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Explore  /  Humanin (HN / HNG / S14G-Humanin)

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Humanin (HN / HNG / S14G-Humanin)

C

lead outcome

Longevity biomarker (levels correlate with…

grades vary by outcome ↓

Peptide

also called — Humanin · HN · HNG / S14G-Humanin / [Gly14]-Humanin (the potent synthetic analog) · HNGF6A (a further-modified metabolic analog) · rattin (the rat ortholog). INCI: none

mitochondriallongevity-biomarker(preclinical:) neuroprotection (Alzheimer's / amyloid)insulin-sensitisingcardioprotection

The mitochondrial trio's third face — and the register's clearest "gorgeous mechanism, zero human trials" case. Three honest points define this entry: (1) it is the founding member of the mitochondrial-derived peptide (MDP) family — the same class as MOTS-c (#10) — with an unusually rich, well-mapped molecular biology; (2) it is a genuine longevity biomarker (higher in centenarians and their children) — but a biomarker is not a drug, and there is not one completed human trial of giving it; (3) almost all the impressive preclinical data uses the HNG analog (~1000× more potent), not the native "Humanin" sold in research channels — so even the animal data doesn't map cleanly onto the product.

In brief

Humanin is the founding mitochondrial-derived peptide — a 24-amino-acid signal encoded in mitochondrial DNA, discovered in 2001 from an Alzheimer's-resistant neuron. Its molecular biology is unusually well-mapped: it binds a specific cell-surface receptor complex to switch on survival signalling, directly blocks the cell-death protein BAX, and modulates IGF-1 signalling — engaging two of the most conserved longevity pathways (mitochondrial health and IGF-1/insulin) at once. In humans, circulating humanin falls with age, is lower in Alzheimer's and coronary disease, and is higher in centenarians and their children — making it a compelling longevity biomarker. But that is the ceiling of the human evidence: it is correlational and observational. There is no completed interventional human trial of administering humanin for anything, no established human pharmacokinetics, and no dose-ranging data — and most of the striking preclinical work used the HNG analog (~1000× more potent), not the native peptide typically sold. It is an intriguing hypothesis, not a demonstrated therapy.

Legal standing, by region

European Union

Not FDA-approved (gray-market)

not approved anywhere for any indication; not a cosmetic; investigational research peptide only. No EMA/FDA marketing authorisation, no compounding pathway.

Evidence, by outcome

How we grade →

An honest grade per outcome — drawn from the evidence, not any catalogue. Hype and undemonstrated marketing claims grade low.

OutcomeEvidence base · effectGrade

Longevity biomarker (levels correlate with lifespan/health)

This is the strongest human evidence — but it's a biomarker correlation, not proof that giving humanin helps. Human association studies are even called "equivocal" in some reviews. Biomarker ≠ drug

Multiple human observational/epidemiological datasets (USC, Barzilai): humanin ↓ with age, ↓ in AD/CAD, ↑ in centenarians + their offspring; correlates across mammalian species

C

Neuroprotection / Alzheimer's (the discovery context)

Powerful mechanism, zero completed human trials; no RCT shows exogenous humanin prevents or treats AD. Founding story ≠ clinical proof

Rich preclinical: blocks amyloid-beta toxicity, prevents tau hyperphosphorylation, anti-apoptotic in neuron/animal models (mostly HNG)

F

Insulin sensitivity / metabolic

Preclinical rodent only, small n; CNS-mediated mechanism; not shown in humans

Rodent clamp studies (Muzumdar 2009 — central STAT3-mediated; HNGF6A analog lowered glucose in diabetic rats)

F

Cardioprotection (ischemia, age-related fibrosis)

Animal-only; native-vs-HNG gap applies

Animal: ischemia-reperfusion protection; 14-month HNG dosing prevented age-related myocardial fibrosis in aged mice

F

"Anti-aging / healthspan" (the popular use)

The headline longevity-therapeutic claim is animal + biomarker, not human-interventional. This is what most buyers want — and it's unproven in people

Transgenic worms + multiple mammalian species (levels track lifespan); HNG improved healthspan markers, lowered inflammation in mice

F

Safety (exogenous administration in humans)

Endogenous peptide (present in everyone), which is reassuring mechanistically, but injected exogenous safety/PK is simply not characterised in humans

No completed human trials → no human safety dataset

—

Disclosure

Vallydia sells its own cosmetic serums, and some ingredients graded here belong to the same categories as those products. Grades are drawn from the published evidence by the method we publish, and applied to our own ingredients on the same terms — our copper-peptide serum is graded no more kindly than the peptides it competes with. We disclose the interest so you can weigh it.

Trade names shown here (for example Matrixyl, Argireline, Syn-Ake) are the property of their respective owners and are used only to identify the ingredient under discussion. Their appearance implies no affiliation with, or endorsement by, the proprietor.

Evidence changes

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Identity

a 24-amino-acid peptide (< 40 aa → peptide) translated from a short open reading frame in the 16S ribosomal RNA gene (MT-RNR2) of mitochondrial DNA. This mitochondrial (not nuclear) origin places it in a molecularly distinct class: the mitochondrial-derived peptides (MDPs), of which Humanin is the founding, first-described, and most-characterised member — the same family as MOTS-c (#10) and the SHLP1-6 peptides.

Mechanism (as proposed)

Humanin is cytoprotective through several mapped routes: (1) it binds a trimeric receptor complex (CNTFR / WSX-1 / gp130) to activate JAK2/STAT3 survival signalling; (2) it directly antagonises BAX, a pro-apoptotic protein, preventing it from permeabilising the mitochondrial membrane (blocking the cell-death cascade); (3) it binds IGFBP-3, modulating IGF-1 signalling and apoptosis — tying it into the conserved IGF-1/insulin longevity axis; (4) it engages formyl-peptide receptors (FPRL1/2) and activates PI3K/Akt, upregulating anti-apoptotic BCL-2 and lowering ROS. This mechanistic richness is exactly why it's scientifically exciting — and it makes the absence of human interventional data all the more conspicuous.

Chemical identifiers

Cross-reference identifiers for the authoritative external databases — not a recipe, and nothing about how to use it.

PubChem CID16131438

InChIKeyDPEUWKZJZIPZKE-OFANTOPUSA-N

SMILESCC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](C)NC(=O)[C@H](CCSC)N

UNIIH975EUX36G

ChEMBLCHEMBL4447799

via PubChem exact-name match (Humanin) · high confidence

Sources — 5 cited

01Hashimoto Y, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ. PNAS. 2001 (original discovery).

02Muzumdar RH, et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One. 2009 (rodent metabolic).

03Cohen P / Yen K, et al. & Barzilai N, et al. — humanin, IGF-1 signalling, centenarian/offspring cohorts (USC & Albert Einstein).

04The mitochondrial-derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY). 2020 (worms + multiple mammals + centenarian offspring; notes human associations are equivocal).

05Coradduzza et al. (Biology, 2023) & Karachaliou/Livaniou (2023) — reviews explicitly flagging absence of human clinical data as the primary limitation.

Updated 2026-07-13 (watch for any first-in-human interventional trial — that would change the grades materially)

Grades reflect the published evidence, not our interest. No dosing, reconstitution, or administration is published for research compounds — that restraint is deliberate.

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Protein (not a peptide)

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This site provides neutral scientific reference and sells only products lawful in your region. Nothing here is medical advice, a recommendation, or an offer to supply unapproved medicines. No dosing or administration is published for research compounds. Cosmetic peptides per Regulation (EC) 1223/2009. Unapproved injectable peptides are neither sold nor advertised in the EU (Directive 2001/83/EC, Title VIII). © 2026 Vallydia.