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ID: HUMANIN STATUS: ACTIVE

Humanin

Research Only

Also known as: HN, HNG, S14G-Humanin, HN peptide, Colivelin

A 24-amino acid mitochondria-derived peptide (MDP) discovered in 2001 that shows cytoprotective, anti-apoptotic, and neuroprotective effects in preclinical studies. Represents a novel class of signaling molecules encoded within mitochondrial DNA. Extensive academic research with emerging interest in aging, metabolic disease, and neurodegeneration, but no approved clinical applications.

Longevity Moderate Evidence 50 Sources

Research Statistics

Total Sources
50
Human Studies
10
Preclinical
40
Evidence Rating Low Evidence
Research Depth 3/5
Global Coverage 2/5
Mechanism Plausibility 3/5
Overall Score
2.5 /5

Emerging mitochondrial peptide with growing international interest; FPRL2/GP78 signaling mechanism proposed with some supporting data but predominantly preclinical.

Last reviewed February 2026 How we rate →
~
Evidence Level
moderate
Not approved for human use by any regulatory agency
Limited human clinical trial data
Consult a healthcare provider before use
Not FDA Approved WADA Prohibited

Research Dossier

01 / 7

Overview

What is Humanin and what does the research say?

Identity
Also Known As
HN • HNG • S14G-Humanin • HN peptide • Colivelin
Type
Mitochondria-Derived Peptide (MDP)
Length
24 amino acids
Weight
2,687.17 Da
Sequence
MAPRGFSCLLLLTSEIDLPVKRRA
Molecular Structure
M
A
P
R
G
F
S
C
L
L
L
L
T
S
E
I
D
L
P
V
K
R
R
A
Hydrophobic
Polar
Positive
Negative

Mechanism of Action

Humanin is a mitochondria-derived peptide (MDP) discovered in 2001 through its ability to rescue cells from Alzheimer’s-related death. It represents a novel class of signaling molecules encoded within mitochondrial DNA.

How It Works (Simplified)

Humanin protects cells through multiple complementary mechanisms:

1
Receptor Signaling

Binds FPRL1/2 receptors, activating ERK1/2 and STAT3 pathways that promote cell survival and inhibit apoptosis.

2
BAX Binding

Directly binds pro-apoptotic BAX protein, preventing mitochondrial permeabilization and blocking the death cascade.

3
Mitochondrial Support

Improves mitochondrial function, reduces oxidative stress, and prevents cytochrome c release from damaged mitochondria.

4
IGF Modulation

Binds IGFBP-3 to modulate insulin-like growth factor signaling, with implications for metabolism and aging.

Scientific Pathways

FPRL Receptor Signaling (Anti-Apoptotic)

Humanin → FPRL1/2 receptor → Gαi/o coupling → ERK1/2 activation

                                              STAT3 signaling

                                       Anti-apoptotic gene expression

BAX Inhibition Pathway (Cytoprotection)

Humanin → Direct BAX binding → Blocks BAX oligomerization

                          Prevents mitochondrial permeabilization

                        Inhibits cytochrome c release → Cell survival

Key Research: Hashimoto Y et al. (2001) discovered humanin through functional screening for factors that rescue cells from FAD gene toxicity. PMID:11408622

Important Limitations

  • No therapeutic trials — Despite 20+ years of research, no human treatment studies
  • Complex biology — Multiple mechanisms complicate drug development
  • Cancer question — Anti-apoptotic effects could theoretically promote tumor survival
  • Delivery challengesPeptide stability and pharmacokinetics not optimized
  • All human data correlativeBiomarker studies, not cause-and-effect

Evidence-Chained Benefits

Evidence-Chained Benefits

Research findings linked to mechanisms and clinical outcomes

Mechanism FPRL1/2 receptor binding activating ERK1/2 and STAT3 anti-apoptotic signaling
Established 15 direct studies
Benefit shown to protect cells from apoptotic death
Evidence Level
Moderate
20 Animal
25 In Vitro
Mechanism Direct BAX and Bid binding blocking mitochondrial apoptosis cascade
Established 8 direct studies
Benefit appears to provide neuroprotection in disease models
Evidence Level
Moderate
15 Animal
12 In Vitro
Mechanism Improved mitochondrial function and reduced oxidative stress
Supported 10 direct studies
Benefit may improve metabolic function
Evidence Level
Low
5 Human
12 Animal
8 In Vitro
Mechanism IGFBP-3 binding modulating IGF signaling pathway
Supported 6 direct studies
Benefit suggested to modulate aging-related signaling pathways
Evidence Level
Low
8 Human
6 Animal
5 In Vitro
Mechanism Confidence
Established
Supported
Emerging
Evidence Level
High
Moderate
Low
Very Low

What to Expect

Timeline based on observations from published studies. Individual responses may vary.

Humanin binds FPRL receptors rapidly, activating ERK1/2 and STAT3 signaling within minutes. Anti-apoptotic effects are immediate in cellular models. In vivo distribution and kinetics not fully characterized.

Days to weeks PMID:15655255

Preclinical studies typically administer humanin or HNG for days to weeks. Neuroprotective effects in AD models observed over weeks of treatment. Metabolic improvements in diabetic mice seen within weeks.

Long-term PMID:26221185

Endogenous humanin levels decline with age (from higher levels in youth to lower in elderly). Long-term effects of exogenous supplementation are not characterized. No human chronic administration data available.

Research-Based Observations

This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.

Quality Checklist

Visual indicators to help evaluate Humanin product quality

Good Signs (6 indicators)
White to off-white lyophilized powder
Complete dissolution in appropriate solvent
Certificate of analysis showing >95% purity
HPLC verification of identity
Mass spectrometry confirmation
Proper vacuum seal on vial
Warning Signs (5 indicators)
Slightly off-white coloration
Slow dissolution time
No third-party testing verification
Purity below 95%
Limited supplier documentation
Bad Signs (5 indicators)
Discolored powder (yellow, brown)
Particles or cloudiness after dissolution
No certificate of analysis
Cannot verify source or identity
Compromised vial seal
Positive quality indicator
Requires evaluation
Potential quality issue

For Research Evaluation Only

These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.

Peptide Interactions

Known and theoretical interactions when combining Humanin with other peptides. Based on published research and mechanistic considerations.

Synergistic
Compatible
Caution
Avoid

Both are mitochondria-derived peptides with complementary mechanisms. Humanin is cytoprotective while MOTS-c is metabolic. May provide synergistic longevity benefits through different pathways.

Ss-31

Compatible
Compatible

Both target mitochondrial function. SS-31 acts on cardiolipin while humanin signals through FPRL receptors. Non-overlapping mechanisms with potential complementary benefits.

Different anti-aging mechanisms - humanin provides cytoprotection while epithalon targets telomerase. No known interactions.

Different protective mechanisms - humanin acts on apoptosis pathways while BPC-157 promotes angiogenesis and tissue repair.

Both have neuroprotective properties through different mechanisms. Humanin inhibits apoptosis while cerebrolysin provides neurotrophic factors.

Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.

References

Methodology Note

This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.

For complete methodology details, see our Methodology page.

Important Disclaimer

This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.

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