Humanin
Also known as: HN, HNG (S14G-Humanin), Humanin G, [Gly14]-Humanin
Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 16S rRNA gene. It is the founding member of the mitochondrial-derived peptide family and has demonstrated potent cytoprotective effects against Alzheimer's disease pathology, apoptosis, oxidative stress, and metabolic dysfunction.
Humanin is a 2,687.14 Da research peptide. Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 16S rRNA gene. It is the founding member of the mitochondrial-derived peptide family and has demonstrated potent cytoprotective effects against Alzheimer's disease pathology, apoptosis, oxidative stress, and metabolic dysfunction.
Also called: HN, HNG (S14G-Humanin), Humanin G
2,687.14
Molecular Weight
Daltons
2
Strong Evidence
benefits
5
Studies Cited
peer-reviewed
0-0
Typical Dose
2-10 mg/kg IP or SC (animal)
Overview
Humanin was discovered in 2001 by Nishimoto and colleagues through a functional screen for genes that protect neurons against Alzheimer's disease (AD)-related toxicity. it was found to be encoded not in nuclear DNA but within the mitochondrial genome; specifically within the 16S ribosomal RNA gene (MT-RNR2). This discovery established an entirely new concept: that mitochondria produce bioactive peptides (mitochondrial-derived peptides, MDPs) that function as retrograde signaling molecules communicating mitochondrial status to the cell and organism. Humanin is the founding and most studied member of this MDP family (which now includes MOTS-c, SHLP1-6). Endogenous humanin levels decline with age and are reduced in patients with Alzheimer's disease. The peptide has demonstrated notable cytoprotective activity: it protects neurons against amyloid-beta toxicity, prevents apoptosis triggered by multiple insults, improves insulin sensitivity, reduces inflammation, and protects against ischemic injury. The synthetic analog HNG ([Gly14]-Humanin, or S14G-Humanin) is 1,000x more potent than native humanin and is the form most commonly used in research. Humanin has been described as a mitochondrial stress signal that activates cellular survival programs.
Key Takeaways: Humanin
- Strongest evidence supports Humanin for alzheimer's disease neuroprotection and anti-apoptotic (cell survival)
- Research doses typically range from 0 to 0 2-10 mg/kg IP or SC (animal) via intraperitoneal or subcutaneous (animal models)
- 2 benefits with strong evidence, 3 moderate, 0 preliminary
- Half-life: ~30 minutes (estimated; limited pharmacokinetic data in humans)
- 5 cited research studies in this guide
Mechanism of Action
Humanin acts through multiple receptor systems: (1) FPRL1/FPR2 (formyl peptide receptor-like 1), the same receptor used by LL-37, activating ERK1/2 and STAT3 pro-survival signaling; (2) a trimeric receptor complex of CNTFR/WSX-1/gp130 (ciliary neurotrophic factor receptor complex), activating JAK2/STAT3 anti-apoptotic cascades; (3) direct binding to IGFBP-3, displacing it from IGF-1 and releasing free IGF-1 for receptor activation (insulin-sensitizing effect); (4) direct binding to BAX, the pro-apoptotic BCL-2 family member, preventing BAX translocation to mitochondria and blocking the intrinsic apoptotic cascade. Through STAT3 activation, humanin upregulates anti-apoptotic proteins (Bcl-2, Mcl-1, survivin) and reduces pro-apoptotic signaling. In Alzheimer's models, humanin directly antagonizes amyloid-beta-induced neurotoxicity by blocking Aβ-triggered BAX activation and preventing mitochondrial membrane permeabilization. It also reduces tau hyperphosphorylation through AKT/GSK-3β pathway modulation. Metabolically, humanin improves insulin sensitivity through IGFBP-3 sequestration and direct hypothalamic action on STAT3-mediated appetite regulation. As a retrograde mitochondrial signal, humanin levels reflect mitochondrial health — declining levels with aging may represent loss of a critical survival signal.
Research Benefits
Humanin at a Glance
Humanin acts through multiple receptor systems: (1) FPRL1/FPR2 (formyl peptide receptor-like 1), the same receptor used by LL-37, activating ERK1/2 and STAT3 pro-survival signaling; (2) a trimeric receptor complex of CNTFR/WSX-1/gp130 (ciliary neurotrophic factor receptor complex), activating JAK2/STAT3 anti-apoptotic cascades; (3) direct binding to IGFBP-3, displacing it from IGF-1 and releasing free IGF-1 for receptor activation (insulin-sensitizing effect); (4) direct binding to BAX, the pro-apoptotic BCL-2 family member, preventing BAX translocation to mitochondria and blocking the intrinsic apoptotic cascade.
Alzheimer's Disease Neuroprotection
Strong EvidencePotently protects neurons against amyloid-beta toxicity in cell and animal models. Reduces tau phosphorylation and prevents AD-related synaptic loss. HNG analog is 1,000x more potent.
Anti-Apoptotic (Cell Survival)
Strong EvidenceBlocks intrinsic apoptosis by directly binding BAX and activating STAT3/Bcl-2 anti-apoptotic cascades. Protects against multiple cell death triggers including oxidative stress, serum deprivation, and excitotoxicity.
