Humanin (HN) — Mitochondrial-Derived Peptide
Also Known AsHN · HNG · S14G-Humanin · [Gly14]-Humanin
Discovered in 2001 by Nishimoto and colleagues at Keio University, Tokyo, from a cDNA library screen of surviving neurons in an Alzheimer's disease brain. Humanin is encoded by the mitochondrial 16S rRNA gene (MT-RNR2) and was the first identified mitochondrial-derived peptide (MDP). The synthetic analog HNG (S14G-Humanin) exhibits approximately 1000-fold greater cytoprotective potency.
Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-AlaHow Humanin Works
STAT3 Signaling Activation
Humanin binds the trimeric receptor complex comprising CNTFR/WSX-1/gp130 on the cell surface, triggering JAK1/2 phosphorylation and downstream STAT3 activation. This promotes transcription of anti-apoptotic genes including Bcl-2 and Mcl-1, protecting cells from apoptosis.
IGFBP-3 Interaction
Directly binds insulin-like growth factor binding protein-3 (IGFBP-3) and the pro-apoptotic protein Bax. By sequestering IGFBP-3 and preventing Bax translocation to the mitochondrial membrane, humanin blocks cytochrome c release and caspase-9 activation.
AMPK Signaling
Activates AMP-activated protein kinase (AMPK) in peripheral tissues, enhancing cellular energy sensing. AMPK activation promotes fatty acid oxidation, glucose uptake, and mitochondrial biogenesis while suppressing mTORC1-mediated anabolic signaling.
Formyl Peptide Receptor 2 (FPR2/ALX)
Binds and signals through FPR2/ALX receptors, promoting resolution of inflammation through enhanced efferocytosis and reduced NF-kappaB-dependent cytokine production. This pathway contributes to humanin's anti-inflammatory effects in vascular and neuronal tissues.
Published Research
Neuroprotection & Alzheimer's Disease
StrongHumanin was originally isolated for its ability to rescue neurons from amyloid-beta (Abeta) toxicity. In vitro and in vivo studies demonstrate protection against Abeta1-42 and Abeta1-43-induced apoptosis, presenilin mutant-associated cell death, and familial AD-linked insults. The HNG analog shows nanomolar efficacy in neuronal survival assays.
Metabolic Regulation & Insulin Sensitivity
ModerateSystemic administration of HNG in murine models improves insulin sensitivity, reduces hepatic glucose output, and lowers circulating triglycerides. Circulating humanin levels inversely correlate with age and BMI in human cohort studies. AMPK activation in skeletal muscle and liver mediates the metabolic effects.
Cardiovascular Protection
ModeratePreclinical models of myocardial ischemia-reperfusion injury demonstrate reduced infarct size and improved cardiac function with humanin treatment. The cardioprotective mechanism involves STAT3-mediated anti-apoptosis and reduced oxidative stress via enhanced mitochondrial electron transport chain efficiency.
Cellular Aging & Senescence
EmergingHumanin levels decline with age across species. Exogenous humanin administration reduces markers of cellular senescence (p16INK4a, SA-beta-gal) in aged murine tissues and enhances mitochondrial membrane potential in senescent fibroblasts. The MOTS-c and SHLP family of MDPs share overlapping longevity-associated mechanisms.
Inflammatory Bowel Disease
PreclinicalFPR2-mediated anti-inflammatory signaling positions humanin as a candidate for intestinal inflammation research. Preclinical colitis models show reduced mucosal inflammation, lower TNF-alpha and IL-6, and improved epithelial barrier integrity with humanin treatment.
Safety Profile
Humanin is an endogenously produced peptide with no reported toxicity in preclinical studies across multiple animal models. Circulating humanin is present in human plasma at picomolar concentrations. Exogenous administration in rodent models at doses up to 10 mg/kg has shown no adverse effects on organ histology, hematology, or behavior. No human clinical trial safety data are available.
Handling & Storage
Reconstitute with bacteriostatic water. Direct gentle stream along vial wall — do not shake. Store reconstituted solution at 2-8°C and use within 28 days. Lyophilized powder stable at -20°C for 24+ months. Avoid repeated freeze-thaw cycles.
Peer-Reviewed Literature
- 1
A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta
Hashimoto Y, Niikura T, Tajima H, et al.
- 2
Humanin peptide suppresses apoptosis by interfering with Bax activation
Guo B, Zhai D, Cabezas E, et al.
- 3
Humanin: a novel central regulator of peripheral insulin action
Muzumdar RH, Huffman DM, Atzmon G, et al.
- 4
The emerging role of the mitochondrial-derived peptide humanin in stress resistance
Yen K, Lee C, Mehta H, Cohen P.
- 5
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
Lee C, Zeng J, Drew BG, et al.
Humanin FAQ
What is humanin?
Humanin is a 24-amino acid peptide encoded by the mitochondrial genome (MT-RNR2 gene in the 16S rRNA region). Discovered in 2001 from surviving neurons in an Alzheimer's disease brain, it was the first identified mitochondrial-derived peptide (MDP) and has demonstrated cytoprotective, metabolic, and anti-inflammatory properties in preclinical research.
What is the difference between humanin and HNG?
HNG (also called S14G-Humanin or [Gly14]-Humanin) is a synthetic analog with a serine-to-glycine substitution at position 14. This modification confers approximately 1000-fold greater cytoprotective potency compared to native humanin, making it the preferred form for research applications.
How does humanin relate to MOTS-c?
Both humanin and MOTS-c belong to the mitochondrial-derived peptide (MDP) family — small bioactive peptides encoded within mitochondrial DNA. While humanin is encoded in the 16S rRNA gene and acts primarily through STAT3 and IGFBP-3 pathways, MOTS-c is encoded in the 12S rRNA gene and acts primarily through AMPK. Both decline with age and are implicated in longevity research.
What is the purity of G26x Peptides humanin?
Our humanin is 99%+ purity, independently verified by Janoshik Analytical with a full Certificate of Analysis (COA) available for each batch. It is supplied as a lyophilized powder manufactured under GMP-adjacent conditions.
How should humanin be stored?
Lyophilized humanin should be stored at -20°C for long-term storage (stable for 24+ months). Once reconstituted with bacteriostatic water, store at 2-8°C (refrigerator) and use within 28 days. Avoid repeated freeze-thaw cycles.
Humanin Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
Humanin
5mgYour mitochondria's SOS signal — a survival peptide that protects brain cells, heart tissue, and metabolic function from age-related stress and damage.
- Protects cells from stress-induced death (apoptosis)
- Strong neuroprotective effects against Alzheimer's markers
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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.