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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-mappe

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

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

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.

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.
Review status
Not yet reviewed

A credentialed reviewer (PharmD / PhD / MD) will be named before this entry is finalised. Until then, treat it as a working draft. Last updated July 2026 (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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Humanin — the founding mitochondrial peptide: rich biology, biomarker status, no human trials · Vallydia