COMPOUND

Compounds / Anti-aging

Humanin

Humanin (HN): mitochondrial-derived peptide

Anti-aging SubQ · IV Not FDA approved

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

  1. Human observational 2002

    Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults

    Tajima H, Kawasumi M, Chiba T, et al. Neuroscience Letters

    Confirmed humanin is endogenously produced in human tissues; circulating levels measurable.

    PMID 12009529

  2. Review 2001

    A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta

    Hashimoto Y, Niikura T, Tajima H, et al. PNAS

    Original discovery: cDNA encoding 24aa humanin peptide rescued neurons from Aβ-induced death and from APP/PS1/PS2 FAD mutant toxicity.

    PMID 11371646

  3. Animal in vivo 2018

    Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans

    Yen K, Wan J, Mehta HH, et al. Scientific Reports

    HNG analog reversed age-related cognitive decline in mice; circulating humanin in humans correlates with better cognitive performance.

    PMID 30242290

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

  • 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.