Neuroprotection against amyloid toxicity [1][2]
The founding finding — humanin protects neurons from amyloid-beta-induced apoptosis in culture and in rodent models.
PrecisePep/Peptide Library/Humanin
Mitochondrial & Bioenergetic
Humanin
HN · HNG (potent analogue) · mitochondrial-derived peptide
The first mitochondrial-derived peptide ever identified — discovered in a search for what protects surviving neurons in Alzheimer brains, and still almost entirely a laboratory compound.
00 Overview
Humanin has one of the better origin stories in cell biology. It was identified in a screen of the surviving neurons in the occipital lobe of an Alzheimer disease brain — researchers asked what those cells were expressing that their dead neighbours were not, and humanin was the answer.[1]
It turned out to be the first mitochondrial-derived peptide: a short open reading frame within the mitochondrial genome encoding a secreted, cytoprotective signalling peptide. MOTS-c was found later, in the same conceptual family. Humanin protects cells against apoptosis, oxidative stress and amyloid toxicity, acting through STAT3 signalling, Bax inhibition and interaction with IGFBP-3.[2]
What it does not have is any human interventional data. Circulating humanin declines with age and correlates with markers of healthy ageing in observational work — including in the offspring of centenarians — but no trial has administered it to a person.[3] Everything in the community is extrapolation from cell culture and rodent models.
Observational association, not intervention
Higher circulating humanin correlates with longevity markers. That is a correlation in people who were already going to live longer, and it is exactly the kind of finding that does not license the inference that raising it exogenously changes anything.
// Mechanism of action
Anti-apoptotic signalling. Humanin binds a receptor complex and activates STAT3 signalling, and interacts with pro-apoptotic Bax to prevent its mitochondrial translocation — blocking the intrinsic apoptosis pathway.
IGFBP-3 interaction. Binds insulin-like growth factor binding protein 3, modulating IGF-1 availability. This is the connection to the growth-hormone axis and to the longevity literature around reduced IGF-1 signalling.
Protection against amyloid toxicity. The property it was discovered for — protecting neurons against amyloid-beta-induced death in culture.
Metabolic effects. Reported improvements in insulin sensitivity and glucose handling in rodent models, overlapping with the MOTS-c literature.
HNG analogue. A single serine-to-glycine substitution at position 14 produces an analogue reported to be substantially more potent than native humanin, and much of the pre-clinical work uses it rather than the native sequence.
01 Reported benefits
Effects that have been reported. A study-tier entry means a result was published — not that the effect is established, reproducible, or transferable from a rodent to a person.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Broad cytoprotection against apoptosis and oxidative stress [2]
Demonstrated across cardiac, neuronal, endothelial and beta-cell models via STAT3 activation and Bax inhibition.
Circulating levels decline with age [3]
Observed in humans and animals, with higher levels reported in the offspring of centenarians and in long-lived mouse models.
Improved insulin sensitivity in rodent models [2]
Reported alongside the broader metabolic effects of the mitochondrial-derived peptide family.
No human interventional study exists
No trial has administered humanin or HNG to a human at any dose.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Neuroprotection and cognitive preservation in humans
The primary use case, extrapolated from cell culture and the discovery context. There is no human data of any kind.
Cardioprotection
From rodent ischaemia-reperfusion work. Untested in humans.
Healthspan extension
Rests on the age-decline observation plus the centenarian-offspring correlation. Restoring a declining signal is not automatically beneficial, and this inference chain is long.
Protection of ovarian granulosa cells in PCOS
Granulosa cells in PCOS show increased apoptosis and metabolic stress, and humanin is anti-apoptotic via STAT3 and Bax inhibition. The chain from cytoprotection in neurons to improved ovulation runs through four untested assumptions — and blocking apoptosis in an ovary where follicular atresia is normal function may not point the way it is assumed to.
Complementary to MOTS-c
Both mitochondrial-derived peptides acting through different pathways — MOTS-c on AMPK, humanin on apoptosis and STAT3. The stack rationale is grouping rather than demonstrated interaction.
