D tier · weak
Humanin has an unusually deep, independently replicated mechanistic literature spanning twenty-five years and a defined set of receptors and binding partners, but no published interventional human trial of administered humanin exists.
humanin
Humanin is a 24-amino-acid peptide encoded by an open reading frame within the mitochondrial 16S rRNA gene MT-RNR2, identified in 2001 as a rescue factor that protected neurons from familial Alzheimer's disease insults. Its cytoprotective biology is well characterised in cells and rodents, but the published human literature appears to be descriptive rather than interventional.
// we supply this one
available as a research reagent
≥ 99% HPLC · lyophilised powder · batch certificate published. Grade D above is our own and is not adjusted because we stock it.
the explanation
Humanin is a tiny peptide that the mitochondria themselves encode, discovered because it kept brain cells alive under conditions that normally killed them. Two decades of laboratory and animal work back up that protective effect, but nobody has published a proper trial of giving it to people.
regulatory status
Not approved in any jurisdiction; research compound only
Humanin holds no marketing authorisation anywhere and is not a recognised medicine for any indication. It is an endogenous human peptide encoded in mitochondrial DNA rather than a synthetic invention, but no regulatory body has reviewed a synthetic humanin product. Searches of the indexed literature identified no published interventional trial of administered humanin in humans.
how it works · proposed mechanism
Humanin behaves as a stress-responsive cytoprotective signal acting both inside the cell and at cell-surface receptors.
Encoded inside mitochondrial rRNA
An open reading frame within the mitochondrial 16S rRNA gene MT-RNR2 encodes this 24-residue peptide, an unusual origin for a signalling molecule. That origin places it in the mitochondrial-derived peptide family alongside MOTS-c.
Blocks BAX-family apoptosis
Humanin binds the pro-apoptotic BCL-2 family proteins BAX, BID and BIM, and also interacts with IGFBP3 and amyloid-beta 42. This intracellular arm underlies the neuroprotection described in the original 2001 discovery work.
Surface receptors and JAK-STAT3
Secreted humanin engages a receptor complex that activates JAK-STAT3 signalling and acts as a ligand at formyl peptide receptors FPR2/FPRL1 and FPR3/FPRL2. Reported downstream effects include protection of retinal and endothelial cells from oxidative stress, promotion of mitochondrial biogenesis and reduced inflammatory responses.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Humanin's mechanistic literature is genuinely strong and independently replicated, which makes it easy to mistake for clinical evidence, yet the entire case rests on cell culture, rodents and molecular characterisation. Twenty-five years after its discovery there is still no published trial of administering humanin to a human being.
key published findings
- Cell culture: Hashimoto et al. (PNAS 2001;98(11):6336-6341) identified humanin as a rescue factor abolishing neuronal cell death caused by a wide spectrum of familial Alzheimer's disease genes and by amyloid-beta.
- Cell culture (follow-up): Hashimoto et al. (J Neurosci 2001;21(23):9235-9245) characterised neuroprotection by humanin in detail against a range of Alzheimer's-disease-relevant insults, extending the original single-insult finding.
- Molecular (human protein data): UniProtKB Q8IVG9 records humanin as a 24-residue MT-RNR2-encoded peptide (MAPRGFSCLLLLTSEIDLPVKRRA) that is secreted and also localises to cytoplasm, mitochondrion and nucleus, binds BAX, BID, BIM, IGFBP3 and amyloid-beta 42, and acts at FPR2/FPRL1 and FPR3/FPRL2, with 37 supporting references spanning 2001-2016.
- Review-level framing: reviews in Life Sciences (2021), Archives of Cardiovascular Diseases (2020) and Expert Opinion on Therapeutic Targets (2019) all describe humanin as a therapeutic target or candidate rather than an established therapy, indicating that no clinical evidence base had emerged by those dates.
- Literature audit: a PubMed search for humanin as a mitochondrial-derived peptide returns roughly 175 records spanning 2006-2026, dominated by preclinical and mechanistic work, with no interventional human administration study identified.
limitations of the evidence
- No interventional human data of any kind exist, and therefore no human pharmacokinetics, dose-response relationship or safety characterisation.
- A substantial share of the preclinical literature uses the S14G analogue (HNG) rather than native humanin, so reported effects are not always attributable to the marketed native sequence.
- Native humanin contains an internal leucine-rich hydrophobic stretch that complicates aqueous handling, and much of the published work uses modified analogues or non-physiological delivery.
documented safety signals
- No published human safety data; safety has never been assessed in an interventional study in any human population.
- Reviews position humanin as a target in cancer as well as in degenerative disease, and its core mechanism is the suppression of apoptosis - a theoretical concern for the survival of unwanted cells that has not been evaluated in humans in either direction.
identity
| full name | Humanin (MT-RNR2-encoded mitochondrial-derived peptide) |
| category | Growth Hormone |
| modality | peptide |
| formula | C119H204N34O32S2 |
| molar mass | 2687.3 g/mol |
| sequence | MAPRGFSCLLLLTSEIDLPVKRRA |
laboratory handling
| storage | Supplied as a lyophilised powder; research peptide is generally stored desiccated at -20 °C and protected from light. |
| solubility | Less water-soluble than shorter polar peptides because of the internal leucine-rich hydrophobic stretch; laboratory handling generally requires an organic co-solvent or dilute aqueous acid, and the single cysteine makes it sensitive to oxidation. |
| co-studied with | No published study evaluates humanin in combination with any other compound in this index. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedUniProt Knowledgebase · 2025 · official
Life Sciences 264:118679 · 2021 · review
Archives of Cardiovascular Diseases 113(8-9):564-571 · 2020 · review
Expert Opinion on Therapeutic Targets 23(2):117-126 · 2019 · review
Proceedings of the National Academy of Sciences USA 98(11):6336-6341 · 2001 · preclinical
Journal of Neuroscience 21(23):9235-9245 · 2001 · preclinical
others in Growth Hormone