Humanin

Humanin is a mitochondria-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of the mitochondrial genome. Discovered in 2001, it was the first MDP identified and has since become a cornerstone of mitochondrial biology research. Humanin exhibits potent cytoprotective properties, particularly in models of oxidative stress, apoptosis, and age-related cellular decline. Its mechanism of action involves interaction with IGFBP-3 (preventing its pro-apoptotic signaling), direct binding to BAX (blocking its translocation to mitochondria and subsequent cytochrome c release), and activation of the STAT3 signaling pathway. Research has demonstrated Humanin's neuroprotective effects against amyloid beta toxicity in Alzheimer's disease models, its cardioprotective properties against ischemia-reperfusion injury, and its metabolic benefits including improved insulin sensitivity and reduced hepatic triglyceride accumulation. Circulating Humanin levels have been found to decline with age in humans, making it a key biomarker and research target in geroscience. Studies have also identified its role in reducing endoplasmic reticulum stress and protecting vascular endothelial cells from atherosclerotic damage.