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Humanin24 residuesMAPRGFSCLLLLTSEIDLPVKRRAEach bubble = one amino acid. Size = residue mass. Color = chemical class.Also known as: HN, MT-RNR2, HNG (S14G-Humanin analog)
Circulating levels drop measurably with every decade of life. Humanin is a 24-amino acid peptide encoded directly in mitochondrial DNA, first isolated from surviving neurons in an Alzheimer's patient's brain back in 2001. No human clinical trial has been completed, and the cancer safety question remains open; two preclinical studies show the same anti-apoptotic mechanism that protects neurons also shields tumor cells. Longevity-focused biohackers pair it with MOTS-c in mitochondrial stacks, though dosing protocols are entirely extrapolated from rodent data and community self-experimentation.
Circulating humanin levels decline with age across every population studied so far. That single observation launched two decades of research into whether replacing this 24-amino acid mitochondrial-derived peptide (MDP) could slow aspects of aging. Nishimoto and colleagues first isolated humanin in 2001 from the occipital lobe of an Alzheimer's disease patient (CAS: not yet assigned; also known as HN, MT-RNR2-derived peptide). The peptide sits within the 16S ribosomal RNA gene of mitochondrial DNA, making it one of several bioactive molecules encoded outside the nuclear genome. MOTS-c belongs to the same family. The mechanism is multi-pronged. Humanin directly binds the pro-apoptotic protein BAX, blocking it from puncturing the mitochondrial outer membrane. It activates JAK/STAT3 signaling through a trimeric receptor complex (CNTFR, WSX-1, gp130). It also binds IGFBP-3, preventing IGF-1-independent apoptosis. The result across cell and animal models is broad cytoprotection; neurons, cardiac cells, retinal tissue, and pancreatic beta cells all benefit. A 2020 study in Aging [1] tracked HNG-treated mice and found better cognitive performance, improved metabolic markers, and reduced inflammatory signaling compared to controls. Insulin sensitivity improvements appeared consistently across rodent studies. The catch is real. Zero completed human clinical trials exist. All published dosing data comes from intraperitoneal injection of HNG (the S14G analog, roughly 1,000x more potent than native humanin) in mice and rats. Rat PK data from Muzumdar and colleagues [2] showed humanin undetectable in brain tissue after systemic injection. Two preclinical studies document humanin actively promoting tumor progression in triple-negative breast cancer (Scientific Reports 2020) and glioblastoma invasion (Cell Death and Disease 2024).
Humanin operates through three distinct signaling axes, each converging on a single outcome: cell survival. On the extracellular side, humanin binds a trimeric receptor complex composed of CNTFR, WSX-1, and gp130. This triggers JAK/STAT3 signaling, which upregulates anti-apoptotic gene expression. Humanin also engages formyl peptide receptors FPRL1 and FPRL2, activating ERK 1/2 phosphorylation. That pathway links to both neuroprotection and inflammation modulation. Inside the cell, the picture gets more specific. Humanin directly binds BAX, a pro-apoptotic BCL-2 family protein. By sequestering BAX, it prevents translocation to the mitochondrial outer membrane. No pore formation means no cytochrome c release, which shuts down the caspase cascade before it starts. Humanin also binds tBID, blocking the BAX/BID oligomerization that amplifies membrane permeabilization (Morris et al.)[3]. The third axis involves IGFBP-3. Humanin binds IGFBP-3 and prevents it from triggering its IGF-1-independent cell death program. Interestingly, this same binding accelerates humanin's plasma clearance; analogs like HNGF6A that skip IGFBP-3 binding circulate longer in rodent models. At the mitochondrial level, humanin localizes to lysosomal membranes and activates chaperone-mediated autophagy. It also triggers the PI3K/AKT pathway, promoting mitochondrial biogenesis and improving respiratory chain efficiency. The double-edged nature of all this is worth sitting with. Every pathway that protects a healthy neuron from apoptosis can just as easily protect a tumor cell.
