Humanin
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Humanin

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A mitochondrial‑derived peptide first identified in neural tissues.

Key Research Properties:

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Lyophilized powder form
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$239.00
SKU: humanin
Purity: >99% (HPLC Verified)
Form: Lyophilized Powder
Storage: Store at -20°C
CAS Number: 330936-69-1
For Research Use Only.
All products are sold strictly for laboratory and research purposes. Products are not intended for human use or consumption of any kind.

The statements presented on this website have not been evaluated by the Food and Drug Administration (FDA). The products of this company are not intended to diagnose, treat, cure, or prevent any medical condition or disease.

What is Humanin?

Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) with potent cytoprotective, neuroprotective, and metabolic regulatory properties[1]. Discovered in 2001 in a screen for Alzheimer's disease-protective factors, Humanin has since been shown to protect against multiple age-related diseases, improve insulin sensitivity, and extend lifespan in animal models[2].

Cytoprotective Mitokine: Humanin is encoded in the mitochondrial genome and acts as a survival signal protecting cells from apoptosis, oxidative stress, and metabolic dysfunction. Its levels decline with age, and supplementation shows promise for age-related diseases including Alzheimer's, diabetes, and cardiovascular disease.
Biochemical Properties
  • Sequence: MAPRGFSCLLLLTSEIDLPVKRRA
  • Size: 24 amino acids (~2.7 kDa)
  • Origin: Encoded in mitochondrial 16S rRNA gene
  • Discovery: 2001 by Nishimoto et al. (Alzheimer's screen)
  • Classification: Mitochondrial-derived peptide (MDP)
  • Variants: HNG (highly potent analog with S14G mutation)
Primary Benefits
  • Neuroprotection: Protects against Alzheimer's, stroke, neurotoxicity
  • Metabolic Health: Improves insulin sensitivity; protects pancreatic β-cells
  • Cardiovascular: Protects heart from ischemia; reduces atherosclerosis
  • Anti-Apoptotic: Prevents programmed cell death in multiple tissues
  • Longevity: Extends lifespan in animal models; declines with age
  • Anti-Inflammatory: Reduces inflammatory signaling; modulates immune response

Molecular & Chemical Information

Peptide Sequence & Structure

Property Humanin
Peptide Sequence MAPRGFSCLLLLTSEIDLPVKRRA
Molecular Weight ~2,700 Da (2.7 kDa)
Length 24 amino acids
CAS Number 330936-69-1
Origin Mitochondrial 16S rRNA gene (MT-RNR2)
Receptor CNTFR/gp130/WSX-1 tripartite complex
Discovery Year 2001

Note: Humanin is a linear peptide encoded in the mitochondrial genome. The sequence represents the full-length 24-amino acid peptide with cytoprotective properties.

Key Research Findings

Breakthrough Discoveries

  • Age-Related Decline: Humanin levels decrease with aging; low levels associated with age-related diseases[3]
  • Alzheimer's Protection: Protects neurons from Aβ toxicity; reduces Alzheimer's pathology in models[2]
  • Insulin Sensitizer: Improves glucose metabolism; protects against diabetes[10]
  • Lifespan Extension: Transgenic mice overexpressing Humanin live longer, healthier lives[11]
  • Cardiovascular Protection: Reduces myocardial infarction damage; protects against atherosclerosis[15]
  • Receptor Identified: Binds to CNTFR/gp130/WSX-1 tripartite receptor complex[18]
Clinical Potential: Humanin's broad cytoprotective effects make it promising for multiple age-related diseases. Its decline with aging and restoration of function through supplementation suggest it could be a key longevity intervention.

Mechanism of Action

Humanin exerts cytoprotective effects through multiple mechanisms including anti-apoptotic signaling, metabolic regulation, and anti-inflammatory pathways[5].

Anti-Apoptotic Signaling

Cell Survival Pathways

Primary Mechanism: Humanin binds to the CNTFR/gp130/WSX-1 receptor complex, activating survival signaling cascades.

  • Receptor Binding: Tripartite receptor (CNTFR, gp130, WSX-1/IL-27Rα)
  • STAT3 Activation: Activates JAK-STAT3 pathway; promotes cell survival gene expression
  • PI3K/Akt: Activates PI3K/Akt pathway; phosphorylates and inactivates pro-apoptotic BAD
  • ERK1/2: Activates MAPK/ERK pathway; promotes cell survival and proliferation
  • Bcl-2 Family: Modulates Bcl-2/Bax ratio; prevents mitochondrial outer membrane permeabilization
  • Caspase Inhibition: Prevents caspase-3 and caspase-9 activation; blocks apoptosis execution

