Also known as: HN, HNG, S14G-HN, MT-RNR2
Neuroprotection and anti-aging research
Amount
5 mg/kg/day IP (S14G-HNG analog, preclinical)
Frequency
Daily (animal studies)
Duration
3 months (primary study)
Route
SCTiming
Animal studies used intraperitoneal or intracerebroventricular routes. S14G-humanin (HNG) analog is approximately 1000-fold more potent than native humanin.
Duration
3 months (preclinical)
Repeatable
Single cycle
CBC with differential
When: Baseline
Why: Baseline blood cell counts
CMP (Comprehensive Metabolic Panel)
When: Baseline
Why: Liver and kidney function baseline
Fasting glucose and insulin
When: Baseline
Why: Humanin affects insulin sensitivity and glucose homeostasis
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Humanin is a 24-amino acid peptide encoded within the mitochondrial genome, specifically by a small open reading frame in the MT-RNR2 gene (16S ribosomal RNA region). It was discovered in 2001 by Hashimoto and colleagues who screened a cDNA library from surviving neurons in an Alzheimer's disease brain, identifying a factor that could rescue neuronal cells from death induced by multiple familial Alzheimer's disease genes and amyloid-beta.
Humanin was the first member of a now-recognized class of mitochondrial-derived peptides (MDPs) that also includes MOTS-c and small humanin-like peptides (SHLPs 1-6). These peptides are encoded by short open reading frames within mitochondrial DNA and function as retrograde signaling molecules from mitochondria to the cell and beyond.
Humanin exerts its effects through both extracellular and intracellular mechanisms:
Extracellular signaling: Humanin is secreted and binds to a heterotrimeric receptor complex consisting of CNTFR-alpha (ciliary neurotrophic factor receptor), WSX-1 (IL-27 receptor alpha), and gp130 (glycoprotein 130). This activates downstream JAK2/STAT3 and PI3K/AKT survival signaling cascades.
Intracellular actions: Within the cell, humanin directly interacts with the pro-apoptotic Bcl-2 family members Bax and BID, preventing their oligomerization at the mitochondrial membrane and blocking cytochrome c release and the intrinsic apoptotic pathway.
IGFBP-3 interaction: Humanin also binds insulin-like growth factor binding protein 3 (IGFBP-3), modulating the IGFBP-3/IGF-I axis and contributing to its metabolic and cytoprotective effects.
Preclinical evidence supports humanin's protective effects across multiple disease models including Alzheimer's disease, cardiovascular disease, diabetes, and age-related macular degeneration. The potent analog S14G-humanin (HNG) has demonstrated cognitive improvement and amyloid reduction in transgenic Alzheimer's mouse models. Circulating humanin levels decline with age and correlate inversely with markers of metabolic disease, suggesting a role in aging biology.
Humanin remains entirely preclinical with no completed human trials. A significant concern for clinical translation is evidence that humanin may promote tumor cell survival and chemoresistance through the same anti-apoptotic mechanisms that provide neuroprotection. The balance between cytoprotective benefits and potential oncogenic risks requires further investigation before clinical development can proceed.
A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and amyloid-beta, published in Proceedings of the National Academy of Sciences (Hashimoto Y et al., 2001; PMID: 11381134):
Original discovery of humanin. Screened a cDNA library from surviving neurons in an Alzheimer's disease occipital lobe and identified a 24-amino acid peptide that rescued neuronal cells from death induced by multiple familial AD genes and amyloid-beta.
S14G-humanin improves cognitive deficits and reduces amyloid pathology in the middle-aged APPswe/PS1dE9 mice, published in Pharmacology Biochemistry and Behavior (Zhang W et al., 2012; PMID: 21993310):
Chronic treatment with S14G-humanin (HNG) at 5 mg/kg/day IP for 3 months improved spatial memory and reduced amyloid pathology in middle-aged transgenic AD mice.
Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130, published in Molecular Biology of the Cell (Hashimoto Y et al., 2009; PMID: 19386761):
Identified the tripartite receptor complex for humanin consisting of CNTFR-alpha, WSX-1, and gp130. Humanin induced hetero-oligomerization of these receptors to activate neuroprotective signaling.
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This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.
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