MOTS-c

Translocates from mitochondria to nucleus under metabolic stress, activates AMPK pathway, regulates folate cycle and de novo purine biosynthesis, improves insulin sensitivity. Exercise-inducible endogenous peptide.

Preclinical only. No approved use. Compounding use emerging in longevity medicine without clinical trial support.

No established contraindications due to lack of clinical data.

Cell Metabolism 2015 discovery paper. Mouse studies: lifespan extension, metabolic improvement. Only analog (CB4211) reached Phase I. No human therapeutic trials completed.

• 1.Lee C et al., Cell Metabolism 2015 — first identification of MOTS-c as mitochondrial-encoded signaling peptide. Prevented insulin resistance and obesity in mice. Discovery/Preclinical
• 2.Kim et al., Nature Commun 2018 — mitochondria-to-nucleus stress signaling mechanism
• 3.Reynolds et al., Nature Aging 2021 — exercise response in older adults and MOTS-c levels

NOT clinically tested in humans as therapeutic peptide. Only analog (CB4211) reached Phase I. Low bioavailability, poor stability, short half-life.