Overview

Humanin is a 21-amino acid mitochondrial-derived peptide (MDP) encoded by the 16S rRNA region of mitochondrial DNA. It was the first MDP discovered, originally identified in neurons surviving from Alzheimer's disease-affected brain tissue, and has since been shown to have cytoprotective, neuroprotective, and anti-aging effects across multiple tissues. Humanin levels decline with age and are reduced in diseases including Alzheimer's and MELAS syndrome. A potent analog, HNG (where Ser14 is replaced by Gly), shows approximately 1000-fold greater potency.

Mechanism of Action

Humanin acts through multiple receptors and pathways: (1) binding to trimeric receptor complexes including CNTFR, WSX-1, and gp130, activating JAK/STAT3 and MAPK/ERK1/2 signaling; (2) activation of AKT1 kinase promoting cell survival; (3) reduction of mitochondrial ROS, protecting against amyloid-beta mitochondrial toxicity; (4) boosting chaperone-mediated autophagy via lysosomal localization; (5) reduction of fibril formation and Aβ-induced toxicity; (6) reversal of cardiomyocyte apoptosis in aged hearts via reduction of mitochondrial dysfunction.

Potential Benefits

  • Neuroprotection against amyloid-beta and Alzheimer's-related toxicity
  • Prevention of age-related cognitive decline in mouse models
  • Cardioprotection including reversal of cardiomyocyte apoptosis in aging
  • Reduction in midlife adiposity and increased lean body mass
  • Mitochondrial ROS reduction
  • Small but significant lifespan extension in C. elegans via daf-16/FOXO pathway
  • Protection against heat-shock stress in yeast models
  • Potential Parkinson's disease neuroprotection

Dosage Protocols

The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.

Typical Range2-10 mg/week
Beginner2 mg once or twice weekly
Intermediate5 mg twice weekly
Advanced10 mg twice weekly; HNG (S14G-Humanin) analog effective at lower doses
Cycle Duration4-8 weeks
Cycle Off4 weeks

HNG (S14G-Humanin), the more potent analog, is active at approximately 100-1000x lower concentrations than native Humanin. Research protocols are extrapolated from preclinical data. Often combined with other mitochondrial peptides.

Routes of Administration

Subcutaneous Injection High

Primary research route; systemic cytoprotective and anti-apoptotic effects

Intramuscular Injection High

Alternative; comparable systemic distribution

Stacking Protocols

Popular research stacks involving Humanin:

Mitochondrial Longevity Stack

Mitochondria-targeted cytoprotection, energy optimization, and cellular aging reduction

Humanin reduces apoptosis, MOTS-c drives biogenesis and metabolism, SS-31 protects cristae integrity. Complementary mitochondrial targets.

Neuroprotection Stack

Multi-target neuroprotection against Alzheimer's pathology and neurodegeneration

Humanin directly inhibits Aβ cytotoxicity; Semax provides BDNF-driven neuroprotection; NAD+ supports neuronal mitochondrial function.

Reconstitution

Typical Vial Size5mg, 10mg
BAC Water1-2ml per 5mg vial
StorageRefrigerate at 2-8°C after reconstitution
Shelf Life28 days refrigerated

Need exact syringe measurements?

Amino Acid Sequence

MAPRGFSCLLLLTSEIDLPVKRRA (21 amino acids); HNG: MAPRGFSCLLLLTSEIDLPVKRRG (S14G substitution)

Side Effects & Safety

  • Minimal known adverse effects in preclinical studies
  • Theoretical growth-promoting effects via IGF-1 axis interaction
  • Limited human safety data

Synergistic Compounds

The following compounds have been studied alongside Humanin for potential complementary or synergistic effects:

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References & Further Reading

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