Humanin

Humanin (HN) is a small peptide encoded by a short open reading frame within the mitochondrial 16S rRNA gene (MT-RNR2). First described in 2001 during research into factors protecting neurons from amyloid-beta toxicity, it was the first member of the mitochondrial-derived peptide (MDP) family to be identified. Depending on where it is translated, the peptide exists as a 21-residue form (mitochondrial translation) or the 24-residue cytoplasmic form (MAPRGFSCLLLLTSEIDLPVKRRA) described here.

In preclinical models, humanin is reported to have cytoprotective and anti-apoptotic activity. Intracellularly it is described as binding pro-apoptotic proteins (BAX, tBID and BimEL) to suppress apoptosis, while extracellularly it is reported to signal through formyl peptide receptors (FPRL1/FPRL2) and a tripartite CNTFR/WSX-1/gp130 cytokine receptor complex, engaging downstream STAT3, ERK1/2 and AKT pathways. These mechanisms have been linked in cell and rodent studies to reduced oxidative and endoplasmic-reticulum stress. A rodent ortholog (rattin) and synthetic analogs such as the more potent S14G variant (HNG) are commonly used as research tools and are distinct entities from native humanin.

Humanin has also been studied as a circulating biomarker associated with aging, metabolic stress and insulin/IGF signaling, with some observational human data reported. However, the evidence base remains predominantly preclinical: there are no completed human efficacy trials, and pharmacokinetics, dosing and safety in humans are not characterized. Reported circulating humanin is short-lived in rodent studies (plasma half-life under roughly one hour in mice, in part via IGFBP3-dependent clearance), and no reliable human pharmacokinetic half-life has been established.

Humanin is not an approved medicine. It is not FDA-approved and holds no UK/MHRA marketing authorisation; it is supplied and handled only as a research chemical / reference material for laboratory use, not for administration to humans or animals. Nothing here should be read as a therapeutic claim or as guidance for human use.