Neuroprotective and anti-apoptotic in vitro and animal models; improves insulin sensitivity and metabolic markers in rodents; lifespan extension in C. elegans and mouse models. No completed human clinical trials as of April 2026. CNS penetration via systemic injection undetectable in rat PK data (PMC3776863), undermining neuroprotection claims for SC dosing. Two published studies document humanin as a pro-tumoral factor: TNBC tumor progression (Sci Reports 2020) and GBM invasion via integrin αV–TGFβ axis (Cell Death & Disease 2024). Virtually all mechanistic and efficacy data uses HNG (1,000x more potent analog), not native humanin.
Muzumdar et al. 2009/2013 (PMC3776863): PK and tissue distribution in rodents; Lee et al. 2020 (PMID 32575074): humanin as healthspan regulator in mice; Nishimoto et al. 2000 (original discovery from AD brain)
No human interventional trials completed. All dosing extrapolated from animal IP injection studies. Human PK (half-life, bioavailability, CNS penetration) entirely unknown. Most published research uses HNG, not native humanin: results cannot be directly translated. Cancer promotion documented in two distinct preclinical models. IGFBP-3 binding dynamics differ between species, making PK extrapolation unreliable.
Intellectually compelling longevity and neuroprotection peptide with very limited self-report data. Most users combine with MOTS-c in a "mitochondrial MDP" stack. High cost and half-life logistics limit adoption. No community consensus on effective dose or measurable cycle outcome.
Community interest mirrors scientific targets (neuroprotection, mitochondrial support, anti-aging) but the community largely lacks awareness of: (1) the 2024 Cell Death & Disease GBM invasion data (integrin αV–TGFβ axis: a new cancer mechanism distinct from anti-apoptosis), (2) rat PK data showing humanin undetectable in brain tissue after systemic injection, and (3) the native vs. HNG potency gap creating ~1,000x dosing ambiguity at the vendor level.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 1mg | EOD |
| Moderate | 3mg | 3x/week |
| Aggressive | 5mg | 3x/week |
Confirm which form you have before doing anything else. Most vendors sell HNG (S14G-Humanin), which is roughly 1,000x more potent than native humanin. Using HNG at milligram doses would be a massive overdose. Ask the vendor in writing: native humanin or HNG? Get it confirmed before opening the vial. For a 5 mg native humanin vial reconstituted with 2 mL bacteriostatic water, concentration is 2.5 mg/mL. On a U100 insulin syringe, 1 mg equals 0.4 mL, which is 40 units. A 3 mg dose comes to 1.2 mL (120 units); that's a large SC volume, so consider reconstituting 5 mg in 1 mL BAC water instead (5 mg/mL, making 3 mg equal to 60 units). Each 5 mg vial provides five doses at 1 mg or roughly 1.7 doses at 3 mg. A 10-week moderate cycle (3 mg three times weekly, 90 mg total) requires about 18 vials. At $75.99 per vial, that's around $1,368 before shipping. Plan your reconstitution timing carefully; reconstituted vials only last 21 to 30 days refrigerated.
No established cycling protocol exists for humanin in humans. These ranges are extrapolated from general peptide cycling practices and community reports. Periodic breaks are recommended given the absence of long-term safety data. Monitor for any unusual symptoms throughout use.
No receptor desensitization or antibody formation data exists for humanin. Cycling is based on the precautionary principle given: (1) absent long-term human safety data, (2) documented pro-tumoral activity in two preclinical cancer models (TNBC and GBM), and (3) the anti-apoptotic mechanism that theoretically could protect occult tumor cells with sustained use. The 10-week on / 5-week off schedule is community-extrapolated, not evidence-based.
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Expected: No validated human outcome data. Animal models suggest potential insulin sensitivity and inflammatory marker improvements over 4–12 weeks of consistent dosing. Cognitive or neuroprotective effects from peripheral SC dosing have no established CNS mechanism.
Monitor: Fasting glucose at baseline and week 6. Cancer screening before starting: anti-apoptotic mechanism is a hard contraindication with any cancer history.
Reconstitute the 5 mg vial by adding 2 mL bacteriostatic water slowly along the glass wall. Don't spray directly onto the powder. Swirl gently until fully dissolved. Never shake.
