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LONGEVITYPEPTIDE PROFILE

Humanin

Also known as HN, HNG, Mitochondrial Derived Peptide, MDP, MOTS-c family

Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of the mitochondrial genome. First identified in 2001 from brain tissue of an Alzheimer's patient, humanin is an endogenous cytoprotective factor whose levels decline with age. In cell and animal models it protects neurons from amyloid-beta toxicity, improves insulin sensitivity, reduces inflammation, and extends healthspan. All of that evidence is preclinical: no human has been given humanin in a published clinical trial.

Last updated April 10, 2026

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Humanin: quick citable summary

Humanin is listed by PeptaHub as a longevity peptide with a research only legal-status classification. The page summarizes mechanism, research context, common routes, safety notes, and references for writers and AI answer engines.

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PeptaHub. “Humanin: Mechanism, Research Context, Safety.” peptahub.com, 2026. https://peptahub.com/peptides/humanin. Licensed CC BY 4.0.

License: Creative Commons Attribution 4.0 International. Link back to https://peptahub.com/peptides/humanin.

SAMEAS / EXTERNAL IDS
Humanin CAS: 330936-69-1
QUICK ANSWER

What is Humanin?

Humanin is a 24-amino acid mitochondrial-derived peptide whose levels decline with age. In animal models it protects neurons from amyloid-beta toxicity, improves insulin sensitivity, and extends healthspan. There is no human clinical trial data, so all dosing is extrapolated from mouse studies.

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Overview

Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of the mitochondrial genome. First identified in 2001 from brain tissue of an Alzheimer's patient, humanin is an endogenous cytoprotective factor whose levels decline with age. In cell and animal models it protects neurons from amyloid-beta toxicity, improves insulin sensitivity, reduces inflammation, and extends healthspan. All of that evidence is preclinical: no human has been given humanin in a published clinical trial.

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Mechanism of action

Humanin acts through two main receptor systems. Extracellularly, it signals via a heterotrimeric receptor complex comprising ciliary neurotrophic factor receptor alpha (CNTFRα), WSX-1, and gp130, activating JAK2/STAT3 and PI3K/Akt pro-survival pathways. Intracellularly, humanin directly binds and inhibits pro-apoptotic Bax protein, preventing mitochondrial outer membrane permeabilization and cytochrome c release. In neuronal contexts, humanin blocks amyloid-beta (Aβ) oligomer-induced apoptosis by inhibiting Aβ binding to cell surface receptors and downstream caspase activation. It also suppresses inflammatory NF-κB signaling, improves mitochondrial membrane potential, and enhances autophagy to clear damaged organelles. Humanin levels in plasma and CSF correlate inversely with Alzheimer's disease severity.

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Reported study ranges

PurposeRouteReported rangeFrequency
Neuroprotection / metabolic healthspan (preclinical protocol)subcutaneous2.55 mg/kgtwice weekly

Reported ranges are for research context only. Consult a qualified healthcare professional before using any peptide.

Convert Humanin research-range units

Need to convert mg to mcg, dose volume, or U-100 syringe units? Use the peptide dose unit converter for educational calculation support.

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Research summary

The central study is Yen et al. (Aging, 2020). In it, overexpressing humanin extended lifespan in C. elegans in a daf-16/FOXO-dependent way — that is a genetic manipulation in worms, not administration of the peptide. Treating middle-aged mice twice weekly with the analogue HNG improved metabolic healthspan parameters and reduced inflammatory markers. The same paper reports that humanin levels generally decline with age across species, that they are decreased in Alzheimer's disease and MELAS, and that children of centenarians have markedly higher circulating humanin than age-matched controls. That last finding is an association in a selected group, not evidence that raising humanin improves cognitive aging. No human clinical trial of exogenous humanin has been completed or registered as of 2026.[1][2][3][4][5]

📄This section cites 5 peer-reviewed sources. View all references →
§ 04b

Evidence grading

Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.

preliminary
Neuroprotection vs amyloid-beta toxicityThiankhaw et al. BBA Gen Subj 2022 and Karachaliou & Livaniou Biology 2023 reviews of rodent and cell-model data; no human neurodegenerative trials
preliminary
Metabolic healthspan and insulin sensitivityYen et al. Aging 2020: HNG twice weekly in middle-aged mice improved metabolic healthspan parameters and lowered inflammatory markers; preclinical only
moderate
Bax-mediated anti-apoptotic activityMultiple biochemical studies confirm direct Bax binding and mitochondrial protection; mechanism well-characterized in vitro
preliminary
Cardioprotection from ischemia-reperfusionGong, Goetzman & Muzumdar BBA Gen Subj 2022: review of preclinical myocardial ischemia-reperfusion work; no human cardiac data
insufficient
Human anti-aging or cognitive efficacyNo human clinical trials of exogenous humanin completed or registered as of 2026; all dosing extrapolated from animal data

Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data

§ 05

Side effects

Unknown in humans — no human safety data exists
Injection site reactions
Theoretical hypoglycemia risk given insulin-sensitizing effects
Unknown long-term effects

Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.

§ 06

Common stacks

Peptides commonly paired with Humanin for synergistic effects.

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Sourcing & access

Research compound

Humanin is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).

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Frequently asked questions

Humanin is a 24-amino acid peptide encoded within the 16S ribosomal RNA gene of the mitochondrial genome. First identified in 2001 from brain tissue of an Alzheimer's patient, it is an endogenous cytoprotective factor that declines with age and has broad implications for aging and neurodegeneration.

Humanin signals extracellularly via a CNTFRalpha/WSX-1/gp130 receptor complex, activating JAK2/STAT3 and PI3K/Akt survival pathways. Intracellularly, it directly binds and inhibits pro-apoptotic Bax protein. It blocks amyloid-beta-induced apoptosis and suppresses NF-kB inflammatory signaling.

No human safety data exists since no human clinical trials have been completed. Theoretical risks include hypoglycemia from insulin-sensitizing effects. Known side effects from research contexts are limited to injection site reactions.

Humanin levels are reduced in people with Alzheimer's disease, and children of centenarians carry markedly higher circulating humanin than age-matched controls (Yen et al., Aging 2020). Both are associations — no study has shown that raising humanin changes the course of the disease. Neuroprotective effects against amyloid-beta come from cell and rodent models, and no human trial has been run.

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Research references

  1. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspanYen K, Mehta HH, Kim SJ, et al.Aging (Albany NY), 2020PubMed
  2. Humanin and Its Pathophysiological Roles in Aging: A Systematic ReviewCoradduzza D, Congiargiu A, Chen Z, et al.Biology (Basel), 2023Review
  3. Roles of humanin and derivatives on the pathology of neurodegenerative diseases and cognitionThiankhaw K, Chattipakorn K, Chattipakorn SC, et al.Biochimica et Biophysica Acta - General Subjects, 2022PubMed
  4. Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and PerspectivesKarachaliou CE, Livaniou EBiology (Basel), 2023PubMed
  5. Cardio-protective role of Humanin in myocardial ischemia-reperfusionGong Z, Goetzman E, Muzumdar RHBiochimica et Biophysica Acta - General Subjects, 2022PubMed
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