Humanin is a 24-amino-acid peptide encoded within the mitochondrial genome rather than the nuclear genome. It belongs to the mitochondrial-derived peptides (MDPs), a small class that also includes MOTS-c and the small humanin-like peptides, and it is one of the few members of that class with a substantial mechanistic literature. This page sets out what that literature contains, and where it stops.
What humanin is
Humanin was identified in 2001 by functional expression screening of a cDNA library built from post-mortem occipital-lobe tissue, a brain region that is comparatively preserved in Alzheimer's disease. The screen sought factors that blocked neuronal cell death induced by familial Alzheimer's disease gene mutants and by amyloid-beta. The 24-mer that emerged rescued cells across several of those insults, which is why the early literature frames humanin as a neuroprotective or cytoprotective factor rather than as a hormone.
The peptide is encoded by an open reading frame within mitochondrial 16S ribosomal RNA, making it an MDP. Circulating humanin concentrations have been reported to decline with age in both mice and humans, a finding that framed the peptide as a candidate signal in the biology of ageing. That is a hypothesis, not a demonstrated mechanism.
The analogue HNG, or S14G-humanin
Structure-activity work in the early 2000s mapped which residues humanin needs for neuroprotection, identifying Cys8 and Ser14 as essential and the Pro3-to-Pro19 region as the active core. Substituting glycine for serine at position 14 yields S14G-humanin, also called HNG. In neuroprotection assays against Alzheimer's-relevant insults, HNG has been reported as roughly a thousand times more potent than the parent peptide. Most of the mechanistic and in vivo work since then has used HNG rather than native humanin.
What the mechanistic literature shows
The preclinical record is broad. Humanin and HNG have been reported to act against oxidative stress, ischaemia-reperfusion injury and apoptosis, and, in cell and rodent models, against amyloid-related neurotoxicity. In vitro work describes protection of endothelial cells from oxidised-LDL stress. Rodent work describes reduced infarct size and preserved cardiac function after ischaemia-reperfusion. HNG has been reported to improve motor coordination, spatial-memory search strategy and Y-maze alternation behaviour in aged or transgenic mouse models. Metabolic reviews place humanin alongside MOTS-c and SHLP2 in glucose regulation and insulin sensitivity, noting that circulating MDPs tend to be lower in obesity and diabetes.
Where the evidence stops
Almost all of this is in vitro or rodent work. The human record is observational: circulating concentrations and their association with disease states. No controlled human cognitive or metabolic trial of humanin or HNG has been completed, and the mouse studies rest on small group sizes.
Evidence grade: Anecdotal. A large and mechanistically interesting preclinical column, with no controlled human trial of the peptide itself. Class-level reviews and observational concentration studies are not substitutes for one.
The UK position
Neither humanin nor any of its analogues is a licensed medicine in the UK. They have no UK marketing authorisation from the MHRA; any supply is governed by the Medicines Act 1968 and the Human Medicines Regulations 2012. As with other mitochondrial-derived peptides, humanin is discussed here as a research compound only.
All compounds named on this page are described for research and reference purposes only. Nothing here is consumption, dosing or self-administration advice, and nothing here claims that any peptide treats, cures or prevents any condition.
This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.