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Longevity

Humanin

Gray market

Checked · 23 sources · 13 corrections on this page · No vendors · No affiliates · No one buys a word of it

0 human trials published

Preclinical · cell and rodent work · Gong 2014

Gray market · No FDA ruling — not on any list

Sold as a research chemical.

Bottom line

Twenty years of cell and rodent work (Gong et al., 2014), and no human trial of taking it, not even a phase 1 (ClinicalTrials.gov).

Also called
  • HN
  • Rattin (rat homolog)
  • HNG (S14G analog — ~1000× potency)
  • [Gly14]-humanin
  • encoded in the mitochondrial 16S rRNA ORF
Category
Peptide — Mitochondrial-Derived Peptide (MDP)
Class
Mitochondrial-derived peptide (MDP)
Length
24 amino acids
Molecular Weight
~2,687 Da
Genomic Origin
Mitochondrial 16S rRNA ORF
Discovery
Hashimoto et al. 2001 (PNAS)
Route (studied)
Into the brain (rats) · no human study
Route (sold)
SubQ vials (research chemical)
FDA Status
Not approved; research only
Human Trials
Observational only (endogenous levels)
Related MDPs
MOTS-c, SHLP1-6
Cost & Access
Research-only

Also for longevity

The other four questions

What does it do? In cells and rodents it blocked cell death: in neurons exposed to Alzheimer’s-linked genes and amyloid (Hashimoto et al., 2001), in mouse hearts after ischaemia (Muzumdar et al., 2010) and in the vessel lining of mice with atherosclerosis (Oh et al., 2011). It binds the cell-death protein Bax (Guo et al., 2003) and acts through a cytokine-receptor complex (Hashimoto et al., 2009).
Who uses it? Mitochondrial-biology and longevity labs. A small self-experimenter community on off-label supply. Not available through compounding pharmacies.
Does the evidence hold up? Preclinical only (Gong et al., 2014). In people, plasma humanin rose with age, highest in centenarians (Conte et al., 2019), and was lower in Alzheimer’s disease but not in type 2 diabetes (Conte et al., 2021). No trial has given humanin to people (ClinicalTrials.gov).
Bottom line? Twenty years of cell and rodent work (Gong et al., 2014), and no human trial of taking it, not even a phase 1 (ClinicalTrials.gov).

Dosing from the Literature

Published for longevity: doses in mouse and rat studies only (Tajima et al., 2005; Muzumdar et al., 2010). Not published: any human trial of taking humanin.

No human dose of humanin or its analogs has been studied. The rows give the animal studies; community figures are not reproduced, because no source read for this page documents them.

Study or formDoseRoute and scheduleNotes
Community HNG (S14G)Not documented by any source read—HNG rather than native humanin is the de facto community form given ~1000× potency.
Mice, amyloid memory model (Tajima et al., 2005)S14G-humanin, 50 pmol or moreInto the brain ventriclesPrevented amyloid-induced memory impairment
Mice, heart ischaemia (Muzumdar et al., 2010)HNG, dose-rangingIntraperitoneal, 1 hour before or at reperfusionInfarct size fell with dose
Mice, atherosclerosis (Oh et al., 2011)HNGF6A analogIntraperitoneal, daily for 16 weeksLess endothelial dysfunction and smaller plaques
Rats, insulin action (Muzumdar et al., 2009)Humanin; analogs IVContinuous infusion into the brain ventricles; IV infusions of analogsInsulin sensitivity improved
Dosing Disclaimer

No human dose of humanin has been studied; the rows are animal studies, not a dosing guide. Consult a licensed healthcare provider.

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What It Is

Humanin is a 24-amino-acid peptide with the sequence MAPRGFSCLLLLTSEIDLPVKRRA. It was first described by Yuichi Hashimoto and colleagues in 2001 (Proc Natl Acad Sci USA; PMID 11371646) while screening a complementary DNA library from the occipital cortex of an Alzheimer's disease brain — specifically, from neurons that had survived the characteristic amyloid-β and neurofibrillary tangle pathology of the disease. The peptide was functionally isolated for its ability to protect neuronal cell lines from toxicity induced by familial Alzheimer's disease mutations in amyloid precursor protein and presenilin. That original publication defined both the peptide and the functional hypothesis: humanin is an endogenous cytoprotective (cell-protecting) signal that may be upregulated in stressed neurons.

