HNG

HNG, [Gly14]-humanin, S14G-HN, humanin G, "potent humanin analogue"

Longevity & cellular

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Summary

Class: Synthetic 24-amino-acid analogue of the mitochondrial-derived peptide humanin, with serine at position 14 replaced by glycine
Mechanism: Mimics humanin — binds a cell-surface receptor complex (CNTFR/WSX-1/gp130) and intracellular pro-apoptotic proteins (Bax, IGFBP-3), protecting cells from stress and death — but roughly 1,000 times more potent than the natural peptide in cell assays
Routes studied: Intraperitoneal, intravenous, intranasal and intracerebroventricular injection (rodents); subcutaneous (community)
Dose range reported: Rodent: ~0.1–4 mg/kg/day intraperitoneal in most metabolic and neuro studies; 2 mg/kg IV in cardiac ischaemia work. Community-reported: 1–5 mg subcutaneous daily or several times weekly. No human dose exists
Half-life: Not characterised in humans. Humanin itself is cleared quickly; the S14G substitution improves stability in cell media, but systemic pharmacokinetics are poorly described
Storage: Lyophilised: refrigerate, protect from light. Reconstituted: refrigerate, use within ~4 weeks (community practice)
Regulatory status: Not approved anywhere; research chemical only

Doses are as reported in studies or by the community — never recommendations.

1What it is

Humanin is a short peptide encoded in mitochondrial DNA (inside the 16S ribosomal RNA gene) that cells release under stress; it has its own profile (Humanin, #15). HNG is the laboratory-made version in which one amino acid — serine 14 — is swapped for glycine. That single change was found in the original 2001 discovery work to make the peptide about a thousand times more potent at protecting neurons from Alzheimer's-related toxicity, so almost all animal research on "humanin" since then has actually used HNG. When you read a mouse study of humanin, check which molecule was injected; it is usually this one.

HNG is a synthetic research compound. The natural peptide circulates in human blood and declines with age; HNG does not occur naturally. There are no human trials of HNG for any indication.

2How it's thought to work

Humanin and HNG are thought to act through two routes:

Outside the cell. binding to a receptor complex made of CNTFR, WSX-1 and gp130, which switches on STAT3 and other survival signalling. A second G-protein-coupled receptor (FPRL1/FPR2) has also been implicated.

Inside the cell. binding to pro-apoptotic proteins such as Bax and to IGFBP-3, preventing them from triggering cell death.

Downstream, HNG increases insulin sensitivity in rodents via hypothalamic signalling, reduces oxidative stress, improves mitochondrial function, and dampens inflammatory signalling.

The glycine substitution does not change the mechanism; it increases potency, probably through better receptor binding and resistance to breakdown.

Proposed: an analogue of humanin with a single substitution (serine to glycine at position 14) reported to be far more potent than the parent peptide in cell and animal work. The mechanism drawn is humanin's; the difference is potency, not pathway.Schematic — not to scale

3What the research shows

Neuroprotection and Alzheimer's models

HNG protected cultured neurons from amyloid-β and mutant APP/presenilin toxicity in the original work (Hashimoto 2001, PNAS). In triple-transgenic Alzheimer's mice, HNG reduced amyloid accumulation and improved memory (Niikura 2011, PLoS One). Later work reported that HNG given to middle-aged mice prevented age-related cognitive decline, and that circulating humanin levels tracked cognitive age in humans — the human part refers to native humanin, not HNG (Yen 2020, Sci Rep). [1][2][8]

Metabolism and insulin sensitivity

Central or peripheral HNG improved insulin sensitivity in rats, partly through hypothalamic STAT3 signalling (Muzumdar 2009, PLoS One). Related rodent work reports lower glucose and better glucose tolerance in diabetic models. [3]

Cardiac ischaemia-reperfusion

HNG given at reperfusion reduced infarct size and improved cardiac function in mice (Muzumdar 2010, Arterioscler Thromb Vasc Biol). [4]

Atherosclerosis and endothelial function

HNG preserved endothelial function and slowed plaque progression in ApoE-deficient mice on a high-cholesterol diet (Oh 2011, Atherosclerosis). [5]

Protection of germ cells and other tissues from chemotherapy

Rodent studies report HNG reduces germ-cell apoptosis caused by cyclophosphamide and protects other tissues from chemotherapy and radiation stress, without protecting the tumour in the models tested †.

