Humanin
HN · HNG (potent analog) · MT-RNR2 peptide
Cytoprotective mitochondrial-derived peptide; preclinical evidence with no human RCTs
Overview
Humanin is a small mitochondrial-derived peptide — encoded within the mitochondrial 16S rRNA (MT-RNR2) region rather than the nuclear genome — first discovered through its ability to protect neurons from amyloid-beta toxicity. That origin places it alongside MOTS-c in the emerging class of peptides the mitochondria appear to use to signal to the rest of the cell, and it has since been studied for cytoprotective, metabolic, and cardiovascular effects.
Mechanistically it is best characterized as a survival factor. It binds and sequesters the pro-apoptotic protein BAX to block programmed cell death, activates STAT3 signaling through a cell-surface receptor complex (FPRL1/FPR2 and the CNTFR–gp130–WSX-1 trimer), and has been linked to chaperone-mediated autophagy. Observational human work has connected higher endogenous humanin levels to longevity and lower levels to age-related disease, but that is correlational. A more potent engineered analog, HNG (in which serine-14 is replaced with glycine), is the form most often used in animal research because the native peptide's circulating half-life is only about thirty minutes.
There are no published human randomized trials of humanin as of 2026, so all dosing is extrapolated rather than validated. The most-cited animal protocol used HNG at 4 mg/kg intraperitoneally twice weekly in middle-aged mice; community research-use planning translates this loosely into subcutaneous milligram-range doses one to three times weekly over four-to-twelve-week cycles. These figures are summarized for research reference only and should not be read as an established protocol.
Key parameters
- Dose range
- Community-dependent, mg-range SC (no validated human dose)
- Frequency
- Roughly 1–3× weekly in cycles (community)
- Half-life
- Native peptide ~30 min; the HNG analog was engineered to last longer
- Route
- Subcutaneous
- Vial sizes
- 5 mg · 10 mg
- Regulatory status
- Not approved as a drug by any regulator; no FDA-approved human dose exists. Research use only.
Mechanism of action
BAX sequestration / anti-apoptotic signaling
Humanin binds the pro-apoptotic protein BAX and prevents its translocation to mitochondria, blunting the intrinsic (mitochondrial) apoptosis pathway and protecting stressed cells from death.
Receptor-mediated STAT3 / cytoprotection
It acts at a cell-surface receptor complex (FPRL1 and the CNTFR/gp130/WSX-1 trimeric receptor) to activate STAT3 signaling, which drives protective, anti-inflammatory, and metabolic gene programs in neurons and endothelium.
Mitochondrial-stress (mitokine) signaling
As a mitochondrial-encoded peptide, humanin is studied as a 'mitokine' that links mitochondrial status to whole-body stress responses, including improved insulin sensitivity and reduced oxidative damage in preclinical models.
Dosing protocol & phases
| Phase | Weeks | Dose | Notes |
|---|---|---|---|
| Community cycle (research-use) | 4–12 week cycles | mg-range subcutaneously, ~1–3× weekly | Extrapolated from animal HNG protocols; no validated human dose exists. Cycles are often followed by comparable off periods. |
| Reference animal protocol | Study duration | HNG 4 mg/kg intraperitoneally, twice weekly (mice) | The most-cited preclinical schedule, included for context only; not a human protocol. |
Reconstitution guide
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.
5 mg vial + 2 mL bacteriostatic water
Concentration2,500 mcg/mL · 2.5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 1,000 mcg | 0.4 mL | 40 |
| 2,500 mcg | 1 mL | 100 |
Standard mix from a 5 mg vial for research-use planning.
10 mg vial + 2 mL bacteriostatic water
Concentration5,000 mcg/mL · 5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 2,500 mcg | 0.5 mL | 50 |
| 5,000 mcg | 1 mL | 100 |
Higher-strength mix that keeps larger draws within a single syringe.
Reconstitution calculator
Pre-filled with Humanin's vial sizes. Adjust the water volume and target dose to see the exact draw, with warnings for doses that are hard to measure or won't fit a syringe.
At 2,500 micrograms per millilitre, a 1,000 microgram dose is 0.4 millilitres, or 40 units on a U-100 syringe, giving 5 doses per vial.
