Humanin
Humanin (HN) — Mitochondria-Derived Peptide
Humanin is a 21-amino-acid peptide encoded by the mitochondrial 16S rRNA gene — the first mitochondria-derived peptide discovered. Circulating Humanin levels decline with age and are inversely correlated with insulin resistance, Alzheimer's disease risk, and cardiovascular disease. Research focuses on neuroprotection, insulin sensitisation, and cardiovascular protection.
Mechanism of Action
Humanin was originally identified for its ability to block Alzheimer's disease-associated neuronal death triggered by amyloid beta and other cytotoxic proteins. It binds IGFBP-3 (insulin-like growth factor binding protein 3) and the tripartite receptor complex (CNTFR/WSX-1/GP130), activating JAK2/STAT3 and MAPK survival pathways.
Humanin improves insulin sensitivity via STAT3-mediated hepatic insulin signalling and reduces circulating IGF-1 — a combination that is metabolically protective. In animal models, Humanin administration normalises blood glucose and reduces adiposity in diabetic models.
Cardiovascular effects include inhibition of macrophage foam cell formation (reducing atherosclerotic plaque) and anti-apoptotic activity in cardiomyocytes following ischaemic injury.
Research Evidence
Humanin research spans neuroprotection, metabolism, and cardiovascular biology. Plasma Humanin levels in centenarians are significantly higher than age-matched controls, suggesting its biological relevance to exceptional longevity.
Humanin Protects Against Alzheimer's Disease-Like Neurodegeneration
Humanin blocked Alzheimer's-related neuronal apoptosis triggered by multiple AD-associated pathological proteins, establishing it as a broad neuroprotective peptide relevant to neurodegeneration.
Higher Plasma Humanin Levels in Centenarian Offspring
Offspring of centenarians had significantly higher circulating Humanin levels than age-matched controls, and Humanin correlated inversely with insulin resistance and atherosclerosis markers — implicating it in familial longevity.
Typical Research Protocol
Human dosing protocols are not established. Analogue HNG (Humanin-G) with a glycine substitution has 1,000-fold greater potency in some bioassays and is being studied as a more practical clinical candidate.
Safety Profile
Reported Side Effects
- Injection site reaction
- Mild fatigue (transient)
Contraindications
- IGF-1 pathway-sensitive malignancies (theoretical)
- Pregnancy (no data)
Common Research Stacks
Frequently Asked Questions
What happens to Humanin levels as we age?
Circulating Humanin levels decline progressively with age, with the sharpest decline occurring after age 60. This decline correlates with rising rates of metabolic dysfunction, cognitive decline, and cardiovascular disease. Whether restoring Humanin levels with exogenous supplementation produces the same protective effects remains an active research question.
Can Humanin protect against Alzheimer's disease?
Humanin was originally discovered through a screen for proteins that block Alzheimer's-associated neuronal death. It protects against amyloid beta, presenilin mutant-induced, and other AD-related cell death pathways. In transgenic AD mouse models, Humanin administration reduced cognitive decline and amyloid pathology. Human trials in AD populations are not yet published, but the mechanistic basis for a protective role is strong.
What is HNG (Humanin-G) and how is it different?
HNG (Humanin-G) is an analogue of Humanin with a glycine substitution at position 14 that produces approximately 1,000-fold greater bioactivity in some bioassays. Because of its superior potency, much current research uses HNG rather than native Humanin to achieve meaningful effects at practical doses. HNG is increasingly the preferred form in research protocols.
Does Humanin have anti-diabetic properties?
Yes — Humanin improves insulin sensitivity through multiple mechanisms: STAT3-mediated hepatic insulin signalling enhancement, reduction of hepatic glucose output, and inhibition of beta-cell apoptosis. In diabetic mouse models, Humanin normalises blood glucose and reduces HbA1c. Human data is not yet available, but its metabolic profile suggests utility in insulin resistance and type 2 diabetes research.
Is there a relationship between Humanin and cardiovascular disease?
Yes — circulating Humanin levels correlate inversely with atherosclerosis severity and cardiovascular disease risk. Humanin inhibits macrophage foam cell formation (a critical step in atherosclerotic plaque development), protects cardiomyocytes from ischaemic damage, and improves endothelial cell survival under stress. These cardiovascular protective properties make Humanin one of the most multi-targeted longevity peptides currently in research.
Key Research References
- Hashimoto Y et al. (2001). A rescue factor abolishing neuronal cell death by Alzheimer's disease proteins. Science.
- Muzumdar RH et al. (2009). Acute humanin therapy attenuates myocardial ischaemia. Arterioscler Thromb Vasc Biol.
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