At 2 mL BAC water per 5 mg vial, concentration is 2.5 mg/mL. For a 1 mg dose, draw 40 units on a U100 insulin syringe (0.4 mL). For a 3 mg dose, draw 120 units (1.2 mL), or reconstitute with 1 mL BAC water for a 5 mg/mL concentration and draw 60 units instead.
Preferred areas: lower abdomen (avoiding a 2-inch radius around the navel) or upper outer thigh. Rotate sites each injection.
Pinch the skin and insert a 29 to 31 gauge insulin syringe at a 45-degree angle. Inject slowly. Hold for 5 seconds before withdrawing.
Administer in the morning or early afternoon on an empty stomach. The beginner protocol is 1 mg every other day; the moderate protocol calls for 3 mg three times per week (Mon/Wed/Fri).
Use within 21 to 30 days. Never freeze reconstituted solution. Lyophilized vials store at minus 20 degrees Celsius or colder for 12 to 24 months.
No human intranasal dose established. Mouse studies used intranasal HNG over 3 months. No human dose equivalent derived.
Intranasal delivery may achieve CNS penetration that systemic injection cannot: rat PK data (PMC3776863) shows humanin undetectable in brain tissue after IP injection. Not commercially available as intranasal formulation. Some researchers have explored DIY nasal spray reconstitution, but this is non-standard and raises sterility concerns. Mechanistically superior to SC for CNS targets based on mouse data.
All animal efficacy data (2.5–4 mg/kg HNG, IP) used IP route. SC bioavailability relative to IP is unknown in humans.
IP injection is not a human self-administration route. Noted only to contextualize why all published animal dosing data is difficult to directly translate into human SC protocols.
Most frequently cited MDP combination in longevity community. MOTS-c acts primarily via AMPK on nuclear gene expression and metabolic regulation; humanin acts on apoptotic signaling (BAX inhibition, JAK/STAT3). Complementary targets within the mitochondrial-derived peptide family.
Humanin Mon/Wed/Fri SC; MOTS-c Tue/Thu SC
Additive mitochondrial membrane protection. SS-31 stabilizes cardiolipin on the inner mitochondrial membrane; humanin inhibits BAX-mediated outer membrane permeabilization. Complementary mechanisms. Note: SS-31 has human Phase 2 trial data; humanin has none.
Longevity protocol framing. Different mechanisms (humanin: apoptosis inhibition; Epithalon: telomerase activation/pineal regulation). Often cycled together in anti-aging stacks. Humanin carries documented cancer risk signal that Epithalon does not.
Anti-aging cytoprotective stack. GHK-Cu promotes tissue repair and antioxidant gene expression; humanin inhibits mitochondrial apoptosis. No known interaction concerns at community doses.
Humanin's anti-apoptotic mechanism (BAX inhibition, STAT3 activation) may protect cancer cells from chemotherapy-induced programmed death. Documented in GBM (Cell Death & Disease 2024: integrin αV–TGFβ axis) and TNBC (Sci Reports 2020). Risk of blunting therapeutic efficacy of any pro-apoptotic cancer treatment.
Do not combineHumanin binds IGFBP-3 and partially antagonizes the GH/IGF-1 signaling axis. Concurrent use may blunt intended GH/IGF-1 effects. Magnitude of antagonism in humans is unknown but mechanistically documented in animal models.
Humanin improves insulin sensitivity via hypothalamic STAT3 and β-cell mechanisms in animal models. Co-administration with insulin or sulfonylureas may increase hypoglycemia risk.
Therapies relying on apoptosis induction (senolytics such as navitoclax, dasatinib; BCL-2 inhibitors) may be mechanistically antagonized by humanin's BAX-inhibiting activity. Combined use not studied; antagonism is biologically plausible.