Insulin Sensitization and Metabolic Improvement
Moderate EvidenceImproves insulin sensitivity by displacing IGFBP-3 from IGF-1 and through central hypothalamic action. Reduces visceral fat and improves glucose tolerance in animal models.
Ischemic Protection (Heart and Brain)
Moderate EvidenceProtects against ischemia-reperfusion injury in cardiac and cerebral models by preventing mitochondrial permeability transition and reducing apoptosis.
Age-Related Decline Biomarker and Intervention
Moderate EvidenceEndogenous humanin declines with age. Supplementation restores cytoprotective signaling, positioning humanin as both a biomarker of mitochondrial aging and a potential intervention.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| HNG (potent analog), animal research | 0–0 2-10 mg/kg IP or SC (animal) | Intraperitoneal or subcutaneous (animal models) |
| Intranasal research | 100–500 mcg | Intranasal (exploratory) |
Frequency
Once daily in animal research models
Timing
No established human dosing protocols
Cycle Length
Variable; 2-8 weeks in animal studies
Research Notes
- 1HNG ([Gly14]-Humanin) is 1,000x more potent than native humanin — the preferred research form.
- 2No established human dosing protocols; preclinical/early translational stage.
- 3Intranasal delivery is being explored for CNS applications.
- 4Endogenous humanin can be measured in plasma as a biomarker.
- 5MOTS-c (a related MDP) has entered human clinical trials, paving the way for humanin.
- 6Very early in clinical translation, primarily preclinical research.
Reconstitution Guide
Standard Reconstitution
Vial Size
5 mg
Bacteriostatic Water
1 mL
Concentration
50 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
Humanin vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 1 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at Frozen (-20°C) or refrigerated (2-8°C) after reconstitution. Use promptly; store reconstituted solution frozen for longer storage.
Storage Temperature
Frozen (-20°C) or refrigerated (2-8°C) after reconstitution
Shelf Life
Use promptly; store reconstituted solution frozen for longer storage
Important Notes
- •Reconstitute with sterile water.
- •HNG analog preferred for research — higher potency and stability.
- •24-amino acid peptide, moderate stability.
- •Store lyophilized powder at -20°C.
Humanin Dosing Calculator
Calculate daily intake, cycle totals, and vials needed with pre-filled protocols →
Humanin Reconstitution Calculator
Calculate concentration, syringe units, and doses per vial with auto-filled values →
Safety & Side Effects
Reported Side Effects
- !Limited human safety data; primarily studied in animal models
- !No significant toxicity observed in preclinical studies at therapeutic doses
- !Well tolerated in animal research at multiple dose levels
- !Theoretical concern: excessive anti-apoptotic activity could theoretically support tumor survival (not observed in research)
Potential Interactions
- ⚡May interact with IGF-1/IGFBP-3 axis — caution in patients on growth hormone therapy.
- ⚡Theoretical additive effects with other neuroprotective agents.
- ⚡Anti-apoptotic mechanism; theoretical concern with cancer biology (not clinically observed).
- ⚡May complement other mitochondrial support compounds (SS-31, CoQ10, NAD+).
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
A neuroprotective peptide encoded in the mitochondrial genome
Original discovery of humanin as a mitochondrial-encoded peptide that protects neurons against Alzheimer's disease-related amyloid-beta toxicity and multiple apoptotic insults.
Humanin directly binds BAX to prevent apoptosis
Demonstrated humanin directly binds the pro-apoptotic protein BAX, preventing its mitochondrial translocation and blocking the intrinsic apoptotic cascade.
Humanin improves insulin sensitivity and metabolic function
Showed humanin analogs improve insulin sensitivity, reduce visceral adiposity, and improve glucose tolerance in aged mice through IGFBP-3 displacement and central hypothalamic action.
Circulating humanin declines with age and correlates with health
Demonstrated age-related decline in circulating humanin levels in humans and established correlation between humanin levels and metabolic health, cognitive function, and longevity markers.
Mitochondrial-derived peptides: a new class of health regulators
thorough review of the MDP family including humanin, MOTS-c, and SHLPs, establishing mitochondrial-derived peptides as a new category of endocrine signals.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
Humanin is a 24-amino acid peptide encoded in the mitochondrial genome — the founding member of mitochondrial-derived peptides (MDPs). It protects against Alzheimer's, prevents apoptosis, improves insulin sensitivity, and declines with age. HNG (S14G-Humanin) is a 1,000x more potent synthetic analog.
SS-31 stabilizes mitochondrial membrane structure (cardiolipin). Humanin is a signaling peptide produced BY mitochondria that activates cellular survival programs. They work through completely different mechanisms, SS-31 improves mitochondrial function, humanin communicates mitochondrial status to the cell.
Yes. Plasma humanin levels drop significantly with aging, correlating with reduced cytoprotective capacity, insulin resistance, and cognitive decline. This age-related decline may represent loss of a critical mitochondrial retrograde survival signal.
Not yet. Humanin is in preclinical/early translational research. The related MDP MOTS-c has entered human clinical trials, potentially paving regulatory pathways for humanin. Research-grade humanin and HNG are available for laboratory use.
This is a theoretical concern since humanin is anti-apoptotic. However, research has not shown tumor-promoting effects, and some studies suggest humanin's metabolic and anti-inflammatory benefits may actually reduce cancer risk. This remains an active area of investigation.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.