MOTS-c
16-amino-acid mitochondrial-derived peptide investigated in metabolic stress, exercise signalling and ageing biology.
Mechanism & research rationale
MOTS-c is encoded within mitochondrial DNA and has been linked to cellular stress responses, AMPK-associated metabolic signalling and mitochondria-to-nucleus communication. It is often discussed as a mitokine or mitochondrial-derived signalling peptide.
Human evidence
Human studies show that endogenous MOTS-c can change with exercise. A 2021 Nature Communications study measured increases in skeletal-muscle and circulating MOTS-c after exercise in healthy volunteers. This demonstrates physiological association, not that exogenous MOTS-c treatment reproduces exercise benefits in people. A 2026 systematic review of mitochondrial-derived peptides and exercise described the human evidence base as small and heterogeneous.
Preclinical / translational evidence
Mouse studies report effects on physical capacity, metabolic adaptation, insulin sensitivity and stress responses. These findings underpin current research interest but are not equivalent to proven outcomes in humans.
Key limitations
- Endogenous exercise-induced MOTS-c is not the same evidence question as administering synthetic MOTS-c.
- Controlled human intervention trials remain sparse.
- Assay methods and measured circulating concentrations vary across studies.