Pricing updated 2026-04-09
The cancer risk is the single biggest safety flag in humanin research, and it deserves front position. A 2020 study in Nature Scientific Reports showed humanin actively promoted tumor progression in triple-negative breast cancer mouse models. A 2024 paper in Cell Death and Disease documented a second, mechanistically distinct cancer pathway: humanin facilitated glioblastoma invasion via the integrin alphaV-TGFbeta axis. These aren't theoretical concerns extrapolated from mechanism. They're published experimental results. Humanin's core biological activity, inhibiting BAX-mediated apoptosis, is the same mechanism that would protect cancer cells from programmed death. Anyone with active cancer, a cancer history, or strong genetic predisposition (BRCA mutations, Lynch syndrome) should treat humanin as a hard contraindication. This isn't a gray area. Beyond cancer, there are growth and reproductive concerns from animal data. Sustained humanin overexpression has impaired growth and reproductive function in animal models, likely through its antagonistic relationship with the GH/IGF-1 axis. The clinical relevance to adult human dosing is unknown, but it's reason enough to keep humanin away from anyone under 18. Human side-effect data from actual clinical experience doesn't exist because no interventional trials have been completed. The total human evidence base for adverse effects is zero controlled participants. In animal studies at standard research doses, humanin has been tolerated without major reported adverse events. Mild injection-site reactions (redness, swelling at the subcutaneous site) are expected with any injectable peptide and typically resolve within 24 to 48 hours. Hypoglycemia risk increases if you're co-administering insulin or oral hypoglycemics. Humanin improves insulin sensitivity through hypothalamic STAT3 and beta-cell mechanisms in animal models. That combination benefit could push blood sugar too low. Pregnancy and breastfeeding are contraindicated. No reproductive safety data exists in any species at relevant doses. When to stop: any new or unexplained mass, tissue growth, or tumor symptoms. Signs of hypoglycemia. Persistent injection site reactions beyond 48 hours. Any new neurological symptoms given the completely unknown CNS pharmacology in humans. Discontinue and consult a physician.
Verify Humanin dosing and safety with a second opinion
Native vs. HNG mislabeling is an industry-wide issue: vendors do not consistently specify which form is supplied. HNG is ~1,000x more potent; receiving HNG labeled as native humanin while dosing at mg-level creates extreme overdose risk. Peptide Sciences (major quality-reference vendor) shut down operations in 2025-2026. No FDA oversight of research peptide isoform labeling. HPLC purity testing does not distinguish native humanin from HNG: mass spectrometry confirmation is required.
| Test | When | Target |
|---|---|---|
| Fasting glucose and fasting insulin | Baseline and week 6 | Fasting glucose 70–99 mg/dL; fasting insulin <10 µIU/mL |
| Age- and risk-appropriate cancer screening | Before initiating any humanin protocol | — |
| CBC (complete blood count) | Baseline | — |
| Liver function panel (ALT, AST, bilirubin) | Baseline | — |
Humanin improves insulin sensitivity via hypothalamic STAT3 and β-cell mechanisms in animal models. Risk of hypoglycemia increases with co-administered insulin or oral hypoglycemics.
Humanin promotes tumor progression in TNBC (Sci Reports 2020) and GBM invasion via integrin αV–TGFβ axis (Cell Death & Disease 2024). Cancer history or strong genetic predisposition (BRCA, Lynch syndrome, etc.) is a hard contraindication.
No humanin-specific hematologic signal known. Establishes baseline and identifies pre-existing conditions that may interact with anti-apoptotic activity.
No humanin-specific hepatotoxicity documented. Standard precautionary monitoring for any novel research peptide with no completed human safety trials.
Possible improvements in subjective energy and cognitive clarity based on anecdotal reports. No clinical data supports a specific onset timeline. This is an assessment period.
Potential metabolic improvements (insulin sensitivity, inflammatory markers) based on extrapolation from animal study timelines.
Cumulative effects on cellular protection and mitochondrial function may begin to manifest. Animal studies typically show measurable outcomes by this point.
Full effects on cellular protection may require sustained administration. Most animal studies run 4-12 weeks. Reassess and decide on continuation.