Concern: anti-apoptotic signalling
Apoptosis is how damaged and pre-malignant cells are removed. A systemically administered anti-apoptotic signal is, in principle, the opposite of what tumour suppression requires. Unstudied and worth naming.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Very little community experience
Humanin is expensive, rarely stocked and infrequently used. The anecdotal base is correspondingly thin, and thin honestly rather than through under-reporting.
Reported mental clarity and energy
Occasionally reported, typically alongside several other compounds.
No perceptible effect
The more common report, unsurprising for a cytoprotective signal with no acute pharmacology.
02 Adverse effects & risks
Adverse effects, contraindications and unknowns. The grey-market tier is where under-reporting is worst: uncontrolled use produces no systematic safety surveillance at all, so absence of a reported harm is not evidence of safety.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
No human safety data
No toxicology, pharmacokinetics or adverse-event data in humans. This is total absence, not thin evidence.
No notable toxicity in rodent studies [2]
Animal work reports tolerability at effective doses over study durations.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Anti-apoptotic effects in unwanted cells
Blocking programmed cell death systemically has an obvious theoretical downside for cells that should be dying.
IGF axis modulation
IGFBP-3 interaction alters IGF-1 availability, with unclear direction and consequences in a healthy adult.
Unknown effects of chronic MDP signalling
Sustained pharmacological manipulation of a stress-responsive mitochondrial signal has no characterisation.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Few reports of any kind
Reflecting very low usage volume rather than a demonstrated safety profile.
03 Dosing ranges
Figures below are documented, not recommended. Study ranges come from published protocols in the stated model; grey-market ranges are what the research community reports using and carry no safety validation of any kind.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Rodent dosing does not convert [2]
Animal work uses weight-normalised intraperitoneal or intracerebroventricular dosing, often with the HNG analogue. No validated human conversion exists.
No human dose established
Every figure in circulation is vendor suggestion.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Confirm which form you have
Native humanin and the HNG analogue differ substantially in potency, and much pre-clinical work uses HNG.
Short courses given the anti-apoptotic mechanism
If the theoretical concern is blocked cell turnover, intermittent exposure is the risk-minimising position.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
5–10 mg weekly, subcutaneous
A commonly cited community range, with no basis beyond vendor guidance.
1–2 mg daily
An alternative circulating pattern.
| Approach | Dose | Frequency | Notes |
|---|---|---|---|
| Weekly | 5 – 10 mg | Once weekly | Common vendor suggestion |
| Daily | 1 – 2 mg | Daily | Alternative pattern |
04 Synergy & interactions
Combination effects. Almost no peptide combination has been studied as a combination in humans; stack logic is overwhelmingly mechanistic inference and community practice. Each linked compound has its own page.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
No combination studies exist
None.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
With MOTS-c
Two mitochondrial-derived peptides on different pathways. Grouped together in the 15-Compound Matrix mitochondrial pillar.
With SS-31
Structural mitochondrial repair alongside cytoprotective signalling. Plausible framing, no data.
Tension with GH secretagogues
IGFBP-3 interaction modulates IGF-1 availability, while GH secretagogues aim to raise it. The direction of the interaction is unclear and nobody has looked.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Mitochondrial pillar of the 15-Compound Matrix
Listed with MOTS-c, NAD⁺ and Epitalon.
05 Protocols
Whole schedules — dosing, titration, cycle length, and off-time — as documented in trials, as proposed from mechanism, and as circulated in the research community. Reproduced for study and comparison only.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
No human protocol exists
No registered trial of any kind.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
There is no defensible protocol to construct
With no human pharmacokinetics, no human dose and no human safety data, any schedule is arbitrary. That is worth stating plainly rather than filling the space.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
15-Compound Matrix — Q1 mitochondrial priming
Grouped in the mitochondrial bioenergetics and longevity matrix.
Not part of the Gold Standard Protocol
The thirteen-compound protocol does not include it.