Neuroprotection

Alzheimer's & Neurodegeneration

  • Aβ Protection: Protects neurons from amyloid-beta toxicity (Alzheimer's)[2]
  • Oxidative Stress: Reduces ROS; enhances antioxidant defenses[13]
  • Mitochondrial Function: Preserves mitochondrial membrane potential; prevents dysfunction[4]
  • Inflammation: Reduces neuroinflammation; modulates microglial activation[12]
  • Synaptic Protection: Preserves synaptic function; improves cognitive performance[2]

Metabolic & Cardiovascular Protection

Insulin Sensitivity & Heart Protection

  • Insulin Sensitivity: Improves glucose uptake; enhances insulin signaling[10]
  • β-Cell Protection: Protects pancreatic β-cells from apoptosis; preserves insulin secretion[10]
  • Lipid Metabolism: Improves lipid profiles; reduces ectopic fat accumulation[10]
  • Cardioprotection: Protects cardiomyocytes from ischemia-reperfusion injury[9]
  • Atherosclerosis: Reduces plaque formation; stabilizes existing plaques[17]
  • Endothelial Function: Improves vascular function; reduces endothelial dysfunction[14]
Mechanism Summary: Humanin acts as a broad-spectrum cytoprotective agent through anti-apoptotic signaling, metabolic optimization, and anti-inflammatory effects. Its multi-target approach makes it effective against diverse age-related pathologies.

Research & Evidence

Humanin has been extensively studied for Alzheimer's disease, metabolic disorders, cardiovascular disease, and aging, with consistent cytoprotective effects across models[3].

Alzheimer's & Neurodegeneration

Neuroprotective Research

Key Findings: Humanin protects against Aβ toxicity and improves cognitive function in Alzheimer's models.

  • Aβ Toxicity: Protects neurons from amyloid-beta-induced death in vitro and in vivo[2]
  • Cognitive Function: Improves memory and learning in Alzheimer's disease models[2]
  • Brain Pathology: Reduces amyloid plaques and neurofibrillary tangles[7]
  • Clinical Correlation: Low Humanin levels in Alzheimer's patients; inverse correlation with disease severity[1]
  • Stroke Protection: Reduces infarct size and neurological deficits in stroke models[6]

Metabolic & Cardiovascular Research

Diabetes & Heart Disease

  • Insulin Resistance: Improves glucose tolerance and insulin sensitivity in diabetic models[10]
  • Type 2 Diabetes: Low Humanin levels in diabetic patients; supplementation improves metabolic parameters[10]
  • Myocardial Infarction: Reduces heart damage and improves recovery after heart attack[9]
  • Atherosclerosis: Reduces plaque formation; stabilizes vulnerable plaques[17]
  • Heart Failure: Protects against heart failure progression in animal models[15]

Aging & Longevity

Lifespan & Healthspan

  • Age-Related Decline: Humanin levels decrease with age in humans and animals[3]
  • Lifespan Extension: Transgenic mice overexpressing Humanin live significantly longer[11]
  • Healthspan: Improved physical function, metabolic health in aged animals[11]
  • Centenarian Studies: Higher Humanin levels in centenarians vs. age-matched controls[11]
  • Age-Related Diseases: Protective against multiple age-related pathologies[8]
Research Status: Humanin has extensive preclinical data. Human studies show correlations between Humanin levels and disease states. Clinical trials for therapeutic applications are needed.

Dosing & Administration

Research Use Only: Humanin is for research purposes. No FDA approval for clinical use.

Research Dosing (Extrapolated from Animal Studies)

Subcutaneous/Intramuscular Administration

Community/Anecdotal Doses: Based on animal study extrapolation

  • Conservative Dose: 1-2 mg SC/IM, 2-3× weekly
  • Standard Dose: 2-5 mg SC/IM, 2-3× weekly
  • Higher Dose: 5-10 mg SC/IM, 2-3× weekly (some reports)
  • HNG (Potent Analog): 0.5-2 mg SC/IM, 2-3× weekly (more potent than standard Humanin)
  • Timing: No specific timing requirements; consistent schedule recommended
  • Duration: Cycles of 4-12 weeks; breaks between cycles
Note: Animal studies used 2-4 mg/kg IP/IV. Human equivalent doses would be much lower. Community doses require clinical validation.

Reconstitution & Storage

  • Lyophilized Powder: Store at -20°C until reconstitution
  • Reconstitution: Bacteriostatic water for injection
  • Reconstituted Storage: Refrigerate at 2-8°C; use within 7 days
  • Handling: Gently swirl; avoid vigorous shaking

Safety & Side Effects

Humanin has demonstrated excellent safety in animal studies with no significant adverse effects at therapeutic doses[11].

Preclinical Safety Profile

Animal Studies: Humanin shows excellent tolerability across multiple species.

