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Humanin

From PeptidePlaza, the free peptide reference · Entry #018 · Anti-Aging · Hand-curated entry · Editorial standards

Research warning. For educational reference only. Native Humanin has extremely short half-life. HNG (Gly14) variant is more stable for research use. No human trials for any indication.

Humanin (also known as HN, Humanin G (HNG — Gly14 variant)) is a anti-aging research peptide. A 21-amino acid mitochondria-encoded peptide discovered through its ability to rescue neurons from Alzheimer's-related death. Like MOTS-c, it belongs to the emerging class of mitochondrial-derived peptides with systemic metabolic and cytoprotective effects.

Humanin is a 21-amino acid peptide encoded in the 16S rRNA region of the mitochondrial genome, discovered in 2001 by Nishimoto et al. while screening for factors that rescue neurons from Alzheimer's disease-related apoptosis. It acts via multiple receptors (FPRL1, gp130/CNTFR/WSX-1 tripartite receptor complex) to exert cytoprotective, anti-apoptotic, and metabolic effects. Circulating Humanin levels decline significantly with age. Research links it to improved insulin sensitivity (via STAT3), neuroprotection, sperm protection against apoptosis, cardiovascular protection, and life extension in animal models.

1 Mechanism of action

Binds FPRL1 and the gp130/CNTFR/WSX-1 receptor complex. Activates STAT3 and PI3K/Akt survival pathways. Inhibits BAX-mediated apoptosis. Reduces mitochondrial ROS. Improves peripheral insulin sensitivity via hypothalamic STAT3 signaling.

Primary targets: FPRL1 · gp130/CNTFR/WSX-1 complex · STAT3 pathway

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • Neuroprotection against Alzheimer's-related amyloid toxicity
  • Improved insulin sensitivity via STAT3 pathway
  • Anti-apoptotic effects across multiple tissue types

2.2 Side effects

  • Rapid degradation (native form) — limited bioavailability
  • Injection site reactions
  • Long-term human side-effect profile unknown

3 Chemical and physical properties

CAS number330936-69-1
Molar mass2887.36 g/mol
Purity (typical)>98.0%
Half-life~minutes (native); HNG variant more stable
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsFPRL1, gp130/CNTFR/WSX-1 complex, STAT3 pathway

3.1 Amino acid sequence

MAPRGFSCLLLLTSEIDLPVKRRA

4 Research dosages

2–5 mg/kg SC in rodent models; human-equivalent dose not established.

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (8)

  1. Humanin: A Peptide Encoded by Mitochondrial DNA Protects Neurons from Alzheimer's Disease
    Nature Cell Biology (2001) · Preclinical · N=120 (cell cultures)
    Discovery paper. Humanin rescued neurons from Aβ- and mutant APP-induced apoptosis; identified as a mitochondrially encoded neuroprotective factor.
    Key finding: Humanin rescue of Aβ42-induced neuronal death established a new class — mitochondrial-derived cytoprotective peptides.
  2. Circulating Humanin Levels Are Associated with Aging and Metabolic Disease
    Aging Cell (2013) · Observational · N=362 (human)
    Humanin levels inversely correlate with age and insulin resistance in humans; HNG treatment improved metabolic parameters in diabetic mice.
    Key finding: Humanin levels decline 30–50% from ages 20–70; low levels independently predict insulin resistance and metabolic syndrome.
  3. Network Topology and Interactomic Analysis Reveal the Regulatory Framework of the Humanin Protein Family (MTRNR2Lx Class)
    Biomolecules (2026) · Preclinical
    Humanin biology and identify prioritized molecular candidates for future in vitro and in vivo validation in the context of neurodegeneration, apoptosis, and cellular stress.
  4. S14G-humanin (HNG) ameliorates diabetic nephropathy tubular injury by inhibiting Z-DNA/ZBP1-mediated necroptosis
    European journal of pharmacology (2026) · Preclinical
    HNG ameliorates DN tubular injury by inhibiting BAX-driven mitochondrial oxidative stress and subsequent Z-DNA/ZBP1-mediated necroptosis, highlighting HNG as a promising therapeutic candidate for DN.
  5. Humanin peptide ameliorates reproductive dysfunction and restores neuroendocrine mechanisms in SSRI-treated male rats
    Reproductive biology (2026) · RCT
    By preserving mitochondrial integrity and modulating central dopaminergic and neuroendocrine circuits, humanin emerges as a promising therapeutic agent for preserving male reproductive health during SSRI treatment.
  6. Neuroprotective effect of intraperitoneal Humanin-G in retinal degeneration of Royal College of Surgeons rats
    Scientific reports (2026) · Preclinical
    PMID: 42471450 Competing interests: The authors declare no competing interests.
  7. Altered placental expression of small humanin-like peptides in gestational diabetes mellitus
    Upsala journal of medical sciences (2026) · Preclinical
    This study demonstrates that placental mRNA levels of SHLPs are reduced in pregnancies complicated by GDM and are associated with maternal metabolic status.
  8. Repeated Humanin Treatment Attenuates Oxidative Stress, Inflammation, and Apoptosis in Diabetic Cardiac Tissue
    Biology (2026) · Preclinical
    The results further suggest that HN may represent a promising therapeutic candidate for limiting diabetes-associated cardiac complications.

6 Safety and risk profile

6.1 Regulatory status

Humanin is currently classified as Investigational. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.

Safety score: 30/100 — high concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • Unknown — insufficient human safety data
  • Pregnancy (no reproductive toxicity data)
  • Active B-cell malignancies (STAT3 pathway concern)

6.3 Drug interactions

Drug or classInteractionRisk
JAK/STAT inhibitors (ruxolitinib, tofacitinib)Humanin signals via STAT3 — JAK inhibitors may block its metabolic effects.Moderate
BAX inhibitors / pro-apoptotic chemotherapiesHumanin inhibits BAX-mediated apoptosis — may interfere with pro-apoptotic cancer therapies.High

6.4 Long-term risks

  • BAX inhibition may impair tumor surveillance
  • Unknown long-term effects of STAT3 pathway activation
  • No chronic toxicity data available

6.5 Research best practices

  • Store at −20 °C; protect from light
  • Use HNG (S14G) variant for improved stability in protocols
  • Reconstitute immediately before use due to rapid degradation
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

What makes Humanin significant in neurodegeneration research?
Humanin was the first peptide shown to rescue neurons from Alzheimer's-related cell death, making it a landmark compound in the study of mitochondrial-to-nuclear cytoprotective signaling. It acts through unique receptor complexes not targeted by current Alzheimer's drugs.
How do Humanin levels change with age?
Circulating Humanin levels drop 30–50% between ages 20–70, making it one of the steepest age-related declines of any known peptide. This age-related depletion correlates with increased insulin resistance, cardiovascular disease, and cognitive decline.

8 References

  1. Network Topology and Interactomic Analysis Reveal the Regulatory Framework of the Humanin Protein Family (MTRNR2Lx Class) PubMed (2026). Shahzaib M, et al.. View source
  2. S14G-humanin (HNG) ameliorates diabetic nephropathy tubular injury by inhibiting Z-DNA/ZBP1-mediated necroptosis PubMed (2026). Liu Y, et al.. View source
  3. Humanin peptide ameliorates reproductive dysfunction and restores neuroendocrine mechanisms in SSRI-treated male rats PubMed (2026). Köm Akipek RE, et al.. View source
  4. Neuroprotective effect of intraperitoneal Humanin-G in retinal degeneration of Royal College of Surgeons rats PubMed (2026). Lin B, et al.. View source

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9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.

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