Humanin
Mitochondria-Derived Peptide | HN
Humanin was the first mitochondria-derived peptide (MDP) discovered, originally cloned from the occipital lobe of an Alzheimer's patient. It is a 24-amino acid peptide encoded from the 16S rRNA region of mitochondrial DNA with potent neuroprotective, cytoprotective, and anti-apoptotic properties. Research shows humanin levels decline with age but remain stable in long-lived species like naked mole-rats, and offspring of centenarians have significantly higher humanin levels.
Mechanism of Action
Humanin exerts its effects through multiple mechanisms. It interacts with cell surface receptors including FPRL1 and CNTFR, activating PI3K/AKT signaling pathways that promote cell survival. It blocks pro-apoptotic proteins like Bax, reduces beta-amyloid toxicity in neurons, protects against oxidative stress, and promotes mitochondrial biogenesis. These actions support healthy cellular aging at a fundamental level.
Key Benefits
- Potent neuroprotection against Alzheimer's and Parkinson's pathology
- Extended lifespan in animal models (C. elegans)
- Improved metabolic healthspan parameters
- Reduced inflammatory markers
- Cytoprotective effects across multiple cell types
- Anti-apoptotic activity
- Mitochondrial optimization and biogenesis
- Protection against oxidative stress
MAPRGFSCLLLLTSEIDLPVKRRAMethionine
Position 1
Alanine
Position 2
Proline
Position 3
Arginine
Position 4
Glycine
Position 5
Phenylalanine
Position 6
Serine
Position 7
Cysteine
Position 8
Leucine
Position 9
Leucine
Position 10
Leucine
Position 11
Leucine
Position 12
Threonine
Position 13
Serine
Position 14
Glutamic Acid
Position 15
Isoleucine
Position 16
Aspartic Acid
Position 17
Leucine
Position 18
Proline
Position 19
Valine
Position 20
Lysine
Position 21
Arginine
Position 22
Arginine
Position 23
Alanine
Position 24
Neuroprotection
- Alzheimer's Disease Protection
Originally discovered for its ability to protect against amyloid-β toxicity in neuronal cells.
- Parkinson's Disease Support
Promotes mitochondrial biogenesis via PI3K/AKT signaling in PD models.
- General Neuroprotection
Broad neuroprotective effects against various neurotoxic insults.
Longevity
- Lifespan Extension
Overexpression increases lifespan in C. elegans, dependent on daf-16/Foxo pathway.
- Healthspan Improvement
HNG analog improves metabolic healthspan parameters in middle-aged mice.
- Anti-Aging
Higher levels associated with longevity in centenarians and their offspring.
Cellular Protection
- Cytoprotection
Protects various cell types from stress-induced damage and death.
- Anti-Apoptosis
Blocks pro-apoptotic proteins like Bax to prevent programmed cell death.
- Mitochondrial Support
Promotes mitochondrial function and biogenesis.
Subcutaneous or intravenous injection. Benefits are slow-building and cellular, typically felt over weeks to months as the peptide supports mitochondria and reduces oxidative stress. The more potent analog HNG (glycine substitution at position 14) is 1000-fold more potent than native humanin.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Neuroprotection | 1-5 mg | 2-3x weekly | SubQ |
| Longevity/Anti-aging | 1-3 mg | 2x weekly | SubQ |
| HNG analog | 0.5-2 mg | 2x weekly | SubQ |
Reconstitution Instructions
- Bacteriostatic water (BAC)
- Insulin syringes (0.5-1 mL)
- Alcohol swabs
- Peptide vial
- Sterile work surface
- 1 Clean work area and hands thoroughly
- 2 Calculate required BAC water volume
- 3 Draw BAC water into syringe
- 4 Inject slowly down vial side (not directly onto powder)
- 5 Gently swirl until dissolved (never shake)
- 6 Store in refrigerator, protect from light
Both are mitochondria-derived peptides with complementary longevity and metabolic benefits.
Both target mitochondrial function; may have additive benefits for cellular health.
Different mechanisms; can be combined in longevity protocols.
Both support mitochondrial function and healthy aging.
Subtle; peptide begins working at cellular level
Improved energy and reduced fatigue may begin
Enhanced cellular resilience and stress response
Cumulative benefits in mitochondrial function and healthspan markers
Potential longevity and neuroprotective benefits
Common Side Effects
- Injection site reactions
- Mild fatigue initially
- Headache (rare)
Stop Signs - Discontinue if:
- Signs of allergic reaction
- Unusual persistent symptoms
Contraindications
- Active cancer (theoretical concern with anti-apoptotic effects)
- Pregnancy or breastfeeding
- Hypersensitivity to peptide components
Good Signs
- White to off-white lyophilized powder
- Clear solution after reconstitution
- Intact vacuum seal
Warning Signs
- Slight clumping that dissolves easily
Bad Signs
- Discolored powder
- Cloudy or particulate solution
- Broken seal
- The mitochondrial derived peptide humanin is a regulator of lifespan and healthspanAging (2020)
Humanin overexpression extends lifespan in C. elegans; HNG treatment improves metabolic healthspan in middle-aged mice; levels higher in centenarian offspring.
- Neuroprotective Action of Humanin and Humanin AnaloguesBiology (MDPI) (2023)
Comprehensive review of humanin's neuroprotective effects in Alzheimer's and Parkinson's disease models.
- Mitochondria-derived peptides in aging and healthspanJournal of Clinical Investigation (2022)
Review of mitochondria-derived peptides including humanin and their roles in aging and metabolic health.
- Original Discovery of HumaninProceedings of the National Academy of Sciences (2001)
Hashimoto et al. cloned humanin from Alzheimer's patient brain; demonstrated protection against amyloid-β toxicity.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.