The defining and most unusual feature of humanin is its genomic origin. The open reading frame encoding humanin lies within the mitochondrial 16S ribosomal RNA gene — not in the nuclear genome. Humanin is transcribed from the mitochondrial genome, translated by either mitochondrial or cytoplasmic ribosomes (the question is still debated), and secreted into the cytoplasm and circulation. Nuclear pseudogenes of humanin also exist and may contribute to expression. This makes humanin the first recognized member of a broader class now called mitochondrial-derived peptides (MDPs) — a group that includes MOTS-c (encoded in the 12S rRNA) and the SHLP1-6 family (encoded in the 16S rRNA). MDPs are retrograde mitochondrial-to-cell signals that communicate mitochondrial functional status to the rest of the organism (Lee et al., Trends Endocrinol Metab 2013; PMID 23402768).

Native humanin is biologically active but modest in potency. The community and research standard is the S14G substitution analog — known as HNG or [Gly14]-humanin — which has approximately 1000-fold greater activity than native humanin in standard neuroprotection assays (Hashimoto et al., J Neurosci 2001; PMID 11717357). HNG is the version used in the majority of mechanistic preclinical research and in essentially all community biohacking contexts. The difference in potency comes from increased metabolic stability and altered receptor-binding kinetics conferred by the single glycine-for-serine substitution at position 14.

Circulating humanin has been measured in human plasma using validated ELISA and mass-spectrometry assays. In one case-control series, plasma humanin correlated positively with age in healthy subjects and was lower in Alzheimer's disease but not in type 2 diabetes (Conte et al., GeroScience 2021; PMID 33131010). No controlled human clinical trial of exogenous humanin has been reported, and the community use that has emerged is substantially ahead of the human evidence base.

Mechanism of Action

Humanin binds at least three partners in the studies cited here: a cytokine-receptor complex on the cell surface, the cell-death protein Bax, and IGFBP-3 (Hashimoto et al., 2009; Guo et al., 2003; Ikonen et al., 2003).

  • Receptor complex: CNTFR α / WSX-1 / gp130 — gp130 was essential for humanin’s neuroprotection, and CNTFR α and WSX-1 took part in its binding to neurons (Hashimoto et al., Mol Biol Cell 2009; PMID 19386761).
  • STAT3 — STAT3 activation was essential for its neuroprotection in cells (Hashimoto et al., 2009), and in rats its central effect on insulin action depended on hypothalamic STAT3 (Muzumdar et al., 2009).
  • BAX binding and mitochondrial-apoptosis inhibition — Humanin binds Bax and prevents its move from the cytosol to mitochondria, and blocked cytochrome c release in vitro (Guo et al., Nature 2003; PMID 12732850).
  • IGFBP-3 binding — Humanin binds IGFBP-3 with high affinity and blocked IGFBP-3-induced apoptosis; it did not compete with IGF-I for IGFBP-3 (Ikonen et al., PNAS 2003; PMID 14561895).
  • Insulin action (rats) — Humanin infused into the brain improved insulin sensitivity, and IV analogs reproduced the effect (Muzumdar et al., PLoS One 2009; PMID 19623253). A 2017 review lists less weight gain and visceral fat and more glucose-stimulated insulin release among its metabolic effects in animals (Kim et al., 2017).
  • Endothelial and vascular protection — Humanin activates eNOS and reduces oxidative stress in vascular endothelium (the lining of blood vessels), attenuating atherosclerosis progression in ApoE-knockout mouse models (Oh et al., Atherosclerosis 2011; PMID 21763658).
  • Mitochondrial retrograde signaling — The broader conceptual role of humanin (shared with MOTS-c and SHLPs) is as a retrograde signal from mitochondria to the cell nucleus and to distant tissues, communicating mitochondrial stress status and coordinating organism-level metabolic and stress responses (Lee et al., Trends Endocrinol Metab 2013; PMID 23402768).

