A 24-amino-acid mitochondrial-derived peptide encoded by the 16S rRNA mitochondrial gene — first described in 2001 by the Hashimoto / Nishimoto group at Keio from a cDNA library of an Alzheimer brain region that was unusually spared from disease.
Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) — sequence MAPRGFSCLLLLTSEIDLPVKRRA — encoded within the 16S rRNA region of the mitochondrial genome. It was the first member of the MDP family identified.
The discovery paper is Hashimoto et al. PNAS 2001 (PMID 11371646), "A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta." It came out of a functional cDNA-library screen for clones that protected neuronal cells from familial-AD-gene-induced and Aβ-induced death; the source library was the occipital lobe of an AD patient — a region relatively spared from the disease. (Some references date humanin's discovery to 2003. That's the year the IGFBP-3 binding partner was identified, Ikonen 2003 PMID 14561895. The peptide itself was first described in 2001.)
The discovery lab was Ikuo Nishimoto's group at Keio University in Tokyo. Nishimoto died in 2003; subsequent Japanese work continued under Yuichi Hashimoto and Masaaki Matsuoka. The major Western lab is Pinchas Cohen (now at USC Leonard Davis School of Gerontology), who later led the discovery of MOTS-c in 2015 and the broader MDP family (SHLPs and others). Humanin is the founding member of that family — MOTS-c, SHLP1–6, and other MDPs were discovered later on humanin's discovery template.
Humanin acts through multiple intersecting cellular survival pathways. The mechanism story is unusually well-mapped for a research peptide because two decades of work have come from both the Japanese discovery group and the Cohen lab.
The most-cited mechanism is anti-apoptotic action via Bax inhibition. Humanin binds Bax (a pro-apoptotic Bcl-2-family protein) and prevents its translocation from cytosol to mitochondria, blocking the mitochondrial apoptosis pathway. Source: Guo et al. Nature 2003 (PMID 12732850).
A second mechanism is IGFBP-3 partnership. Humanin binds insulin-like growth factor binding protein-3 (IGFBP-3) and modulates IGFBP-3-dependent cell survival. This was the bridge to Cohen-lab humanin work (Ikonen 2003, PMID 14561895). Third, humanin activates a heterotrimeric cytokine-receptor complex composed of CNTFR, WSX-1, and gp130, driving intracellular STAT3 phosphorylation (Hashimoto 2009, PMID 19386761). Fourth, hypothalamic / intracerebroventricular humanin in rodents improves peripheral insulin sensitivity and glucose homeostasis (Muzumdar 2009, PMID 19623253).
One claim worth ignoring: the "TRIM5α inhibition" mechanism that shows up in some encyclopedia entries and vendor copy has zero PubMed support. Skip it.
Most preclinical humanin literature uses analogs, not the wild-type peptide. Vendor copy that says "humanin protects against X in mouse models" is technically correct but leans on analog data more than wild-type data.
| Analog | Modification | Notes |
|---|---|---|
| HNG (S14G-Humanin) | Ser → Gly at position 14 | Most-studied. ~1000-fold more potent than wild-type in some neuroprotection assays. Workhorse of Alzheimer's mouse studies (Tajima 2005 PMID 15678515; Zhang 2012 PMID 21993310). |
| HNGF6A | S14G + F6A | Cohen-lab work; further-stabilized analog with improved metabolic activity. |
| Colivelin (AGA-(C8R)-HNG17) | Hybrid of HNG and ADNF | Enhanced potency and stability (PMID 26964005). |
| P3S (longevity variant) | Pro³ → Ser³ | Enriched in centenarians, especially APOE4 carriers (PMID 38520065). |
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Start Tracking FreeNo PubMed-indexed clinical trial of humanin in humans exists. All human evidence is observational biomarker work.
