Humanin

Short 24-amino-acid peptide encoded in mitochondrial DNA with reported cytoprotective and metabolic effects in preclinical research.

Overview

Humanin is a 24-amino-acid peptide encoded by a small open reading frame in the mitochondrial 16S ribosomal RNA gene (MTRNR2). It was first identified in a screen for factors protective against Alzheimer-related toxicity and has since been studied for cytoprotective, metabolic, and longevity-related effects across many cell and animal models. Together with related mitochondrial-derived peptides such as MOTS-c, it helped establish the concept that mitochondria release short bioactive peptides.

Mechanism

Humanin is secreted and acts through at least one cell-surface receptor complex (a heterodimer of the ciliary neurotrophic factor receptor and the cytokine receptor WSX-1) as well as through intracellular targets. Reported signaling includes activation of the STAT3 and Akt survival pathways, inhibition of apoptosis, reduction of oxidative stress, and preservation of mitochondrial function. Potent analogs such as HNG (with a glycine-for-serine substitution at position 14) are commonly used in research.

Dosing

Humanin and its analogs have been administered by injection in rodent studies at protocol-specific doses, and some analogs are designed for oral activity in animal work. No human research dosing has been established, and published human data are minimal.

Expected Effects

protection against amyloid-beta and other cytotoxic insults in cell and animal models
improved survival signaling and reduced apoptosis in stressed cells
beneficial effects on glucose metabolism and insulin sensitivity reported in rodent studies
preservation of cognitive function in some mouse models of Alzheimer-related pathology

Side Effects & Tolerability

Tolerability data come almost entirely from cell and rodent studies, which have not reported major toxicity for native humanin. Because it is an endogenous peptide, immunogenicity risk is considered low, but systematic human safety data are absent.

Storage

Lyophilized humanin should be stored desiccated, protected from light, and kept frozen at -20 deg C or below. Reconstituted solutions should be refrigerated at 2-8 deg C and used within a short window; avoid repeated freeze-thaw cycles.