Humanin

HN, humanin peptide, MT-RNR2 peptide; analogues HNG (S14G-humanin), HNGF6A, colivelin

Immune & bioregulators

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Summary

Class: Naturally occurring 24-amino-acid peptide encoded inside the mitochondrial genome (the 16S rRNA gene, MT-RNR2); the first "mitochondrial-derived peptide" described
Mechanism: Protects cells from stress-induced death by blocking the pro-death protein Bax, binding IGFBP-3, and signalling through cell-surface receptors (FPRL1/FPR2 and a CNTFR/WSX-1/gp130 complex) — shown in cells and rodents
Routes studied: Intraperitoneal, intravenous, intracerebroventricular and subcutaneous injection in rodents; no route studied in humans
Dose range reported: Rodent studies: roughly 0.1–4 mg/kg/day of humanin or its potent analogue HNG, depending on model. Community reports are sparse and typically describe low-milligram subcutaneous doses a few times a week, usually of HNG. No human dose exists
Half-life: Not characterised in humans. Native humanin is cleared quickly; the S14G analogue (HNG) was designed to be more stable and ~1,000-fold more potent in cells
Storage: Lyophilised: refrigerate, protect from light. Reconstituted: refrigerate; community practice is use within ~4 weeks
Regulatory status: Not approved anywhere; no clinical trials of administered humanin registered as of review date †

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

1What it is

Humanin is a small peptide that the body makes itself, and unusually, the instructions for it sit in mitochondrial DNA rather than in the cell nucleus. It was found in 2001 by a Japanese group screening a library of genes from the surviving brain tissue of a person who had died with Alzheimer's disease; the peptide protected neurons from Alzheimer's-related toxicity, which is where the name comes from (Hashimoto 2001, PNAS). Two other groups found the same molecule in the same year through unrelated searches, one as a partner of the pro-death protein Bax and one as a binder of IGFBP-3.

It circulates in human blood, and levels appear to fall with age. Children of centenarians have been reported to carry higher levels than age-matched controls, which is where much of the longevity interest comes from. The version most often discussed as a research compound is HNG, a single-substitution analogue (glycine replacing serine at position 14) that is far more potent in cell models than the native peptide. It is important to know which version a study used.

2How it's thought to work

Humanin seems to act both inside and outside cells:

Inside the cell. binds Bax and related proteins and stops them moving to the mitochondrial membrane, which blocks one of the main routes to programmed cell death.

IGFBP-3. binds insulin-like growth factor binding protein 3, which may modulate IGF-1 signalling and IGFBP-3's own pro-death actions.

Receptors. acts on the formyl peptide receptor FPRL1/FPR2 and on a three-part receptor (CNTFR, WSX-1, gp130) that switches on STAT3 survival signalling (Hashimoto 2009, Mol Biol Cell).

Metabolism. in rats, central (brain) delivery of HNG increased whole-body insulin sensitivity through the hypothalamus (Muzumdar 2009, PLoS One).

Humanin, the first mitochondrial-derived peptide described, encoded within the mitochondrial 16S rRNA gene. It is released under cellular stress and binds a receptor complex that holds apoptosis off, which is the basis of its neuroprotective and metabolic claims.Schematic — not to scale

All of this comes from cell culture and rodent work.

3What the research shows

Graded C/D

Neuroprotection

Protects cultured neurons from amyloid-beta and familial Alzheimer's mutations (Hashimoto 2001); HNG improved memory in mouse Alzheimer's models and reduced amyloid load in some studies. No human trial. [1]

Insulin sensitivity and metabolic effects

Central and peripheral HNG improved glucose handling in rats and reduced visceral fat in some rodent studies (Muzumdar 2009, PLoS One). Levels of circulating humanin in humans correlate inversely with some markers of insulin resistance in observational work. [4]

Heart protection

HNG given at reperfusion reduced infarct size and improved function in mouse models of heart attack (Muzumdar 2010, Arterioscler Thromb Vasc Biol). Mouse only. [5]

Graded C/B (observational)

Lifespan and healthspan

Humanin levels decline with age in mice, rhesus monkeys and humans; sustained HNG treatment in middle-aged mice improved metabolic markers and some healthspan measures, with lifespan effects that were modest or mixed (Yen 2020, Aging). Higher levels in centenarians' offspring are observational and do not show that giving humanin produces longevity. [7]

Graded C/D

Vascular, kidney and eye protection

Reported in rodent models of atherosclerosis, kidney injury and retinal cell stress. All preclinical.

4Reported side effects and interactions

Literature-reported

No human safety data exist for administered humanin or HNG. Rodent studies at tested doses report few adverse effects.

Community-reported

very few reports; those that exist describe injection-site irritation and occasional fatigue or headache. Too sparse to characterise.

Theoretical. a peptide whose defining action is to block cell death could in principle protect cancer cells as well as healthy ones; some tumours express humanin, and this has been raised as a concern in the literature but not tested in humans. Effects on IGF signalling via IGFBP-3 are unpredictable.

Interactions. none established.

Markers researchers commonly monitor

No humanin-specific clinical markers are established. The physiology suggests watching:

Marker	Why it's watched
Fasting glucose, insulin and HbA1c	the main metabolic effect reported in rodents is improved insulin sensitivity.
IGF-1 and IGFBP-3	humanin binds IGFBP-3, so the IGF axis is the most plausible place for an unexpected shift.
Lipid panel	rodent work reports changes in cholesterol handling.
General baseline: CBC, comprehensive metabolic panel (CMP), liver enzymes	standard for any unstudied injectable.
Circulating humanin itself can be measured by research ELISA but there is no clinical reference range

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

5Reconstitution and handling

Usually supplied as powder in small vials (often 5–10 mg). with , swirl gently, protect from light. Because native humanin and HNG differ a great deal in potency, check which one the vial actually contains before any calculation.

Open in calculator, pre-loaded →

6Commonly studied alongside

MOTS-c and SS-31 (the three are often grouped as "mitochondrial" peptides, but no combined study exists), epitalon (community pairing only).

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 as far as we can confirm †
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Prohibited by WADA under S0 (non-approved substances) †

8Open questions

Does injected humanin or HNG reach meaningful tissue levels in humans, and for how long?
Is the age-related decline in circulating humanin a cause of anything, or just a marker?
Does blocking cell death in healthy tissue also shield pre-cancerous cells?
Which receptor matters most , and do the native peptide and HNG behave the same way?

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
2Ikonen M et al. (2003). Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc Natl Acad Sci USA. PubMed · DOI
3Hashimoto Y et al. (2009). Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor α/WSX-1/gp130. Mol Biol Cell. PubMed · DOI
4Muzumdar RH et al. (2009). Humanin: a novel central regulator of peripheral insulin action. PLoS One. PubMed · DOI
5Muzumdar RH et al. (2010). Acute humanin therapy attenuates myocardial ischemia and reperfusion injury in mice. Arterioscler Thromb Vasc Biol. PubMed · DOI
6Lee C, Yen K, Cohen P (2013). Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol Metab. PubMed · DOI
7Yen K et al. (2020). The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging. PubMed · DOI

† 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

25 Oct 2026Profile published — awaiting medical review

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