Humanin
Also known as: HN, HNG (Gly14-Humanin — more potent analog), Mitochondrial-derived peptide
Humanin is a research compound not approved for human use. For informational purposes only.
Overview
Humanin is a 21-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of the mitochondrial genome — discovered in 2001 through a screen for neuroprotective factors in Alzheimer's disease. It is the founding member of a new class of peptide hormones encoded by mitochondria, not nuclear DNA. Circulating humanin levels decline sharply with age and are inversely correlated with cardiovascular disease risk, insulin resistance, and cognitive decline.
Research Summary
Humanin acts through multiple receptors (CNTFR/WSX-1/gp130 trimeric complex and FPRL1) to exert neuroprotection, cardioprotection, and metabolic effects. Key findings: humanin inhibits neuronal apoptosis in Alzheimer's disease models by blocking IGFBP-3 death signaling, reduces cardiovascular disease markers in clinical studies, improves insulin sensitivity in diabetic models, and reduces oxidative stress. IGF-1 downregulates humanin production — individuals on GH/IGF-1 therapies may have suppressed endogenous humanin. Centenarians have elevated humanin levels compared to age-matched controls.
Dosing Range
low
100mcg
moderate
500mcg
high
2mg
Units: mcg · Frequency: Daily or 3–5x weekly
Dosing ranges are aggregated from preclinical research and community protocols. Not medical dosing guidance.
Administration Routes
Reconstitution Notes
Reconstitute with bacteriostatic water to 1mg/mL. Stable 28 days refrigerated. HNG (Gly14-Humanin) is a synthetic analog ~1000x more potent — adjust dosing accordingly if using HNG variant.Step-by-step reconstitution guide →
Supplies you'll need
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Reported Side Effects
- Generally well-tolerated in animal studies
- No significant adverse effects reported at research doses
- Potential interaction with GH/IGF-1 axis (IGF-1 suppresses humanin production)
- Long-term human safety data limited
Research Papers
3 peer-reviewed sourcesCommunity Experiences
Aggregated from public forums. Anecdotal — not clinical evidence.
Longevity community interest in humanin as an anti-aging intervention — centenarian data and protocol discussions.
View original threadResearch peptide community early adoption of humanin — dosing protocols and stacking with other anti-aging peptides.
View original threadOverview
Humanin is unlike any other peptide in this library: it is encoded by the mitochondrial genome, not nuclear DNA. Mitochondria — the cellular power plants — retain their own small genome (16,569 base pairs in humans, encoding 37 genes). Humanin is encoded within the 16S rRNA gene of this genome and is secreted from cells to act as a circulating hormone.
Its discovery opened an entirely new field: mitochondria-to-cell signaling via peptide hormones. Several other mitochondrial-derived peptides (MDPs) have since been identified (MOTS-c, SHLP1-6), but humanin remains the most characterized.
Why Humanin Declines with Age
Humanin levels decrease predictably with age in humans — a finding consistent across multiple cohort studies. The proposed mechanisms:
- Age-related mitochondrial dysfunction reduces production capacity
- Increased oxidative stress impairs mitochondrial translation
- Rising IGF-1 signaling (in midlife) suppresses humanin secretion
Importantly, centenarians have elevated humanin levels compared to average 70-year-olds — suggesting either that high humanin promotes longevity, or that genetically robust mitochondria produce more humanin and also support longer life.
Multi-System Protection
Neuroprotection (Alzheimer's)
Humanin was discovered by screening for factors that protected neurons from Alzheimer's-associated amyloid beta toxicity. It:
- Blocks IGFBP-3/IGFBP-3 receptor-mediated neuronal death
- Reduces amyloid beta-induced apoptosis
- Crosses the blood-brain barrier
Cardiovascular
Epidemiological data shows plasma humanin is inversely correlated with:
- Carotid intima-media thickness (atherosclerosis marker)
- LDL oxidation
- Inflammatory markers (CRP, IL-6)
Metabolic
- Improves insulin sensitivity in diabetic models
- Reduces ceramide-driven insulin resistance
- Improves mitochondrial biogenesis in muscle
The IGF-1 / Humanin Tradeoff
Mechanistic studies show IGF-1 downregulates humanin production. This raises an interesting question for longevity: moderate IGF-1 suppression (as seen in caloric restriction and certain longevity interventions) may partly explain benefits through humanin elevation. This is an active area of research.
HNG: The Potent Analog
Gly14-Humanin (HNG) — a synthetic variant where glycine replaces serine at position 14 — is approximately 1,000x more potent than native humanin in neuroprotection assays. Research use of HNG allows nanogram-scale dosing with equivalent effects.
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