Humanin

Mitochondrial-Derived Cytoprotective Peptide

Half-life: ~minutes (native); HNG variant more stable

HNHumanin G (HNG — Gly14 variant)

Research Profile

Research Depth

Potency

Half-Life Score

Selectivity

Stability

Relative research assessments — educational reference only.

Target Receptors

FPRL1gp130/CNTFR/WSX-1 complexSTAT3 pathway

Critical Research Warning

For educational reference only. Native Humanin has extremely short half-life. HNG (Gly14) variant is more stable for research use. No human trials for any indication.

PeptidePlaza Entry #018

"A 21-amino acid mitochondria-encoded peptide discovered through its ability to rescue neurons from Alzheimer's-related death. Like MOTS-c, it belongs to the emerging class of mitochondrial-derived peptides with systemic metabolic and cytoprotective effects."

Full Description

Humanin is a 21-amino acid peptide encoded in the 16S rRNA region of the mitochondrial genome, discovered in 2001 by Nishimoto et al. while screening for factors that rescue neurons from Alzheimer's disease-related apoptosis. It acts via multiple receptors (FPRL1, gp130/CNTFR/WSX-1 tripartite receptor complex) to exert cytoprotective, anti-apoptotic, and metabolic effects. Circulating Humanin levels decline significantly with age. Research links it to improved insulin sensitivity (via STAT3), neuroprotection, sperm protection against apoptosis, cardiovascular protection, and life extension in animal models.

Mechanism of Action

Binds FPRL1 and the gp130/CNTFR/WSX-1 receptor complex. Activates STAT3 and PI3K/Akt survival pathways. Inhibits BAX-mediated apoptosis. Reduces mitochondrial ROS. Improves peripheral insulin sensitivity via hypothalamic STAT3 signaling.

Reported Benefits

• Neuroprotection against Alzheimer's-related amyloid toxicity
• Improved insulin sensitivity via STAT3 pathway
• Anti-apoptotic effects across multiple tissue types

Potential Side Effects

• Rapid degradation (native form) — limited bioavailability
• Injection site reactions
• Long-term human side-effect profile unknown

Frequently Asked Questions

What makes Humanin significant in neurodegeneration research?▼

Humanin was the first peptide shown to rescue neurons from Alzheimer's-related cell death, making it a landmark compound in the study of mitochondrial-to-nuclear cytoprotective signaling. It acts through unique receptor complexes not targeted by current Alzheimer's drugs.

How do Humanin levels change with age?▼

Circulating Humanin levels drop 30–50% between ages 20–70, making it one of the steepest age-related declines of any known peptide. This age-related depletion correlates with increased insulin resistance, cardiovascular disease, and cognitive decline.

For Research Reference Only

Not medical advice. Peptides may be regulated or restricted in your jurisdiction.

References

1.Network Topology and Interactomic Analysis Reveal the Regulatory Framework of the Humanin Protein Family (MTRNR2Lx Class). PubMed (2026). Shahzaib M, et al.. pubmed.ncbi.nlm.nih.gov/42509775/ ↑
2.S14G-humanin (HNG) ameliorates diabetic nephropathy tubular injury by inhibiting Z-DNA/ZBP1-mediated necroptosis. PubMed (2026). Liu Y, et al.. pubmed.ncbi.nlm.nih.gov/42492881/ ↑
3.Humanin peptide ameliorates reproductive dysfunction and restores neuroendocrine mechanisms in SSRI-treated male rats. PubMed (2026). Köm Akipek RE, et al.. pubmed.ncbi.nlm.nih.gov/42480246/ ↑
4.Neuroprotective effect of intraperitoneal Humanin-G in retinal degeneration of Royal College of Surgeons rats. PubMed (2026). Lin B, et al.. pubmed.ncbi.nlm.nih.gov/42471450/ ↑