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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.
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.
MAPRGFSCLLLLTSEIDLPVKRRA
Methionine
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
Originally discovered for its ability to protect against amyloid-β toxicity in neuronal cells.
Promotes mitochondrial biogenesis via PI3K/AKT signaling in PD models.
Broad neuroprotective effects against various neurotoxic insults.
Overexpression increases lifespan in C. elegans, dependent on daf-16/Foxo pathway.
HNG analog improves metabolic healthspan parameters in middle-aged mice.
Higher levels associated with longevity in centenarians and their offspring.
Protects various cell types from stress-induced damage and death.
Blocks pro-apoptotic proteins like Bax to prevent programmed cell death.
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 |
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
Aging
Humanin overexpression extends lifespan in C. elegans; HNG treatment improves metabolic healthspan in middle-aged mice; levels higher in centenarian offspring.
Biology (MDPI)
Comprehensive review of humanin's neuroprotective effects in Alzheimer's and Parkinson's disease models.
Journal of Clinical Investigation
Review of mitochondria-derived peptides including humanin and their roles in aging and metabolic health.
Proceedings of the National Academy of Sciences
Hashimoto et al. cloned humanin from Alzheimer's patient brain; demonstrated protection against amyloid-β toxicity.
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