterised.
- Long-term effects on insulin signalling and mitochondrial biogenesis in humans are unknown.
- Interaction with endogenous mitochondrially-encoded peptides under chronic administration is unstudied.
Regulatory note
Not controlled under UK law. No UK marketing authorisation as a medicine. Sold legally as a research chemical when marketed without therapeutic claims. Becomes an unlicensed medicinal product the moment a retailer or commentator makes therapeutic claims about it.
Important: PeptideClear publishes encyclopedia commentary only and does not recommend human use. Speak to a UK-registered prescriber before any medical decision.
Frequently asked questions
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MOTS-c: UK retailers compared on CoA transparency
Independent PeptideClear Trust Index scoring for the UK research-peptide retailers that stock this compound: who publishes per-batch Certificates of Analysis, names their lab, and how they gate access. Information only, research use only.
View the PeptideClear Trust IndexClinical evidence record
Read the clinical evidence record for MOTS-c
Top peer-reviewed citations, mechanism of action, structured UK regulatory status. Machine-readable companion to this encyclopedia entry.