A mitochondria-derived peptide with neuroprotective, cytoprotective, and longevity-associated properties.
Encoded in the 16S rRNA locus of mitochondrial DNA, Humanin is secreted as a circulating peptide. It acts on a tripartite receptor complex (gp130/IL-6ST/CNTFR) to activate JAK/STAT and PI3K/AKT survival pathways. It antagonises the pro-apoptotic protein BAX and directly neutralises amyloid-β toxicity.
Circulating Humanin levels decline with age, and lower levels correlate with increased risk of Alzheimer's disease and cardiovascular disease in epidemiological studies. Offspring of centenarians have significantly higher Humanin levels than age-matched controls.
Humanin was discovered through expression cloning from surviving neurons in Alzheimer's brain tissue — it was the gene that rescued cells from Alzheimer's toxins. This discovery established 'mitochondria-derived peptides' (MDPs) as a new class.