Retinal cells (AMD model)

HNG protected retinal pigment epithelium cell lines carrying AMD-patient mitochondria from damage (Nashine 2017, Cell Death Dis). . [7]

Human outcomes

None. Everything above is rodent or cell. Community reports of "better energy", sleep or cognition are anecdotal.

4Reported side effects and interactions

Literature-reported

No controlled human safety data. Rodent studies at the doses above report no obvious toxicity. Humanin, and therefore HNG, lowers IGF-1 signalling in some models, which cuts both ways for longevity and growth.

Community-reported

Injection-site reactions, transient fatigue or "flat" feeling, headache; some report lower appetite. Reports are sparse and unverified.

Theoretical. An anti-apoptotic peptide that protects stressed cells from dying could, in principle, protect pre-malignant cells too; the rodent chemotherapy work argues against this in the models tested, but human data are absent. Effects on the IGF axis and on glucose are plausible and unmeasured in humans.

Interactions. None established. Additive glucose-lowering with insulin or oral hypoglycaemics is plausible from the rodent data.

Markers researchers commonly monitor

No markers are established in human literature for HNG. Based on rodent pharmacology, members commonly discuss:

Marker	Why it's watched
Fasting glucose, fasting insulin, HbA1c	HNG improves insulin sensitivity in rodents; the most mechanism-relevant markers.
IGF-1	humanin signalling interacts with the IGF axis; direction in humans unknown.
Lipid panel and hs-CRP	the atherosclerosis and inflammation rationale.
Native humanin level (research assay)	not available in standard clinical labs; mentioned because the Yen 2020 human data used it, but there is no validated clinical assay.
CBC and CMP	general baseline for an injected compound with no human safety data.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Usually supplied as powder in 5 mg or 10 mg vials. with ; swirl, do not shake. A 24-amino-acid peptide with a hydrophobic core — some community reports note it dissolves slowly; allow time rather than agitating. Protect from light.

Open in calculator, pre-loaded →

6Commonly studied alongside

Humanin (#15, the native peptide — the two are often conflated); MOTS-c and SHLP-2 (#87), the other mitochondrial-derived peptides; in community "mitochondrial" stacks alongside SS-31/elamipretide and NAD precursors, with no combination data.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Not on the FDA 2023 Category 2 compounding list to our knowledge †. Research chemical only
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved; prescription-only scheduling for peptides for injection †
South Africa	Not registered
Sport (WADA)	Not specifically named. S0 (non-approved substance) applies †; because it modulates IGF signalling, S2 classification is also arguable

8Open questions

Does HNG have any effect in humans at all? No trial has been run.
Pharmacokinetics: how long does injected HNG circulate, and does it reach the brain?
Long-term safety of chronic anti-apoptotic signalling.
Whether the human associations seen with native humanin levels say anything about giving an analogue.

9References

1Hashimoto Y et al. (2001). A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ. Proc Natl Acad Sci USA. PubMed · DOI
2Niikura T, Sidahmed E, Hirata-Fukae C, Aisen PS, Matsuoka Y (2011). A humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic mice. PLoS One. PubMed · DOI
3Muzumdar RH et al. (2009). Humanin: a novel central regulator of peripheral insulin action. PLoS One. PubMed · DOI
4Muzumdar RH et al. (2010). Acute humanin therapy attenuates myocardial ischemia and reperfusion injury in mice. Arterioscler Thromb Vasc Biol. PubMed · DOI
5Oh YK et al. (2011). Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice. Atherosclerosis. PubMed · DOI
6Yen K, Lee C, Mehta H, Cohen P (2013). The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. PubMed · DOI
7Nashine S, Cohen P, Chwa M, Kenney MC (2017). Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage. Cell Death Dis. PubMed · DOI
8Yen K et al. (2020). Humanin prevents age-related cognitive decline in mice and is associated with improved cognitive age in humans. Sci Rep. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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