Humanin

Humanin arises from a short open reading frame within the 16S rRNA region of the mitochondrial genome (MT-RNR2) — it is therefore not encoded by nuclear DNA. Mechanistically, preclinical work describes a cytoprotective, anti-apoptotic effect via multiple pathways: an extracellular interaction with a trimeric receptor complex of gp130, CNTFR and WSX-1 with downstream activation of JAK2/STAT3 signalling, as well as intracellular interactions including inhibition of the pro-apoptotic protein BAX (and of tBID), binding to IGFBP-3 with modulation of the IGF-1 axis, and interaction with FPRL1/FPRL2 receptors. These models derive predominantly from cell culture and rodents; the extent to which they reflect human physiology after administration of exogenous synthetic humanin is not established by controlled human trials.