05b Condition-specific interest
Humanin was discovered in an unusual way — by screening for what protected surviving neurones in an Alzheimer brain — and the finding was that a mitochondrial gene encoded a peptide that blocked amyloid toxicity. That origin story is the most interesting thing here, and it has not translated into anything a person can use.
No approval, no trial
Humanin has no controlled human trial for any indication. The evidence is cell culture, animal models, and human observational work associating circulating levels with age, metabolic status and disease. It is not approved anywhere.
Theorized — the discovery context, still preclinical
Alzheimer disease and neuroprotection
Pathophysiology
Alzheimer disease involves amyloid-beta accumulation, tau pathology and neuronal loss. Why some neurones survive while neighbouring ones die is a real and unanswered question.
Mechanistic rationale
Humanin was identified from surviving neurones in an Alzheimer brain and shown to protect cells against amyloid-beta toxicity in culture, acting through anti-apoptotic signalling and a distinct receptor complex. That is one of the more genuinely interesting preclinical stories in this library. Two decades later there is still nothing human, in a field where a long list of mechanistically compelling candidates has failed at trial.
Community reports
Used in cognitive and longevity contexts. Cognitive self-assessment is unreliable, and the timescale over which dementia risk would change is far longer than anyone assesses.
Components carrying the argument: Anti-apoptotic signalling, amyloid toxicity protection
Theorized — animal plus human association
Insulin sensitivity and metabolic health
Pathophysiology
Insulin resistance precedes type 2 diabetes by years and is driven by lipid accumulation in muscle and liver alongside inflammatory signalling.
Mechanistic rationale
Humanin improves insulin sensitivity in rodent models, and circulating levels are associated with metabolic status in human observational work. The interpretation problem is the same as for MOTS-c: an association can mean the peptide protects, or that healthier mitochondria produce more of it. Only an intervention trial separates those, and none exists.
Community reports
Used for metabolic purposes, generally alongside other changes.
Components carrying the argument: Mitochondrial-derived metabolic signalling
Theorized — specific, and still cell-level
Granulosa cell protection in PCOS
Pathophysiology
Mitochondrial dysfunction and increased apoptosis in ovarian granulosa cells are documented in PCOS and are implicated in impaired follicular development and oocyte quality.
Mechanistic rationale
Humanin is anti-apoptotic and mitochondria-protective, so protecting granulosa cells is a specific and coherent proposal rather than a generic one — which distinguishes it from most PCOS claims in this library. It remains a cell-level rationale with no PCOS study behind it.
Community reports
Discussed in fertility-focused PCOS contexts.
Components carrying the argument: Anti-apoptotic action in granulosa cells
Actionable
The anti-apoptotic tension
Pathophysiology
Apoptosis is how the body removes damaged and potentially dangerous cells. Evasion of apoptosis is one of the defining hallmarks of cancer.
Mechanistic rationale
A systemically administered anti-apoptotic agent is asking damaged cells not to die. That is desirable in a neurone worth saving and undesirable in a cell that has acquired mutations. The same tension appears in different form on the Epitalon page with telomerase, and it is the recurring shape of the longevity-compound problem: the mechanisms that keep cells alive are the mechanisms tumours exploit. No human data exists in either direction.
Community reports
Not raised in community discussion.
Components carrying the argument: Anti-apoptotic signalling — the mechanism, cutting both ways
Theorized — animal, broad
Cardiovascular and ischaemic protection
Pathophysiology
Ischaemia-reperfusion injury involves mitochondrial permeability transition and apoptotic cell death in tissue that has been transiently deprived of perfusion.
Mechanistic rationale
Cardioprotective effects are reported in animal models of infarction and reperfusion. The same caution applies as for SS-31, whose broad animal protection record was followed by three missed primary endpoints in human trials.
Community reports
Cited in longevity contexts on the animal literature.
Components carrying the argument: Mitochondrial protection, anti-apoptosis
Theorized — observational, and interesting
Longevity and the centenarian association
Pathophysiology
Circulating humanin declines with age in humans, and higher levels have been associated with longevity in some observational work including in offspring of long-lived individuals.