What the Research Shows

The humanin evidence base spans cell-culture mechanism work, rodent disease-model efficacy studies, and observational human cohort measurements. No human interventional clinical trials have been completed or registered.

  • Discovery and Alzheimer's cytoprotection (Hashimoto et al., PNAS 2001; PMID 11371646) — The seminal discovery paper. Identified humanin from AD brain cDNA library; demonstrated rescue of neuronal cells from familial AD mutation toxicity. Defined the peptide and the therapeutic hypothesis.
  • HNG potency characterization (Hashimoto et al., J Neurosci 2001; PMID 11717357) — Established HNG (S14G analog) as approximately 1000-fold more potent than native humanin. The reference analog for most subsequent mechanism and preclinical work.
  • BAX-binding mechanism (Guo et al., Nature 2003; PMID 12732850) — Identified direct humanin–BAX binding as a molecular mechanism of intrinsic-apoptosis inhibition. A structural mechanism rare among bioactive peptides.
  • IGFBP-3 interaction (Ikonen et al., PNAS 2003; PMID 14561895) — Biochemical characterization of humanin–IGFBP-3 binding.
  • Amyloid-β-induced memory impairment (Tajima et al., J Neurosci Res 2005; PMID 15678515) — Intracerebroventricular S14G-humanin at 50 pmol or more prevented impairment of short-term and spatial working memory caused by amyloid-β 25-35 in mice on the Y-maze test; a neuroprotection-defective mutant did not.
  • Stroke (MCAO) protection (Xu et al., 2006; PMID 16960089) — In mice with a 75-minute middle cerebral artery occlusion, HNG given into the brain 30 minutes beforehand cut infarct volume from 56% to 26%; given after the occlusion, or into the abdomen beforehand, it also reduced infarct volume and improved neurological function.
  • Cardioprotection — ischemia/reperfusion (Muzumdar et al., ATVB 2010; PMID 20651283) — Humanin attenuated myocardial ischemia-reperfusion injury in mice; reduced infarct size and preserved left ventricular function.
  • Metabolic — insulin sensitization (Muzumdar et al., PLoS One 2009; PMID 19623253) — Intracerebroventricular HNG improved peripheral insulin sensitivity in rats through hypothalamic-hepatic signaling; reduced hepatic glucose output.
  • Atherosclerosis protection (Oh et al., Atherosclerosis 2011; PMID 21763658) — HNG attenuated atherosclerotic plaque formation in ApoE-knockout mice; mechanism attributed to anti-oxidative and anti-inflammatory endothelial effects.
  • MOTS-c and MDP family (Lee et al., Cell Metab 2015; PMID 25738459) — Broader context paper establishing MOTS-c as a second mitochondrial-derived peptide with exercise-mimetic metabolic effects; positions humanin within a growing MDP class.
  • No registered human interventional clinical trial — A ClinicalTrials.gov search finds no trial that gives humanin or an analog (October 4, 2026); its interventional records measure humanin as an outcome. All human data are observational, measuring endogenous humanin in relation to age, disease, and longevity.
Research Limitations

Humanin has no human interventional clinical trial data. All evidence is from cell culture, rodent disease models, and human observational cohorts measuring endogenous humanin levels. Dose, route, safety profile, and clinical efficacy of exogenous humanin / HNG in humans are unknown. Long-term consequences of administering an anti-apoptotic, broadly cytoprotective peptide — with theoretical concerns in the setting of pre-existing malignancy — have not been characterized. Community use is substantially ahead of the human evidence base.

Human Data

Human data on humanin is limited to observational cohort measurements of endogenous levels and correlational work linking those levels to age, disease, and longevity outcomes. No interventional clinical trial of exogenous humanin has been published.

