Humanin
Humanin is a small mitochondria-encoded signaling peptide studied for cytoprotective effects in cells and animals. It is a research compound with no FDA approval and no completed human trials of administered humanin — the only human evidence measures the body's own (endogenous) levels.
Key facts
- Category
- Energy & metabolism
- Legal / FDA status
- Research compound (not FDA-approved); preclinical — no established human exogenous dose
- Half-life
- Short and characterized only in rodents (native humanin ≈ 30 minutes in mice); not characterized in humans. Stability-enhanced analogs (HNGF6A) and PEGylation extend it
- Typical form
- Lyophilized research powder (research-use-only); analogs such as HNG are the most-studied forms in animals
- Also known as
- HN, mitochondrial-derived peptide (MDP), HNG (S14G-humanin), HNGF6A
Humanin is a small mitochondria-encoded signaling peptide — the first "mitochondrial-derived peptide" (MDP) discovered, in 2001. It has been studied for cytoprotective effects in cells and animals. It is a research compound, not an approved medicine, and there are no completed human trials of administered humanin. This page is educational and is not medical advice; WikiPeps sells nothing and gives no dosing or sourcing guidance.
The key honesty point: the only human evidence about humanin measures the body's own, naturally produced levels — not the effects of injecting it. Don't confuse "low endogenous humanin is associated with aging" with "taking humanin is proven safe or beneficial." Those are very different claims.
What is Humanin?#
Humanin is a 24-amino-acid peptide encoded within the mitochondrial MT-RNR2 (16S rRNA) gene. It acts as a retrograde signal — a message from the mitochondria to the rest of the cell — and is broadly cytoprotective (cell-protecting). Stability-enhanced analogs such as HNG (S14G-humanin) are the most-studied forms in animal experiments.
How is it thought to work?#
- Inside the cell, humanin is anti-apoptotic: it binds and neutralizes pro-death proteins (BAX, tBID, BimEL) to keep the mitochondrial membrane intact, and binds IGFBP-3.
- Outside the cell, it signals through a surface receptor complex (CNTFR / WSX-1 / gp130) and formyl-peptide receptors, switching on pro-survival STAT3 and ERK1/2 pathways and reducing oxidative stress.
What is Humanin studied for?#
Predominantly preclinical — cells and animal models — across neuroprotection (Alzheimer's/amyloid-β, stroke, Parkinson's, TBI), metabolic biology (insulin secretion and sensitivity, β-cell survival, diet-induced obesity), cardioprotection, and aging/longevity. The human evidence is observational only: endogenous levels decline with age, are lower in Alzheimer's CSF, and are higher in centenarians' offspring. These are correlations, not interventional results.
Is there a human dose?#
No — preclinical / no established human dose. No completed human clinical trials of administered humanin exist, and there is no validated human pharmacokinetic or dosing protocol. Quantitative dosing in the literature is animal-only (for example, HNG ~4 mg/kg in mice, given intraperitoneally) and does not translate to a human protocol. Vendor/community "protocols" are extrapolated and unsupported.
Safety#
Unknown in humans — no clinical safety, toxicology, chronic-exposure, or drug-interaction data. In animals, humanin and analogs have generally been well tolerated at tested doses, but endogenous-level associations cannot inform the safety of injecting it. Because it modulates apoptosis, IGF/IGFBP-3, and metabolism, theoretical effects on cell-survival pathways relevant to cancer biology remain unstudied. Treat it as experimental with an undefined safety profile.
The bottom line#
Humanin is a fascinating mitochondrial-derived peptide with real, mostly-preclinical science behind it — and no human dose, no human safety data, and no completed trials of administering it. The encouraging human findings are about the body's own humanin, not about supplementation. Anything resembling use belongs with a licensed clinician.
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Frequently asked questions
What is Humanin?
- Humanin is a 24-amino-acid peptide encoded within mitochondrial DNA (the MT-RNR2 / 16S rRNA region), discovered in 2001. It was the first 'mitochondrial-derived peptide' identified and acts as a cytoprotective, mitochondria-to-nucleus signaling molecule. It is a research compound, not an approved medicine.
Is Humanin FDA-approved or proven in people?
- No. Humanin is not FDA-approved for any indication, and there are no completed human clinical trials of administered (exogenous) humanin or its analogs. The evidence is predominantly preclinical (cells and animals). Human data are observational only — measuring the body's own naturally produced humanin.
Is there an established human dose of Humanin?
- No — preclinical / no established human dose. There is no validated human pharmacokinetic or dosing protocol. All quantitative dosing in the literature is animal-only (e.g., HNG ~4 mg/kg in mice, intraperitoneal). Any 'protocol' on vendor or community sites is extrapolated and not supported by clinical data; decisions belong with a licensed clinician.
What does the human evidence actually show?
- Only correlations from observational studies of endogenous humanin: circulating and CSF levels tend to decline with age, are lower in Alzheimer's CSF, and are higher in the offspring of centenarians. These are hypothesis-generating associations about the body's own humanin — they do not show that injecting humanin is safe or effective.
What are the safety concerns with Humanin?
- Human safety is unknown — there are no clinical safety or toxicology studies, no chronic-exposure data, and no defined therapeutic window. In animals it has generally been well tolerated, but because it modulates apoptosis, IGF/IGFBP-3, and metabolic signaling, theoretical effects on cell-survival pathways (relevant to cancer biology) remain unstudied in humans. Treat it as experimental with an undefined safety profile.
References
- 1.Pharmacokinetics and Tissue Distribution of Humanin and Its Analogues in Male Rodents (rodent PK — closest 'dosing' reference; no human dose) — Endocrinology — PMID 23836030 · 2013
- 2.The Emerging Role of the Mitochondrial-Derived Peptide Humanin in Stress Resistance (foundational review) — Journal of Molecular Endocrinology — Yen, Lee, Mehta, Cohen — PMID 23239898 · 2013
- 3.Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans (endogenous-level association) — Scientific Reports — PMID 30242290 · 2018
- 4.Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives — Biology (Basel) — PMID 38132360 · 2023
- 5.The Mitochondrial-Derived Peptide Humanin is a Regulator of Lifespan and Healthspan — Aging (Albany NY) — PMID 32575074 · 2020
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