Humanin is a 24-amino-acid peptide encoded within the mitochondrial genome — specifically in the MT-RNR2 gene, the 16S ribosomal RNA region — and it was the first mitochondrial-derived peptide ever identified. It did not come from a database search. It was found in 2001 in a cDNA library made from the occipital cortex of an Alzheimer's brain, selected because that region's neurons had survived, and it was isolated by screening for factors that protected cells from amyloid-beta toxicity. That discovery route explains why the humanin literature is framed around cytoprotection rather than metabolism.
MyPeptide supplies Humanin as a lyophilized powder in 5 mg and 10 mg vials within the mitochondrial peptides range. Research use only; not for human or veterinary use.
What is Humanin?
Humanin is one of a small family of mitochondrial-derived peptides: short open reading frames located inside the ribosomal RNA genes of the 16.5-kilobase mitochondrial circle, whose products are detectable in tissue and plasma. Its sequence is Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala, with CAS number 330936-69-1, molecular formula C119H204N34O32S2 and molecular weight 2,687.27 g/mol.
Three residues in that sequence shape how the material behaves in a laboratory. The run of four consecutive leucines at positions 9 to 12 creates a strongly hydrophobic stretch that limits aqueous solubility and encourages aggregation. The cysteine at position 8 carries a free thiol, which can form intermolecular disulfides and produce dimers on standing. And the N-terminal methionine is oxidation-prone. None of this makes the peptide difficult to work with, but it does mean that handling matters more than for a typical short peptide.
Origin and structure
The identification, by Nishimoto's group in Tokyo, used a functional screen: transfect a cDNA library into cells challenged with a familial Alzheimer's disease gene product, then find the clones that survive. The surviving clone encoded humanin. Because the open reading frame sits in mitochondrial DNA, humanin can be translated on mitochondrial ribosomes with the mitochondrial genetic code, and a nuclear-encoded variant translated in the cytosol has also been described — the two differ at one position, and the literature is not always explicit about which one a given study used.
Sequence-modified analogues appear throughout the literature and are often what a paper actually studied. The best known is HNG, in which serine 14 is replaced by glycine; it has been reported to be orders of magnitude more potent than the parent sequence in protection assays. A rodent homologue, rattin, is longer than the human peptide. Reading humanin literature carefully means checking which molecule is in the methods section.
How Humanin is thought to work
Two mechanistic routes are reported, and unusually for a peptide of this size, they operate on opposite sides of the cell membrane.
The extracellular route runs through a receptor complex. Humanin has been reported to bind a trimeric receptor made of ciliary neurotrophic factor receptor, WSX-1 and gp130, signalling through the JAK/STAT3 pathway. Separate work has reported binding at formyl peptide receptor-like 1 (FPR2), a G-protein-coupled receptor also engaged by amyloid-beta — a plausible route for competitive interference at that receptor.
The intracellular route is protein–protein interaction. Humanin has been reported to bind Bax and to block its translocation from cytosol to mitochondrial outer membrane, the committing step in intrinsic apoptosis; similar interactions have been described with Bid and with IGF binding protein 3. This arm requires the peptide to be inside the cell, which its hydrophobic core plausibly permits.
Both routes converge on the same reported outcome — reduced apoptotic signalling under stress — which is why humanin is described in the literature as cytoprotective rather than as metabolic or trophic. Which arm dominates in any given model is unresolved, and stating a single definitive mechanism for humanin would overstate the published record.
What the research has examined
Neuronal survival and amyloid models
The founding literature, and still the largest, examines protection of cultured neurons against amyloid-beta toxicity and against familial Alzheimer's gene products, extending into rodent models of memory impairment where the peptide or HNG was administered centrally. This is cell and animal work.
Metabolic and insulin studies
Rodent work has examined glucose handling and insulin sensitivity, with reported effects on hypothalamic signalling and hepatic glucose output. Circulating humanin has also been reported to correlate with insulin sensitivity measures in human observational studies.