| Domain | Evidence | PMIDs |
|---|---|---|
| Neuroprotection (Alzheimer's) | Wild-type humanin rescues neuronal cells in vitro | 11371646, 11717357, 11327724 |
| HNG cognition (mouse) | S14G improves memory in Aβ-injection and APPswe/PS1dE9 models | 15678515, 21993310 |
| Anti-apoptosis / Bax | Bax binding blocks mitochondrial translocation | 12732850 |
| IGFBP-3 partnership | Regulates cell survival | 14561895 |
| Cytokine-receptor signaling | CNTFR/WSX-1/gp130 → STAT3 | 19386761 |
| Insulin action (rodent) | ICV humanin improves peripheral insulin sensitivity | 19623253 |
| Cardio-protection (rodent) | Reduces myocardial IR injury | 27434747, 34896254 (review) |
| Coronary endothelial function (human observational) | Higher circulating humanin = preserved function (n=102) | 23220334 |
| Cognitive aging | Mouse intervention + human observational | 30242290 |
| Aging-related MDP decline | Endogenous humanin and SHLPs drop with age | 27070352 |
| Retinal protection (in vitro) | RPE protection from oxidant injury | 32768357 |
| T2DM / AD biomarker | Plasma humanin differs by disease state | 33131010 |
| P3S longevity variant | Enriched in APOE4-carrying centenarians | 38520065 |
No human-trial-derived dose exists. Same caveat as MOTS-c — anything specific in vendor or forum copy is community practice, not clinically validated.
| Parameter | Common Range |
|---|---|
| Dose per injection | 500–1000 µg SC |
| Frequency | Daily, EOD, or twice weekly |
| Cycle length | 4–8 weeks on / similar off |
| Route | SC standard; intranasal occasionally reported |
Wild-type humanin has a minutes-scale half-life in rodents. Stabilized analogs (HNG, HNGF6A, colivelin) have longer half-lives — the design intent of those analogs is partly to overcome wild-type humanin's rapid clearance.
Pre-filled with a typical Humanin setup. Edit any field — the draw updates live.
Insulin syringe — 100 units = 1 mL
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For a 5 mg vial in 2 mL bacteriostatic water: 2.5 mg/mL, so 1 unit on a U-100 syringe = 25 µg. A 500 µg dose is 20 units; a 1000 µg dose is 40 units.
Lyophilized vials are stable at room temperature short-term; refrigerate for longer. Reconstituted vials should be refrigerated and used within 28 days. For the full protocol, see the Bacteriostatic Water guide.
No published human safety data on humanin or any analog. No FAERS, EudraVigilance, or Yellow Card entries.
Mechanism-derived concerns: humanin binds IGFBP-3, so chronic dosing could plausibly alter IGF-1 bioavailability. Anti-apoptotic mechanisms (Bax inhibition) and pro-survival signaling (STAT3) are pharmacologically attractive for neuroprotection but mechanistically aligned with tumor survival — active or prior cancer is a class contraindication. Humanin is endogenous, so theoretical immunogenicity is low; no published immunogenicity data.
Community user reports describe injection-site mild irritation as the most common acute issue. None of that is anchored in a peer-reviewed safety paper.
MOTS-c — sister mitochondrial-derived peptide. Different sequence, different gene origin (12S rRNA vs 16S), different mechanism (AMPK activation vs Bax/IGFBP-3/STAT3). Both Cohen-lab MDP family but mechanistically distinct.
SHLP1–6 — small humanin-like peptides; further Cohen-lab MDPs. Less studied; not commonly available as research chemicals.
Cerebrolysin — porcine brain extract, multi-component. Different family entirely.
HNG vs wild-type humanin — if the goal is the published preclinical effect, HNG (S14G) is the molecule the strongest mouse studies actually used.
Humanin is a research peptide not approved by the FDA for human use. It is sold only as a research chemical, and StackTrax does not endorse or facilitate personal use.
Quality varies enormously among research-chemical suppliers. At minimum, look for:
StackTrax’s preferred partner NextGen Peptides does not currently carry Humaninin their catalog, which is why you don’t see a direct purchase link here. Other major research-chemical suppliers carry it; we don’t specifically recommend one for this compound.