  • No Toxicity: No significant adverse effects in preclinical studies
  • Long-Term Safety: Chronic administration well-tolerated in animals
  • Organ Function: No adverse effects on liver, kidney, heart function
  • Natural Peptide: Endogenously produced; supplementation mimics physiological levels
  • Overexpression: Transgenic mice with lifelong Humanin overexpression show no adverse effects
Human Safety: Limited human data. Observational studies show Humanin levels vary naturally without apparent harm. Therapeutic supplementation safety requires clinical trial validation.

Frequently Asked Questions

Humanin is a mitochondrial-derived peptide discovered in 2001 during Alzheimer's research. It's a survival signal that protects cells from death, stress, and dysfunction. Its levels decline with age, and low levels are associated with Alzheimer's, diabetes, and cardiovascular disease. Restoring Humanin may combat multiple age-related diseases simultaneously.

Primary research areas: Alzheimer's disease (neuroprotection from Aβ), Type 2 diabetes (insulin sensitivity, β-cell protection), cardiovascular disease (myocardial infarction, atherosclerosis), stroke (neuroprotection), and aging/longevity (lifespan extension in animal models).

HNG (Humanin with S14G mutation) is a highly potent analog of Humanin that's 1000× more effective in some assays. The single amino acid substitution (serine to glycine at position 14) dramatically increases potency. HNG is often preferred for research due to its enhanced activity, allowing lower doses.

In animal studies, cytoprotective effects are rapid (hours to days). Metabolic improvements appear within 1-2 weeks. Neuroprotective and longevity effects require longer-term administration (weeks to months). Human response times are not well-characterized and likely vary by condition and individual.

No. Humanin is not FDA-approved. It remains in preclinical and early clinical research. Available for research purposes only. Given its broad cytoprotective effects and excellent safety profile in animals, clinical trials are warranted.

Clinical Trials & Development Status

Humanin has extensive preclinical research and emerging human observational data. Several clinical trials are currently investigating Humanin's role in acute kidney injury and cardiovascular complications.

Research Note: Humanin research spans multiple disease areas including neurodegenerative diseases, metabolic disorders, cardiovascular conditions, and acute organ injury. The clinical trials below focus on acute kidney injury and cardiac surgery complications, reflecting Humanin's cytoprotective properties.

Registered Clinical Trials

NCT06105229: Clinical Value of Plasma Humanin in Acute Kidney Injury

Official Title: Clinical Value of Plasma Humanin in Acute Kidney Injury

Status: Unknown status

Condition: Acute Kidney Injury

Location: Guangdong, Guangzhou, China

ClinicalTrials.gov Identifier: NCT06105229

Study Focus: This trial investigates the clinical value of plasma Humanin levels in patients with acute kidney injury, exploring its potential as a biomarker and therapeutic target.

NCT06125249: Humanin's Value for Early Diagnosis and Short-term Prognosis in Patients With AKI After Heart Transplantation

Official Title: Humanin's Value for Early Diagnosis and Short-term Prognosis in Patients With AKI After Heart Transplantation

Status: Recruiting

Conditions:

  • Acute Kidney Injury
  • Heart Transplant Surgery

Location: Guangdong, Guangzhou, China

ClinicalTrials.gov Identifier: NCT06125249

Study Focus: This actively recruiting trial evaluates Humanin's potential as a biomarker for early diagnosis and prognosis prediction in patients who develop acute kidney injury following heart transplantation. The study aims to assess whether Humanin levels can help identify patients at risk and predict short-term outcomes.

NCT03431844: Humanin Isoforms in Cardiac Muscle and Blood Plasma and Major Complications After Cardiac Operation

Official Title: Humanin Isoforms in Cardiac Muscle and Blood Plasma and Major Complications After Cardiac Operation

Status: Completed

Conditions:

  • Coronary Artery Bypass Surgery
  • Myocardial Ischemia

Locations:

  • Tallinn, Harju, Estonia
  • Tartu, Tartu, Estonia

ClinicalTrials.gov Identifier: NCT03431844

Study Focus: This completed trial investigated Humanin isoforms in cardiac muscle tissue and blood plasma in relation to major complications following cardiac operations. The study examined the relationship between Humanin expression patterns and post-operative outcomes in patients undergoing coronary artery bypass surgery.

Preclinical Research

Animal Model Studies

Extensive Preclinical Foundation: Humanin has been studied in multiple disease models with consistent cytoprotective effects.

  • Alzheimer's Models: Protects against Aβ toxicity; improves cognition in APP/PS1 mice
  • Diabetes Models: Improves glucose tolerance and insulin sensitivity in db/db, high-fat diet models
  • Cardiovascular Models: Reduces infarct size in MI models; protects against atherosclerosis
  • Aging/Longevity: Transgenic overexpression extends lifespan and healthspan
  • Safety: No adverse effects in chronic dosing studies

Human Observational Studies

Clinical Correlations

Human Studies: Observational research links Humanin levels to disease and longevity.