Weeks 1 to 2 (Assessment Period): No human onset data exists for humanin at any dose or route. Rodent pharmacokinetics show peak plasma concentration at roughly 10 minutes in mice (IP) and about 4 hours in rats (IP), with brain tissue levels undetectable after systemic injection (Muzumdar et al.)[2]. Some biohackers report mild subjective energy or cognitive clarity during the first two weeks. No objective data supports a specific onset; these effects may reflect placebo or co-administered peptides like MOTS-c or NAD+ precursors. Minor injection site redness is common and typically resolves within a day or two. Weeks 3 to 6 (Potential Metabolic Effects Window): Animal models using HNG at 2.5 to 4 mg/kg IP showed insulin sensitivity and inflammatory marker improvements by weeks 4 through 6. Those studies used intraperitoneal HNG, not subcutaneous native humanin at human-equivalent doses. Direct translation isn't supported. Community data is thin here; one documented self-experiment (1 mg twice daily for 15 days) noted subjective energy improvements, but no consistent pattern has emerged across protocols. Weeks 6 to 10 (Cumulative Cellular Protection Phase): Mouse HNG studies at 4 mg/kg twice weekly (IP) showed reduced visceral fat, improved lean mass, and better metabolic markers by weeks 8 through 12. No SC native humanin animal data at human-equivalent doses exists to anchor expectations. Most community protocols run 8 to 12 weeks before attempting any assessment. High cost (around $1,368 for a 10-week moderate cycle) likely drives significant dropout before cycle completion. Post-Cycle Weeks 11 to 15 (Off-Cycle Washout): No human washout data exists. Rodent PK suggests rapid clearance on the scale of minutes in mice, hours in rats. No rebound effects, tolerance, or receptor changes have been documented. Community reports indicate a return to pre-cycle subjective baseline with no discontinuation effects. No biomarker washout data is publicly available from any self-experiment.
No human onset timeline data. Rodent PK shows peak plasma at ~10 min (mice IP) or ~4 h (rats IP) with rapid clearance; brain tissue levels undetectable in rats after systemic injection. Human SC kinetics entirely unknown.
Some biohackers report mild subjective energy or cognitive clarity within the first 1–2 weeks. No objective data validates this; effect may be placebo or driven by co-administered peptides (MOTS-c, NAD+).
Animal models (HNG IP) show improvements in insulin sensitivity and inflammatory markers by weeks 4–6. Studies used IP injection of HNG at 2.5–4 mg/kg: not SC native humanin at human-equivalent doses. Direct translation is not supported.
Limited data. One documented anecdotal report (1 mg 2x/day × 15 days) noted subjective energy improvements. No consistent pattern across community protocols.
Mouse HNG studies (4 mg/kg 2x/week IP) showed reduced visceral fat and improved lean mass and metabolic markers by weeks 8–12. No SC native humanin animal data at human-equivalent doses exists to anchor expectations.
Most community protocols run 8–12 weeks before assessing results. No systematic outcome tracking found publicly. High cost likely drives significant dropout before cycle completion.
No human washout data. Rodent PK suggests rapid clearance (minutes in mice, hours in rats). No rebound pharmacology, tolerance, or receptor upregulation documented.
No community reports of discontinuation effects. Users report return to pre-cycle subjective baseline. No biomarker washout data available from any self-experiment.
Source: Muzumdar et al. 2009 (PMID 23836030): ~30 min half-life in mice (IP injection). Rats showed >4 hours. Human PK data is unavailable.
Loading the interactive decay curve.
Humanin is classified as a research-only peptide. It has no FDA approval, no IND application on record, and no completed human clinical trials. It is not a pharmaceutical drug and cannot be marketed for human consumption or therapeutic use. Research peptide vendors sell humanin (native or HNG analog) under "for research purposes only" labeling. No compounding pharmacy formulation exists. Purchase and possession for personal research is legal in the United States, though the regulatory environment around research peptides continues to shift. The closure of Peptide Sciences in 2025 to 2026 reduced supply chain options. Athletes should note that humanin's regulatory status under WADA has not been specifically addressed, but novel peptide hormones and their analogs generally fall under the S2 category (peptide hormones, growth factors, related substances) on the WADA Prohibited List. Competitive athletes should assume it is prohibited in and out of competition. This content is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Consult a qualified healthcare provider before using any research peptide.
Peptide Schedule Research TeamReviewed Apr 20268 Citations
