Side-by-side · Research reference

HumaninvsLivagen

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED14/52 cited

BAnimal-StrongHUMAN-REVIEWED20/32 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Livagen

Khavinson Bioregulator · Hepatoprotective Tetrapeptide

50%Dipeptidase inhibitionTimofeeva 2005

Oral / SQRoutes tested

LiverTarget tissueKhavinson 2001

Oral or SQ · Tissue-specific to liver

01Mechanism of Action

Parameter

Humanin

Livagen

Primary target

Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022 Lue 2021

Hepatocyte protein synthesis machineryBrodskiĭ 2001

Pathway

Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival

Tissue-specific bioregulator → Hepatocyte stimulation → Protein synthesis normalizationBrodskiĭ 2001 Khavinson 2001

Downstream effect

Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022 Lue 2021 Velentza 2024

Age-dependent enzyme normalization, hepatoprotection in fibrosis/hepatitis models, elevated protein synthesis in senescent hepatocytes

Feedback intact?

Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis

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Origin

Encoded by short open reading frame in mitochondrial 16S rRNA gene (MTRNR2). 24-28 amino acids. 13 homologous variants (MTRNR2L1-L13) identified.Zhu 2022 Shahzaib 2026

Directed chemical synthesis from amino acid analysis of liver polypeptide preparations (Ventvil)

Antibody development

Not reported in animal models

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02Dosage Protocols

Parameter

Humanin

Livagen

Standard experimental dose (HNG)

4 mg/kg IP (rat)

Most common dose in rodent models.

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Ex vivo bone culture

1 µg/mL

Protective against venetoclax-induced bone growth retardation.

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Frequency

Daily (IP)

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Duration

8–12 weeks in animal studies

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Evidence basis

Animal models (rat, mouse)Huang 2025 El 2022 Velentza 2024

Animal models (rats, 1–24 months age); in vitro hepatocyte cultureTimofeeva 2005 Brodskiĭ 2001 Khavinson 2002

Human data

None — no clinical trials reported

None in provided literature

Analog (HNG)

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

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Animal dose (oral)

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Not specified in abstracts; 2-week administration protocolTimofeeva 2005

Per os administration in rats.

Duration (experimental)

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2 weeks (enzyme study); up to 24 months (cell culture)Timofeeva 2005 Brodskiĭ 2001

Route

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Oral or subcutaneous

Resists peptidase hydrolysis, enabling oral bioavailability.Timofeeva 2005

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Livagen

Direct fat loss evidence

None

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Mechanism overlap

Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect

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04Side Effects & Safety

Parameter

Humanin

Livagen

Animal model safety

Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks

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Human safety data

None — no clinical trials

No human trials in provided literature

Theoretical fibrillation risk

Induces amyloid-like fibrillation of Bax/BID. Long-term sequelae unknown.

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Injection site reaction

Not reported in animal studies (IP route)

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Reproductive safety

Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025

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Reported adverse effects

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None documented in animal studies

Peptide hydrolysis

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Weakly hydrolyzed; minimal breakdown by intestinal enzymesTimofeeva 2005

Absolute Contraindications

Humanin

·Unknown — no human data

Livagen

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Relative Contraindications

Humanin

·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)

Livagen

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05Administration Protocol

Parameter

Humanin

Livagen

1. Route (experimental)

Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.

Oral administration supported by peptidase resistance. Subcutaneous route used in organotypic culture experiments.Timofeeva 2005 Khavinson 2001

2. Reconstitution

Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.

No specific timing documented. Two-week protocols used in animal models with daily administration.Timofeeva 2005

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

Elderly individuals may exhibit different enzyme normalization patterns than younger cohorts, based on rat age-stratified findings.Timofeeva 2005

4. Storage

Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.

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5. Human use

No FDA approval, no IND, no clinical trials. Experimental research tool only.

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06Stack Synergy

Humanin

+ MOTS-c

Multi-pathway

View MOTS-c →

Both are mitochondrial-derived peptides. MOTS-c enhances metabolic efficiency and insulin sensitivity via AMPK activation, while humanin prevents mitochondrial apoptosis. Combined, they address mitochondrial function (MOTS-c) and survival signaling (humanin), supporting cellular resilience under metabolic and oxidative stress.

Humanin: 4 mg/kg IP · daily (animal model)
MOTS-c: 5 mg/kg IP · daily (animal model)
Frequency: Once daily
Primary benefit: Mitochondrial health, metabolic efficiency, anti-apoptotic signaling

Livagen

— no documented stacks