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Humanin

(HN)
Anti-AgingResearch Onlypreliminary evidenceTrack This Protocol
PN

Reviewed by Peptide Nerds Editorial · Updated March 2026

Key Takeaway

Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of mitochondrial DNA. Discovered in 2001, it was the first identified MDP and has demonstrated neuroprotective, cytoprotective, and metabolic regulatory properties in preclinical research. It is being studied for its role in Alzheimer disease, type 2 diabetes, and age-related decline.

Quick Facts
TypeAnti-Aging
FDA StatusResearch Only
Evidence LevelPreliminary
Typical DoseNo established human dose
FrequencyExperimental only
Key Goalscognitive, anti-aging

How it works

Humanin exerts its effects through multiple pathways. It binds to the FPRL1 receptor (formyl peptide receptor-like 1) and the trimeric receptor complex consisting of CNTFR, WSX-1, and gp130, activating STAT3 signaling. It also interacts directly with Bax protein to inhibit mitochondrial apoptosis, and with IGFBP-3 to modulate IGF-1 signaling. These pathways collectively protect cells from stress-induced death, reduce inflammation, and improve insulin sensitivity.

Benefits

  • Neuroprotection against amyloid-beta toxicity in Alzheimer disease models
  • Anti-apoptotic effects through direct Bax protein inhibition
  • Improved insulin sensitivity and glucose metabolism in animal models
  • Cytoprotection against oxidative stress and mitochondrial dysfunction
  • Reduced atherosclerotic plaque formation in mouse models
  • Circulating levels correlate with longevity in human centenarian studies

Side effects

  • Very limited human safety data
  • Potential interaction with IGF-1 signaling pathways
  • Unknown long-term effects
  • No standardized pharmaceutical formulation exists

Dosing protocol

Typical Dose

No established human dose

Frequency

Experimental only

Humanin is primarily studied in preclinical settings (cell culture and animal models). A synthetic analog called HNG (S14G-humanin) has shown enhanced potency in research. No human clinical trials have established dosing protocols. Circulating humanin levels decline with age, which has prompted interest in supplementation, but delivery methods and dosing remain entirely experimental. Intranasal and subcutaneous routes have been used in animal studies.

What you will need

Basic supplies for reconstitution and subcutaneous injection.

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Key research

Humanin, a newly identified neuroprotective factor

Journal of Biological Chemistry (2001)PubMed

First identification of humanin as a mitochondrial-derived peptide that protects neuronal cells from Alzheimer disease-associated toxicity.

The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways

Journal of Biological Chemistry (2009)PubMed

Demonstrated humanin signals through FPRL1 and the trimeric CNTFR/WSX-1/gp130 receptor complex, activating STAT3 and pro-survival pathways.

Humanin and age-related diseases: a new link?

Frontiers in Endocrinology (2018)PubMed

Review demonstrating that circulating humanin levels decline with age and correlate inversely with metabolic disease markers, supporting its role as a longevity biomarker.

Mitochondrial-derived peptide humanin improves insulin sensitivity

American Journal of Physiology (2014)PubMed

Humanin treatment improved insulin sensitivity in high-fat diet mouse models, with effects mediated through STAT3 signaling in skeletal muscle.

Circulating levels of humanin in centenarians

Aging Cell (2020)PubMed

Centenarians and their offspring maintain higher circulating humanin levels compared to age-matched controls, suggesting a role in exceptional longevity.

Humanin prevents age-related cognitive decline in mice and is associated with improved cognitive age in humans

Scientific Reports (2018)PubMed

Intracerebroventricular humanin administration improved cognitive performance in aged mice. In humans, higher humanin levels correlated with better cognitive function.

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Frequently asked questions

Humanin is a 24-amino-acid peptide encoded in mitochondrial DNA. It was discovered in 2001 as the first mitochondrial-derived peptide (MDP) and has shown neuroprotective, anti-apoptotic, and metabolic regulatory properties in laboratory and animal research.

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Medical Disclaimer: This content is for informational and educational purposes only. It is not intended as medical advice or a substitute for professional medical consultation, diagnosis, or treatment. Always consult a qualified healthcare provider before starting any peptide protocol.