Humanin
Humanin (HN): mitochondrial-derived peptide
24-amino-acid peptide encoded within the mitochondrial 16S rRNA gene, discovered 2001 by Hashimoto et al. via functional cloning of cDNA from an Alzheimer's brain occipital lobe. Originally identified as a rescue factor against Aβ- and FAD-mutant-induced neuronal death; now studied as a broader cytoprotective and longevity peptide. Endogenous humanin levels decline with age and correlate with cognitive performance in humans. The S14G analog (HNG) is ~1000x more potent than native humanin and is the form used in most preclinical studies.
At a glance
- Half-life
- ~30 min Native humanin t½ ~30 minutes. The S14G analog (HNG) is ~1000x more potent and has extended half-life. AGA-(C8R)HNG-17 (Colivelin) is the most potent research analog. No human exogenous PK published.
- Routes
- SubQ · IV
- Vial sizes
- 5 mg · 10 mg
- Evidence base
- 3 studies 1 human · 1 review · 1 preclinical
Mechanism
Binds and inhibits pro-apoptotic Bax, blocking mitochondrial outer membrane permeabilization and cytochrome c release. Suppresses ASK1/JNK signaling. Also signals through extracellular receptors (FPR2, gp130/CNTFR/WSX-1 trimeric receptor) to activate STAT3 survival signaling. Original discovery: cDNA encoding 24aa humanin peptide rescued neurons from Aβ-induced death and from APP/PS1/PS2 FAD mutant toxicity. Endogenously produced in human tissues with measurable circulating levels. HNG analog reversed age-related cognitive decline in mice; circulating humanin in humans correlates with better cognitive performance. Reduces neuroinflammation by inhibiting microglial activation; improves insulin sensitivity in some animal models.
Dosing
Any amounts shown here are reported from published studies only. 1 of 3 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.
Published evidence
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Human observational 2002
Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults
Confirmed humanin is endogenously produced in human tissues; circulating levels measurable.
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Review 2001
A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta
Original discovery: cDNA encoding 24aa humanin peptide rescued neurons from Aβ-induced death and from APP/PS1/PS2 FAD mutant toxicity.
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Animal in vivo 2018
Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans
HNG analog reversed age-related cognitive decline in mice; circulating humanin in humans correlates with better cognitive performance.
Reported side effects
- Injection site reaction
- Common Mild · Local redness, mild stinging.
- Transient fatigue
- Occasional Mild · Reported during early dosing weeks.
- Theoretical insulin sensitivity changes
- Rare Mild · Mechanistic: humanin improves insulin sensitivity in animal models. Relevant for diabetics on insulin.
Interactions
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Insulin Caution
Humanin improves insulin sensitivity. Diabetics on insulin may need dose adjustment.
Reconstitution and storage
Reconstitute with bacteriostatic water. 5mg vial + 2mL BAC water → 2.5 mg/mL. Gentle swirl, do not shake.
Lyophilized: -20°C long term. Reconstituted: refrigerate 2-8°C, use within 30 days.