Ageing and longevity cohorts
Plasma humanin has been reported to decline with age in humans and in several animal species, and to be higher in some long-lived cohorts and in the offspring of centenarians. These are association data.
Cardiovascular and endothelial models
Studies in ischaemia–reperfusion, atherosclerosis and endothelial cell models have reported reduced apoptotic markers and preserved function, consistent with the cytoprotective framing.
What is not established
There are no controlled human trials of administered humanin and no approved product. Much of the strongest published data used HNG rather than the native sequence, which is a genuine caveat when interpreting results for the parent peptide. Background on the family is in humanin and the mitochondrial-derived peptide family, and the direct comparison in humanin vs MOTS-c.
Forms and sizes we supply
| Attribute | Specification |
|---|---|
| Product | Humanin |
| Form | Lyophilized powder, sealed glass vial |
| Available sizes | 5 mg, 10 mg |
| Purity | ≥99% by HPLC, lot-matched COA |
| CAS number | 330936-69-1 |
| Molecular formula | C119H204N34O32S2 |
| Molecular weight | 2,687.27 g/mol |
| Chain length | 24 amino acids |
| Gene of origin | MT-RNR2, the mitochondrial 16S rRNA region |
| Reported targets | CNTFR/WSX-1/gp130 complex, FPR2, Bax, IGFBP-3 |
| Intended use | Laboratory research only |
Reconstitution and storage in a lab context
Humanin is the least straightforward peptide on this shelf to get into solution, and the leucine run is the reason. Bacteriostatic or sterile water is the usual solvent, and the product may require gentle warming and standing time; some published protocols take the peptide up in a small volume of DMSO first and then dilute into aqueous buffer. Solvent is added down the vial wall, and the vial is swirled and left rather than shaken — agitating a hydrophobic peptide encourages exactly the aggregation being avoided. A solution that stays hazy has not fully dissolved and should not be assumed to be at nominal concentration.
The arithmetic is a laboratory calculation: a 10 mg vial made up with 2 mL of diluent gives 5 mg/mL, or 5,000 mcg/mL, so 0.1 mL — the 10-unit mark on a U-100 syringe — contains 500 mcg. At 2,687.27 g/mol, 1 mg is approximately 0.37 µmol. Method detail is in our reconstitution guide.
Lyophilized vials are held at −20 °C, sealed and protected from light and moisture. Reconstituted material is kept at 2–8 °C for the study window or aliquoted and frozen; the free cysteine thiol makes dimer formation on standing a real possibility, so freshly prepared solution is preferable to long-held stock. Broader practice is in how to store peptides.
Purity, COA and how to read it
The identity check is a mass spectrometry result matching 2,687.27 g/mol. Two satellite masses are worth looking for on this sequence specifically. A peak at +16 Da indicates oxidation at the N-terminal methionine. A peak at roughly twice the parent mass, minus 2 Da, indicates a disulfide-linked dimer formed through the cysteine at position 8 — a species that will behave differently in an assay and that a purity percentage alone will not flag if it co-elutes. On the HPLC trace, a hydrophobic 24-mer gives a broader peak than a small polar peptide, so peak shape should be judged against that expectation rather than against an ideal chromatogram. Our guide to reading a peptide certificate of analysis covers the remaining sections.
Regulatory status
Humanin has no marketing authorisation as a medicine anywhere, no reference-listed product and no approved labelling, and it is not a dietary supplement. It is supplied as a research-use-only chemical for laboratory investigation by qualified personnel — not a supplement, not a medicine, and not for human or veterinary administration.
Related peptides and further reading
The other mitochondrially encoded peptide in wide research use is MOTS-c, from the 12S rRNA region, whose reported mechanism is metabolic rather than cytoprotective. SS-31 (Elamipretide) is not mitochondrially encoded at all but an engineered tetrapeptide that concentrates at the inner membrane. Broader orientation is in our peptides for energy and mitochondria research overview.