MOTS-c

MOTS-c is unusual — it's a peptide encoded not in the cell's nucleus but within mitochondrial DNA. It behaves like a metabolic stress signal that helps coordinate how cells use energy.

When the body is under metabolic stress, MOTS-c activates AMPK (a master energy sensor) and antioxidant gene programs, and can move into the nucleus to influence gene expression — effects linked to better insulin sensitivity and glucose handling in lab and animal studies.

Most of the supporting data are preclinical, with human evidence still mostly observational. It's an area of genuine scientific interest, but its therapeutic value in people remains unproven.