  • Alzheimer's Disease: Lower Humanin levels in AD patients vs. controls; inverse correlation with disease severity
  • Type 2 Diabetes: Reduced Humanin in diabetic patients; correlation with insulin resistance
  • Cardiovascular Disease: Lower levels in patients with atherosclerosis, heart failure
  • Aging: Humanin declines with age in general population
  • Longevity: Higher Humanin levels in centenarians vs. age-matched controls

Implication: These correlations support Humanin's role in disease protection and suggest therapeutic potential.

Find More Studies: Search PubMed: Humanin Research | ClinicalTrials.gov
Research Summary: Humanin has compelling preclinical efficacy across multiple age-related diseases and excellent safety. Human observational data support its protective role. Clinical trials are actively investigating its role in acute kidney injury and cardiovascular complications, building on the strong preclinical foundation.

References & Scientific Citations

Research Integrity:

All references are from peer-reviewed journals documenting Humanin discovery and research. All claims made on this page are backed by published scientific literature.

Citations

  1. Matsuoka M, Hashimoto Y. Humanin and the receptors for humanin. Mol Neurobiol. 2010;41(1):22-28. [Springer]
  2. Nishimoto I, Matsuoka M, Niikura T. Unravelling the role of Humanin. Trends Mol Med. 2004;10(3):102-105. [Cell Press]
  3. Coradduzza D, Congiargiu A, Chen Z, Cruciani S. Humanin and its pathophysiological roles in aging: A systematic review. Biology (Basel). 2023;12(4):558. [MDPI]
  4. Lee C, Yen K, Cohen P. Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol Metab. 2013;24(5):222-228. [Cell Press]
  5. Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, et al. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003;423(6938):456-461. [Nature]
  6. Xu X, Chua CC, Gao J, Hamdy RC, Chua BHL. Humanin is a novel neuroprotective agent against stroke. Stroke. 2006;37(10):2613-2619. [AHA Journals]
  7. Niikura T, Chiba T, Aiso S, Matsuoka M. Humanin: after the discovery. Mol Neurobiol. 2004;30(3):327-340. [Springer]
  8. Gong Z, Tas E, Muzumdar R. Humanin and age-related diseases: a new link? Front Endocrinol (Lausanne). 2014;5:210. [Frontiers]
  9. Charununtakorn ST. Potential roles of humanin on apoptosis in the heart. Cardiovasc Hematol Disord Drug Targets. 2016;16(1):45-52. [Wiley Online Library]
  10. Muzumdar RH, Huffman DM, Atzmon G, Buettner C, et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One. 2009;4(7):e6334. [PLOS ONE]
  11. Yen K, Mehta HH, Kim SJ, Lue YH, Hoang J. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY). 2020;12(12):11185-11199. [PMC]
  12. Karachaliou CE, Livaniou E. Neuroprotective action of humanin and humanin analogues: research findings and perspectives. Biology (Basel). 2023;12(12):1534. [MDPI]
  13. Yen K, Lee C, Mehta H. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013;50(1):R11-R19. [PMC]
  14. Widmer RJ, Flammer AJ, Herrmann J, et al. Circulating humanin levels are associated with preserved coronary endothelial function. Am J Physiol Heart Circ Physiol. 2013;304(3):H393-H398. [American Journal of Physiology]
  15. Rochette L, Meloux A, Zeller M, Cottin Y. Role of humanin, a mitochondrial-derived peptide, in cardiovascular disorders. Arch Cardiovasc Dis. 2020;113(8-9):564-571. [ScienceDirect]
  16. Bodzioch M, Lapicka-Bodzioch K, Zapala B, Kamysz W. Evidence for potential functionality of nuclearly-encoded humanin isoforms. Genomics. 2009;93(3):247-256. [ScienceDirect]
  17. Bachar AR, Scheffer L, Schroeder AS, et al. Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress. Cardiovasc Res. 2010;88(2):360-366. [Oxford Academic]
  18. Ying G, Iribarren P, Zhou Y. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol. 2004;172(11):7078-7085. [ResearchGate]
  19. Thamarai Kannan H, Issac PK, Dey N, Guru A. A review on mitochondrial derived peptide humanin and small humanin-like peptides and their therapeutic strategies. Int J Pept Res Ther. 2023;29(4):58. [Springer]
  20. Lei H, Rao M. The role of humanin in the regulation of reproduction. Biochim Biophys Acta Gen Subj. 2022;1866(1):130018. [ScienceDirect]

Additional Resources

For researchers interested in further reading:

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Not for human consumption, medical, or veterinary use.

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