MOTS-c

A 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene (MT-RNR1), discovered in 2015 by Changhan Lee and Pinchas Cohen at USC. MOTS-c is studied in preclinical models as an AMPK activator via inhibition of the folate cycle and accumulation of AICAR. It has been characterized in research literature as an 'exercise mimetic' based on observations that endogenous levels increase ~11.9-fold in skeletal muscle following exercise.

The only human data comes from CB4211, a discontinued MOTS-c analog that completed Phase 1a/1b (CohBar, Inc., now dissolved).

Discovered in 2015 (Lee et al., Cell Metabolism). Studied in preclinical models for AMPK activation via folate cycle inhibition and AICAR accumulation. Kim et al. (Cell Metabolism 2018) demonstrated stress-induced nuclear translocation where MOTS-c regulates antioxidant response elements. Reynolds et al. (Nature Communications 2021) reported ~11.9-fold increase in skeletal muscle MOTS-c following exercise.

The only human-tested analog, CB4211, completed Phase 1a/1b (n=88) showing safety and 25% ALT reduction in NAFLD subjects but no significant liver fat reduction vs placebo. CohBar dissolved and CB4211 development is discontinued. Community-discussed protocol: 5 mg subcutaneously every 5 days for 20 days (4 injections). All community dosing is anecdotal and unvalidated.