Mechanistic rationale
It is a real and repeatedly observed association, and it is the reason humanin appears in longevity protocols. Declining with age is a property shared by a very large number of molecules, most of which are consequences of ageing rather than causes of it — and restoring a marker is not the same as reversing what produced the decline.
Community reports
A staple of longevity stacking, generally alongside MOTS-c and NAD+ precursors.
Components carrying the argument: Mitochondrial-derived peptide signalling
| Claim | Evidence | The thing to know |
|---|---|---|
| Neuroprotection / Alzheimer | Cell + animal | Compelling origin; nothing human in two decades |
| Insulin sensitivity | Animal + association | Marker or cause? No intervention trial |
| PCOS granulosa cells | Cell-level | Specific rationale, no PCOS study |
| Anti-apoptotic action | Established | Asks damaged cells not to die |
| Cardioprotection | Animal | See SS-31 — broad animal data, three trial misses |
| Longevity association | Observational | Declining with age is common and usually a consequence |
What actually has evidence for these conditions
For dementia risk: the evidenced list is unfashionable and consistent — treating midlife hypertension, correcting hearing loss, physical activity, sleep, glycaemic control, social and cognitive engagement, not smoking. The FINGER multidomain trial is the best-supported prevention model. For established Alzheimer disease: cholinesterase inhibitors, memantine, and the anti-amyloid monoclonals with their modest effect and real ARIA risk.
For insulin resistance: metformin, resistance and aerobic training, dietary change, sleep, and the incretin class where weight is central.
For PCOS: metformin, combined hormonal contraceptives, letrozole for ovulation induction, inositol. For oocyte quality specifically, the interventions with evidence are weight optimisation, glycaemic control and specialist fertility care.
06 Handling, reconstitution & storage
Physical-chemistry reference for laboratory handling of the lyophilised material. Reproduced so that stability and concentration mathematics can be studied — see the calculator for the arithmetic and the reconstitution guide for sterile technique.
Reconstitution
Supplied lyophilised, commonly 5 mg per vial. Reconstituted with bacteriostatic water.
Storage
Lyophilised: −20 °C. Reconstituted: 2–8 °C.
Common vial sizes
Commonly 5 mg lyophilised vials.
Stability notes
Confirm whether the product is native humanin or the HNG analogue — the certificate of analysis, if supplied, should state the sequence.
07 Legal & regulatory status
Regulatory status changes and differs by country. This is a summary for orientation, not legal advice — check your own jurisdiction.
Not approved anywhere and never studied in humans. Humanin is a research chemical with a genuine and interesting molecular-biology literature and no translational human evidence at all.
Regulatory and trial claims re-checked against primary sources on 16 August 2026. Checked: no approvals, no registered interventional human programme. Approvals, trial readouts and compounding decisions move faster than anything else on this page — a date here means someone looked, not that nothing has changed since.
Anti-doping
Athletes subject to WADA, USADA, UKAD, NCAA or military testing should assume any peptide is prohibited unless they have verified otherwise against the current WADA Prohibited List. Several classes here (growth-hormone secretagogues, TB-4 analogues, metabolic modulators) are explicitly named. Check the current list — it is republished annually.
§ Sources & further reading
Links resolve to PubMed records, trial registries, publisher pages or primary documents. Where a body of work rather than a single paper is cited, the link opens a PubMed query so the full result set — including newer papers than this page — can be reviewed. Verify every claim against the primary source before relying on it.
- Hashimoto Y, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer disease genes and Abeta. PNAS. 2001. (humanin discovery)In vitro / cell study
- PubMed: humanin — cytoprotection, STAT3, IGFBP-3 and metabolic effects (live query)Database or literature search
- PubMed: circulating humanin, ageing and longevity cohorts (live query)Database or literature search
Reminder
For educational and research reference only. Nothing on this site is medical advice, a recommendation, or an instruction to administer any substance to a human being. Every figure on this page is a record of what has been reported, not a recommendation. Full disclaimer.