Humanin
Also known as: HN, HNG (S14G-humanin), [Gly14]-Humanin
Grey-Market Compound. This compound is not approved by the FDA or any major regulatory authority. No established regimen exists. Products available outside of regulated channels lack standardized manufacturing, quality control, and potency verification. Consult a qualified clinician. Research-only risks apply.
Overview
Clinical Summary
Humanin is a 24-amino acid peptide encoded by a short open reading frame within the mitochondrial 16S rRNA gene. It was discovered in 2001 as a factor that suppresses neuronal cell death induced by Alzheimer disease-related insults. Humanin and its more potent analogue HNG (S14G-humanin) have demonstrated cytoprotective effects across multiple preclinical disease models including neurodegenerative disease, cardiovascular injury, and metabolic dysfunction. Circulating humanin levels decline with age and are inversely correlated with age-related disease. No human clinical trials have been conducted.
Plain Language Summary
Humanin is a naturally occurring peptide made by your mitochondria that protects cells from dying. It was discovered through Alzheimer disease research, where it was found to prevent brain cell death. Studies in animals suggest it could protect the heart, brain, and metabolic systems. Humanin levels naturally drop as you age. While promising in laboratory studies, it has not been tested in human clinical trials and remains a research-only compound.
Mechanism of Action
Humanin exerts cytoprotective effects through multiple mechanisms. It binds to IGFBP-3, preventing IGFBP-3-induced apoptosis. It activates the formyl peptide receptor-like 1 (FPRL1/FPR2), triggering anti-apoptotic signaling through STAT3 phosphorylation and ERK1/2 activation. Humanin also interacts with BAX, preventing BAX-mediated mitochondrial membrane permeabilization and cytochrome c release. In metabolic tissues, humanin enhances insulin sensitivity through central and peripheral mechanisms. The S14G substitution (HNG) increases potency approximately 1,000-fold. Humanin has also been shown to reduce oxidative stress, inhibit inflammatory cytokine production, and promote cellular autophagy.
Evidence Summary
Hashimoto et al. (2001) discovered humanin and demonstrated neuroprotection against multiple familial AD gene products in vitro. Subsequent preclinical studies showed: cardioprotection against ischemia-reperfusion injury in mice, improved insulin sensitivity in diabetic mouse models, reduced atherosclerotic plaque formation in ApoE-knockout mice, and attenuation of chemotherapy-induced cognitive dysfunction. Epidemiological data show that higher circulating humanin levels correlate with better cardiometabolic health and longevity. No interventional human studies have been conducted.
Safety Profile
No human safety data exist. Preclinical studies have not identified significant toxicity. As an endogenous peptide, humanin is expected to have a favorable safety profile, but this assumption has not been tested in human dosing studies. The short plasma half-life of native humanin may limit systemic exposure but also limits therapeutic utility without modified analogues.
Contraindications
- No established contraindications due to absence of human data
- Theoretical concern in active malignancy (anti-apoptotic effects could protect cancer cells)
- Pregnancy and breastfeeding (no safety data)
Adverse Events
- No human adverse event data available
- Theoretical risk that anti-apoptotic activity could protect malignant cells
- Unknown systemic effects of exogenous administration
Interactions
- No drug interaction data available
- Theoretical interaction with IGF-1 signaling modulators (via IGFBP-3 binding)
- May interact with chemotherapy agents (anti-apoptotic mechanism)
Regulatory Notes
Humanin is a research-only compound with no regulatory approval in any jurisdiction. It has not entered clinical trials as a therapeutic agent. Academic research continues at multiple institutions including USC, Albert Einstein College of Medicine, and others. Modified analogues (HNG) are being explored for potential clinical development.
Monitoring Considerations
No established monitoring guidelines. In a research context, metabolic markers (fasting glucose, insulin, HOMA-IR), inflammatory markers (CRP, IL-6), and neurocognitive assessments could be considered. Circulating humanin levels can be measured via ELISA.
These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.
Stability and Handling Notes
Research-grade humanin is supplied as lyophilized powder. Native humanin has a short plasma half-life. Store lyophilized at minus 20 degrees C. Reconstitute in sterile water or PBS. Modified analogues (HNG) may have improved stability. Not commercially available outside research supply channels.
References
- 1preclinical
Humanin, a Peptide Encoded by a Mitochondrial Gene, Suppresses Apoptosis Induced by Alzheimer Disease-Associated Genes
Hashimoto Y, Niikura T, Tajima H, et al. (2001). Proceedings of the National Academy of Sciences
Key findings: Discovery paper demonstrating that humanin suppresses neuronal cell death induced by multiple familial Alzheimer disease genes and amyloid-beta peptide in vitro.
Limitations: In vitro study. Initial characterization only. Therapeutic translation not addressed.
View source - 2review
Humanin: A Mitochondrial Signaling Peptide for Cytoprotection and Metabolic Regulation
Cobb LJ, Lee C, Xiao J, et al. (2016). Free Radical Biology and Medicine
Key findings: Review covering humanin biology including IGFBP-3 binding, FPRL1 receptor activation, and STAT3 signaling. Summarizes cytoprotective effects across cardiovascular, neurological, and metabolic disease models.
Limitations: Entirely preclinical data at time of review. No human clinical trials initiated.
View source
Last reviewed: 2026-03-24 | Version: 1 | Status: Published
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