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Start Tracking FreeNo. Humanin is not approved by the FDA or EMA. There is no NDA on file and no IND. It is sold as a research chemical only. Humanin is not explicitly named on the WADA 2026 list, but is likely covered by the S2 catch-all (peptide hormones, growth factors, related substances and mimetics) since humanin signals via cytokine-receptor complexes.
Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded within the 16S rRNA region of the mitochondrial genome, rather than the nuclear genome. It was the founding member of the MDP family identified in 2001. Sister MDPs include MOTS-c (12S rRNA, AMPK activation) and SHLP1-6 (small humanin-like peptides). The Cohen lab at USC discovered MOTS-c and SHLPs later, building on humanin's discovery template.
Humanin was first described in Hashimoto et al. PNAS 2001 (PMID 11371646) by Ikuo Nishimoto's group at Keio University in Tokyo. It came out of a functional cDNA-library screen for clones that protected neuronal cells from familial Alzheimer's-gene and amyloid-beta-induced death. The source library was the occipital lobe of an AD patient, a region relatively spared from the disease. Some references date the discovery to 2003, but that is when the IGFBP-3 binding partner was identified (Ikonen 2003), not the peptide itself.
No PubMed-indexed clinical trial of humanin in humans exists. All human evidence is observational biomarker work, including a coronary endothelial function study (n=102, PMID 23220334) where higher circulating humanin correlated with preserved function, plasma humanin differences by T2DM/AD disease state (PMID 33131010), and the P3S longevity variant enriched in APOE4-carrying centenarians (PMID 38520065). Mechanistic and efficacy data is all in vitro or in rodents.
Humanin acts through multiple intersecting pathways. The most-cited is anti-apoptotic action via Bax inhibition (Guo 2003, PMID 12732850), where humanin binds Bax and prevents its translocation to mitochondria. It also binds IGFBP-3 to modulate IGFBP-3-dependent cell survival, activates a heterotrimeric cytokine-receptor complex (CNTFR/WSX-1/gp130) driving STAT3 phosphorylation, and in rodents improves peripheral insulin sensitivity. The TRIM5-alpha mechanism that shows up in some vendor copy has zero PubMed support.
HNG (S14G-Humanin) is a humanin analog with a Ser-to-Gly substitution at position 14. It is roughly 1000-fold more potent than wild-type humanin in some neuroprotection assays and is the workhorse of Alzheimer's mouse studies (Tajima 2005, Zhang 2012). Most preclinical humanin literature uses analogs like HNG, HNGF6A, or colivelin rather than wild-type, partly because wild-type humanin has a minutes-scale half-life in rodents. Vendor copy that says "humanin protects against X in mouse models" is technically correct but leans on analog data more than wild-type data.
No human-trial-derived dose exists. Community practice ranges are 500 to 1000 mcg SC per injection, dosed daily, every other day, or twice weekly, in 4 to 8 week cycles with similar off time. SC is standard; intranasal is occasionally reported. For a 5 mg vial in 2 mL bacteriostatic water, the concentration is 2.5 mg/mL, so 1 unit on a U-100 syringe equals 25 mcg (500 mcg = 20 units; 1000 mcg = 40 units).
No published human safety data on humanin or any analog exists. No FAERS, EudraVigilance, or Yellow Card entries. Community user reports describe injection-site mild irritation as the most common acute issue. Mechanism-derived concerns: chronic IGFBP-3 binding could alter IGF-1 bioavailability, and anti-apoptotic plus STAT3 signaling is mechanistically aligned with tumor survival, making active or prior cancer a class contraindication. Avoid in pregnancy or breastfeeding (no data) and use caution stacking with HGH, IGF-1 LR3, or IGF-1 DES given the IGFBP-3 axis overlap.
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StackTrax guides cover peptides and compounds that are not FDA-approved for the uses discussed. The dosing, reconstitution, and safety information is compiled from published research and community protocols for educational purposes only.
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