Supplies needed
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Recommended supply
Humanin — research vial
From our verified partner Dynotides, with a third-party certificate of analysis per batch.
Injection supplies
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Bacteriostatic water
Diluent for reconstituting lyophilized vials.
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Insulin syringes (U-100)
0.3–0.5 mL, 29–31 G for accurate small draws.
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Alcohol prep pads
Sterile swabs for the vial stopper and site.
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Sharps container
Safe disposal of used needles.
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Storage fridge
Keeps reconstituted vials at 2–8 °C.
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Insulated travel case
Cooled, TSA-friendly case for travel.
Missed-dose guidance
No approved-label guidance exists, as humanin is not an approved drug. On the cyclical community schedules described, a missed dose is simply resumed at the next planned administration rather than doubled.
Side effects & safety
| Category | Effect | Trial incidence |
|---|---|---|
| Injection site | Local reactions (redness, irritation)Anecdotal; no controlled human incidence data. | — |
| General | Mild fatigue, headache, or transient nauseaReported anecdotally in research-use contexts. | — |
| Theoretical | Cancer-surveillance concern from BAX inhibitionBecause humanin is anti-apoptotic, chronic exposure raises a theoretical worry about impaired clearance of abnormal cells; unquantified. | — |
| Metabolic | Possible glucose-handling shiftsGiven its metabolic activity, effects on glucose regulation are plausible and unstudied in humans. | — |
Clinical trials & evidence
Preclinical cytoprotection / metabolic studies
Preclinical (animal/cell)Varies (weeks to months) · Rodent models and cell lines
HNG and humanin reduced neuronal apoptosis, improved insulin sensitivity, and lessened cardiac and vascular damage in models; no human efficacy trials.
Trial identifier needs verification
Human observational (endogenous levels)
ObservationalN/A · Human cohorts
Higher circulating humanin has been associated with longevity markers and lower levels with age-related disease; correlational only, not interventional.
Trial identifier needs verification
Storage & handling
- Lyophilized
- Store lyophilized powder frozen (around −20 °C) for long-term storage, protected from light; brief refrigeration is acceptable short-term.
- Reconstituted
- Refrigerate the reconstituted solution at 2–8 °C and use within roughly 28 days; do not freeze.
Comparisons
| Vs. | Target | Half-life | Dosing | Efficacy | Status |
|---|---|---|---|---|---|
| MOTS-c | Mitochondrial-derived peptide (both) | ~30 min (native) vs not characterized | Community-dependent (both) | Both preclinical; humanin emphasized for cytoprotection, MOTS-c for metabolic/AMPK effects | Both not approved |
| SS-31 | Mitokine signaling vs inner-membrane cardiolipin stabilization | ~30 min (native) vs short | Community SC vs daily SC in trials | Humanin is preclinical; SS-31 has reached human trials | Both not approved |
Sources & references
- [1]Hashimoto Y et al. A rescue factor abolishing neuronal cell death by a wide spectrum of Alzheimer's disease genes and Abeta (identification of humanin). PNAS 2001. ↗ source
- [2]Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress, metabolism, and disease. Endocr Rev / reviews of humanin biology. ↗ source
Frequently asked questions
What is HNG?
HNG is an engineered, more potent analog of humanin carrying a single serine-to-glycine substitution at position 14. It is the form most preclinical studies actually use, because it is more stable and far more active than the native peptide, whose half-life is only about thirty minutes.
Is there a validated human dose for humanin?
No. There are no published human randomized trials, so the doses seen in research-use circles are extrapolated from animal HNG protocols rather than tested in people. They should be treated as unvalidated.
Why might its anti-apoptotic action be a double-edged sword?
Blocking programmed cell death protects healthy stressed cells, which is the therapeutic rationale, but the same mechanism could in principle interfere with the body's clearance of damaged or precancerous cells. This is a theoretical concern that has not been quantified in humans.
Related protocols
MOTS-c
Mitochondrial-derived peptide
Mitochondrial-derived peptide regulating metabolic homeostasis (preclinical)
SS-31
Elamipretide
40 mg/day SC; MMPOWER-3 Phase 3 missed its 6-minute-walk primary endpoint
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For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.