Humanin
Mitochondria-Derived PeptideresearchAlso known as: HN, HNG (S14G-Humanin), Humanin G, rHumanin
A mitochondria-derived 24-amino acid peptide with potent cytoprotective and neuroprotective effects, being studied for Alzheimer's disease, metabolic health, and longevity.
Overview
Humanin is a 24-amino acid peptide encoded by the mitochondrial genome (MT-RNR2 gene within the 16S ribosomal RNA). Discovered in 2001 from a screen of genes that protect neurons from Alzheimer's disease-related toxicity, humanin has since been found to play broader roles in cellular survival, metabolic regulation, and stress resistance. It circulates in blood and cerebrospinal fluid, and its levels decline with age — correlating with age-related diseases. Humanin acts as an endogenous cytoprotective factor, protecting cells from apoptosis induced by various stressors including amyloid beta, oxidative stress, and serum starvation. The synthetic analog HNG (S14G-Humanin) is ~1000-fold more potent than native humanin. Research suggests humanin may be a key mediator of the mitochondrial-nuclear communication axis relevant to aging and longevity, with higher levels associated with longer lifespan across species.
Mechanism of Action
Humanin exerts cytoprotection through multiple pathways: (1) Binds to and activates the FPRL1/FPRL2 (formyl peptide receptor-like) receptors, triggering pro-survival signaling; (2) Interacts with IGFBP-3, blocking IGFBP-3-induced apoptosis; (3) Binds to BAX protein, preventing BAX-mediated mitochondrial apoptosis; (4) Activates the STAT3 signaling pathway, promoting cell survival genes; (5) Enhances insulin sensitivity by activating the AMPK pathway; (6) Reduces endoplasmic reticulum stress and unfolded protein response; (7) Acts as a retrograde signal from mitochondria to nucleus, coordinating stress responses; (8) Protects against amyloid beta neurotoxicity through direct binding to Aβ aggregates.
Molecular Formula
C105H170N34O33S2
Molecular Weight
2687.0 g/mol
Sequence
Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala
Dosage Protocols
Dose Range
1mg – 5mg
Frequency
Daily
Route
subcutaneous
Cycle Length
4-8 weeks (experimental)
No established human dosing. Animal studies use various doses; HNG analog (S14G-Humanin) is ~1000x more potent than native humanin. Self-experimentation protocols vary widely. Consult research literature.
Source: Preclinical research extrapolation
Side Effects
| Effect | Severity |
|---|---|
| Largely unknown in humans | unknown |
| Injection site irritation | mild |
| Potential IGF interaction | unknown |
Pros & Cons
Endogenously produced mitochondrial peptide with fundamental roles in cellular survival and stress resistance
Potent neuroprotective effects against Alzheimer's-related amyloid beta toxicity
Circulating levels correlate with longevity across species, suggesting a genuine aging biomarker
Multi-system benefits spanning neurological, metabolic, and cardiovascular protection
HNG analog provides 1000-fold potency enhancement, reducing required doses
No human clinical trials — all evidence is preclinical or observational
Human dosing and pharmacokinetics are not established
Interaction with the IGF/insulin axis raises theoretical concerns about long-term supplementation effects
Limited availability and high cost for research-grade peptide
Research Studies
Legal Status
Not approved by any regulatory agency. Available as a research peptide. No clinical trials completed in humans. Investigational compound for Alzheimer's disease and metabolic disorders.
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