Humanin
Humanin is a 24-amino-acid mitochondrial-derived peptide first described in 2001 as a factor protecting neurons from death linked to Alzheimer's disease genes. It is studied in cell and animal models of neurodegeneration, metabolism and aging and is not approved for any use.
Most published evidence on Humanin comes from animal and cell studies. Findings in those models have not been established in people.
Overview
Humanin was identified in 2001 by a Japanese research group that screened a cDNA library from the brain of a person with Alzheimer's disease for sequences able to rescue cultured neurons from death caused by familial Alzheimer's disease genes and amyloid-beta. The rescuing sequence encoded a short peptide that the authors named humanin. Its open reading frame lies within the mitochondrial gene for 16S ribosomal RNA, MT-RNR2, which made humanin the first recognized member of what are now called mitochondrial-derived peptides.
Since its discovery, humanin has been studied in cultured neurons, other cell types and rodent models of neurodegeneration, ischemia, diabetes, cardiovascular injury and aging. Circulating humanin can be measured in human blood, and observational studies have related its levels to age and various conditions. However, there are no completed controlled trials of humanin given to people. Its biology remains an active area of research, and reported protective effects should be regarded as preclinical findings.
Compare: Humanin vs MOTS-c.
Structure
Humanin is a linear peptide of 24 residues with the sequence Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala (MAPRGFSCLLLLTSEIDLPVKRRA). It is notable for a hydrophobic run of four leucines and a basic C-terminal region. Whether humanin is translated in mitochondria or in the cytoplasm affects the predicted length, and nuclear-encoded humanin-like sequences also exist. A widely used research analogue, HNG, replaces serine 14 with glycine and was reported to be considerably more potent in cell assays. Research peptides are usually supplied as lyophilized TFA or acetate salts.
Mechanism
Humanin appears to act both inside cells and through cell-surface receptors. Intracellular partners reported in cell studies include the pro-apoptotic protein BAX, whose translocation to mitochondria humanin was shown to inhibit, and IGF-binding protein 3. Extracellularly, humanin has been reported to signal through formyl peptide receptor-like 1 (FPR2) and through a receptor complex involving CNTFR, WSX-1 and gp130, activating STAT3 and related pathways. How these routes contribute in intact organisms, and which predominate in different tissues, remains under investigation.
Research
Neuronal survival and Alzheimer's models
The founding work and much subsequent research examined humanin in cultured neurons exposed to familial Alzheimer's disease mutant genes, amyloid-beta and other toxic insults, reporting reduced cell death. Rodent studies have tested humanin or HNG in models of amyloid pathology and memory impairment, with reported improvements in behavioral and histological measures. These findings are preclinical; the relevance of humanin to Alzheimer's disease in people has not been established in clinical trials.
Metabolism and insulin sensitivity
Rodent studies have reported that humanin and its analogues affect insulin sensitivity, glucose handling and pancreatic beta-cell survival, with proposed actions involving hypothalamic signaling. Some work in animal models of type 1 and type 2 diabetes reported delayed onset or improved metabolic measures. These experiments are generally small and use synthetic analogues at research concentrations, so they indicate biological activity rather than therapeutic potential in people.
Aging and circulating levels
Observational studies have measured circulating humanin and reported that levels tend to decline with age in humans and rodents, and that some long-lived animal models and offspring of centenarians show relatively higher levels. Other studies relate humanin levels to cardiovascular and metabolic conditions. Such associations do not show cause and effect, and assay methods for endogenous humanin vary, which complicates comparison across studies.
Evidence quality
Humanin has a substantial and multi-laboratory preclinical literature, which distinguishes it from many research peptides. Nevertheless, there are no published randomized trials of humanin administration in people, and its pharmacology, stability in circulation and safety in humans are not characterized. Much of the in-vivo work uses the HNG analogue rather than native humanin, so findings should be attributed to the specific peptide tested.
Regulatory status
Humanin is not approved by the FDA or any major regulator for any use, and it is not on the Section 503A bulk drug substances list. It has not completed clinical development as a drug. For anti-doping purposes it is not among the substances specifically named in the facts used here; check the current WADA Prohibited List, which covers non-approved substances under class S0.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page, and report HPLC purity with the chromatogram. Because the S14G analogue HNG and other variants circulate, the COA should state exactly which sequence was made; a serine-to-glycine change shifts the mass by a small but detectable amount. The N-terminal methionine and cysteine 8 are prone to oxidation, and the free thiol can form disulfide-linked dimers, so oxidized and dimeric species should be looked for. The hydrophobic leucine stretch can promote aggregation. The counter-ion should be named.
Open Humanin in the sequence analyzer to see the expected [M+H]+ and multiply charged ions for an MS identity check.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized humanin sealed at -20 °C or colder, protected from light and moisture, and warm vials to room temperature before opening. Because it contains methionine and a free cysteine, minimize exposure to air and consider degassed buffers or inert-gas overlay for solutions. Its hydrophobic region can make dissolution and aggregation behavior sensitive to pH and concentration. Prepare solutions for lab use in sterile buffer, aliquot them, store at -20 °C or below, and avoid repeated freeze-thaw cycles.
Download the Humanin data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention Humanin in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
What is a mitochondrial-derived peptide?
Mitochondrial-derived peptides are short peptides encoded by small open reading frames within the mitochondrial genome. Humanin, encoded within the 16S ribosomal RNA gene, was the first described. MOTS-c, encoded within the 12S ribosomal RNA gene, is another. Both are studied as signaling molecules linking mitochondria to the rest of the cell and body.
What is the difference between humanin and HNG?
HNG is a synthetic analogue of humanin in which serine 14 is replaced by glycine. In cell assays it was reported to be far more potent than native humanin, so it is often used in animal experiments. Because their potency differs, results obtained with HNG should not be assumed to apply equally to native humanin.
Is humanin FDA approved?
No. Humanin is not approved by the FDA for any use and has not been tested in completed clinical trials as a drug. Its research record consists of cell and animal studies plus observational measurements of circulating levels in people.
Related compounds
- MOTS-c
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene, described in 2015 as a regulator of metabolic homeostasis. Research is mainly in cell and rodent models, with limited human data.
- SS-31 (elamipretide)
SS-31, known as elamipretide, is a synthetic mitochondria-targeted tetrapeptide that binds the inner-membrane lipid cardiolipin. It received FDA accelerated approval in September 2025 as Forzinity for Barth syndrome.
- Epitalon
Epitalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) developed by Vladimir Khavinson's group in St. Petersburg, based on a pineal gland extract. It is studied in aging and telomere research, with evidence coming mostly from that group.
- FOXO4-DRI
FOXO4-DRI is a synthetic D-retro-inverso peptide designed to disrupt the interaction between the transcription factor FOXO4 and p53 in senescent cells. It was described in a 2017 Cell paper as a senolytic in mice; human data are absent.
References
- Hashimoto Y, Niikura T, Tajima H, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001. Find on PubMed
- PubMed: all indexed literature on Humanin
- ClinicalTrials.gov: registered studies mentioning Humanin
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