Humanin (HN)

Mitochondria-Derived Peptide | HN

Weight: 2,687 Da
Half-life: ~30 minutes (mice), >4 hours (rats)
Chain: 24 amino acids
4 studies
2023 latest
Moderate Research
Dose 1-5 mg per injection (0.5-2 mg for HNG analog)
Frequency 2-3 times weekly for sustained mitochondrial support
Cycle 8-12 weeks
Storage Lyophilized: Room temperature. Reconstituted: 2-8°C, protect from light

Community Research

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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.

01 Potent neuroprotection against Alzheimer's and Parkinson's pathology
02 Extended lifespan in animal models (C. elegans)
03 Improved metabolic healthspan parameters
04 Reduced inflammatory markers
05 Cytoprotective effects across multiple cell types
06 Anti-apoptotic activity
07 Mitochondrial optimization and biogenesis
08 Protection against oxidative stress

Molecular Data

Molecular Weight
2,687 Da
Chain Length
24 amino acids
Type
Mitochondria-derived peptide
Amino Acid Sequence
One-letter: MAPRGFSCLLLLTSEIDLPVKRRA
H₂N
M 1
O C
N
A 2
O C
N
P 3
O C
N
R 4
O C
N
H
G 5
O C
N
F 6
O C
N
S 7
O C
N
C 8
O C
N
L 9
O C
N
L 10
O C
N
L 11
O C
N
L 12
O C
N
T 13
O C
N
S 14
O C
N
E 15
O C
N
I 16
O C
N
D 17
O C
N
L 18
O C
N
P 19
O C
N
V 20
O C
N
K 21
O C
N
R 22
O C
N
R 23
O C
N
A 24
COOH
Met
1

Methionine

Position 1

Ala
2

Alanine

Position 2

Pro
3

Proline

Position 3

Arg
4

Arginine

Position 4

Gly
5

Glycine

Position 5

Phe
6

Phenylalanine

Position 6

Ser
7

Serine

Position 7

Cys
8

Cysteine

Position 8

Leu
9

Leucine

Position 9

Leu
10

Leucine

Position 10

Leu
11

Leucine

Position 11

Leu
12

Leucine

Position 12

Thr
13

Threonine

Position 13

Ser
14

Serine

Position 14

Glu
15

Glutamic Acid

Position 15

Ile
16

Isoleucine

Position 16

Asp
17

Aspartic Acid

Position 17

Leu
18

Leucine

Position 18

Pro
19

Proline

Position 19

Val
20

Valine

Position 20

Lys
21

Lysine

Position 21

Arg
22

Arginine

Position 22

Arg
23

Arginine

Position 23

Ala
24

Alanine

Position 24

N-terminus C-terminus
Hydrophobic
Polar
Positive (+)
Negative (-)
Modified
Peak 0.0 mcg
Trough 0.0 mcg
SS Peak 0.0 mcg
SS Trough 0.0 mcg

Research Indications

Neuroprotection
Alzheimer's Disease Protection effective

Originally discovered for its ability to protect against amyloid-β toxicity in neuronal cells.

Parkinson's Disease Support moderate

Promotes mitochondrial biogenesis via PI3K/AKT signaling in PD models.

General Neuroprotection effective

Broad neuroprotective effects against various neurotoxic insults.

Longevity
Lifespan Extension effective

Overexpression increases lifespan in C. elegans, dependent on daf-16/Foxo pathway.

Healthspan Improvement effective

HNG analog improves metabolic healthspan parameters in middle-aged mice.

Anti-Aging moderate

Higher levels associated with longevity in centenarians and their offspring.

Cellular Protection
Cytoprotection effective

Protects various cell types from stress-induced damage and death.

Anti-Apoptosis effective

Blocks pro-apoptotic proteins like Bax to prevent programmed cell death.

Mitochondrial Support effective

Promotes mitochondrial function and biogenesis.

Dosing Protocols

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.

GoalDoseFrequencyRoute
Neuroprotection1-5 mg2-3x weeklySubQ
Longevity/Anti-aging1-3 mg2x weeklySubQ
HNG analog0.5-2 mg2x weeklySubQ

Reconstitution Instructions

Materials Needed:
  • Bacteriostatic water (BAC)
  • Insulin syringes (0.5-1 mL)
  • Alcohol swabs
  • Peptide vial
  • Sterile work surface
  1. 1 Clean work area and hands thoroughly
  2. 2 Calculate required BAC water volume
  3. 3 Draw BAC water into syringe
  4. 4 Inject slowly down vial side (not directly onto powder)
  5. 5 Gently swirl until dissolved (never shake)
  6. 6 Store in refrigerator, protect from light

Interactions

++
MOTS-c
Both are mitochondria-derived peptides with complementary longevity and metabolic benefits.
synergistic
++
SS-31
Both target mitochondrial function; may have additive benefits for cellular health.
synergistic
+
Epitalon
Different mechanisms; can be combined in longevity protocols.
compatible
++
NAD+
Both support mitochondrial function and healthy aging.
synergistic

What to Expect

Week 1-2
Subtle; peptide begins working at cellular level
Week 2-4
Improved energy and reduced fatigue may begin
Week 4-8
Enhanced cellular resilience and stress response
Week 8-12
Cumulative benefits in mitochondrial function and healthspan markers
Long-term
Potential longevity and neuroprotective benefits

Side Effects & Safety

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

Quality Checklist

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

References

  • The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan
    Aging (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 Analogues
    Biology (MDPI) (2023)

    Comprehensive review of humanin's neuroprotective effects in Alzheimer's and Parkinson's disease models.

  • Mitochondria-derived peptides in aging and healthspan
    Journal of Clinical Investigation (2022)

    Review of mitochondria-derived peptides including humanin and their roles in aging and metabolic health.

  • Original Discovery of Humanin
    Proceedings 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.