Humanin

Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) encoded in the 16S ribosomal RNA region of mitochondrial DNA, discovered through its ability to protect neurons from amyloid-beta toxicity associated with Alzheimer's disease. Research demonstrates humanin possesses broad cytoprotective properties, protecting against cellular stress, oxidative damage, and apoptosis across multiple tissue types. The peptide acts through multiple mechanisms including binding to IGFBP-3, activating the STAT3 pathway, and modulating Bax-mediated apoptosis. Studies indicate humanin levels decline with age and may correlate with longevity in centenarians. Research shows protective effects in models of cardiovascular disease, diabetes, stroke, and age-related macular degeneration. Humanin improves insulin sensitivity and glucose homeostasis through peripheral and central mechanisms. Analogs with enhanced potency and stability (HNG, HNGF6A) have been developed for research applications. The peptide represents an important mediator of the retrograde signaling from mitochondria to the nucleus and other cellular compartments.

Evidence is overwhelmingly preclinical or observational. There are no human dosing, safety, or efficacy trials; the peptide is unstable in vivo, and analogs (e.g., HNG) are used in research. Anti-aging claims remain unproven.

Endogenous 24-amino-acid peptide encoded in mitochondrial 16S rRNA (MT-RNR2) and secreted from cells. Potency-enhanced analogs (e.g., S14G-humanin) were developed for stability; human pharmacokinetics of exogenous humanin are not established.