  • Plasma humanin in disease versus healthy aging (Conte et al., GeroScience 2021; PMID 33131010) — Case-control comparison of plasma mitokines: humanin correlated positively with age in healthy subjects, and was lower in Alzheimer's disease but not in type 2 diabetes.
  • Cognitive aging (Yen et al., 2018; PMID 30242290) — A variant in the humanin-coding region of mitochondrial DNA (rs2854128) that lowers circulating humanin was associated with faster cognitive aging in a nationally representative cohort of older adults. Correlational, not interventional.
  • Type 2 diabetes — In the case-control series, plasma humanin was not lower in type 2 diabetes (Conte et al., 2021).
  • Exercise (Woodhead et al., 2020; PMID 32271093) — In 10 young untrained men, a bout of high-intensity interval cycling raised humanin in muscle and plasma; two weeks of such training trended toward lower resting plasma levels.
  • No registered interventional clinical trial — The gap between "this peptide is interesting in cohorts" and "this peptide is effective when administered exogenously" is the central unknown for humanin.

Reconstitution & Storage

Sellers list humanin and HNG as freeze-dried powder in milligram vials. No human dose has been studied, so no dose-volume table is given; the calculator does the arithmetic for any vial.

  • Identity verification — Whether a supplier product is native humanin or HNG (S14G analog) matters — potency differs ~1000-fold.

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Side Effects & Risks

Important

No trial has given humanin or its analogs to people (ClinicalTrials.gov), so nothing is known of its side effects in people. Consult a licensed healthcare provider.

  • Unknown human safety profile — The evidence is cell and animal work (Gong et al., 2014); no human safety data exist.
  • Cell-death blocking — Humanin blocks Bax-driven cell death (Guo et al., 2003). Whether that could also protect abnormal cells has not been studied in any source read for this page.
  • IGFBP-3 — It binds IGFBP-3 (Ikonen et al., 2003); no study has looked at what giving it does to the IGF system in people.
  • Drug interactions — Not studied.
  • What is in a vial — Humanin and HNG are sold online as research chemicals; no analysis of such products appears in the documents read for this page.
  • WADA status — Not named on the Prohibited List, but prohibited at all times under S0, non-approved substances, because no government has approved it for human therapeutic use (WADA Prohibited List 2026).

Bloodwork & Monitoring

No monitoring guidance exists; no human trial has given humanin. What human studies measured:

  • Plasma humanin — By age, in 693 people aged 21 to 113 (Conte et al., 2019), and in type 2 diabetes and Alzheimer’s disease against healthy ageing (Conte et al., 2021).
  • Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

No published study tests humanin with another compound, and no document read for this page names who combines it with what.

Stacking this? Read the receipt →

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Legal Status

Current Status — April 2026

Humanin and its analogs (including HNG / [Gly14]-humanin) are not FDA-approved for any indication. They are classified as research-phase peptides with no active IND applications or interventional clinical trials registered as of April 2026.

Humanin is not explicitly named on the FDA Category 2 Bulk Drug Substances list and was not among the 12 peptides FDA removed from it in April 2026 (FDA 503A categories list, April 22, 2026). As an endogenous 24-amino-acid peptide of mitochondrial origin without a commercial sponsor pursuing an approval pathway, humanin sits in an unregulated "research peptide" category outside the 503A / 503B compounding framework.

Humanin is not named on the WADA Prohibited List, but it is prohibited at all times under S0, non-approved substances, because no government has approved it for human therapeutic use (WADA Prohibited List 2026).

International regulatory status mirrors the US: no approved product, no interventional clinical trial program, available only through research-grade peptide suppliers.

Cost & Access

Humanin and HNG are available only through research-grade peptide suppliers for laboratory use. No approved pharmaceutical product exists in any jurisdiction.

U.S. compounding pharmacies cannot legally compound humanin under current FDA bulk-substance rules — it is not on an approved bulk list and there is no FDA-approved reference product. Research-chemical channels supply humanin / HNG as lyophilized powder in milligram-scale vials; quality and purity vary substantially.

Pricing and availability vary and are set by the seller. Kalios does not sell compounds.

References

  1. Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci USA. 2001;98(11):6336-6341. PMID: 11371646. (The seminal humanin discovery paper.)
  2. Hashimoto Y, Ito Y, Niikura T, Shao Z, Hata M, Oyama F, Nishimoto I. Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish mutant amyloid precursor protein. Biochem Biophys Res Commun. 2001;283(2):460-468. PMID: 11327724. (Early mechanism paper, HNG potency characterization.)
  3. Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003;423(6938):456-461. PMID: 12732850. (Humanin-BAX binding mechanism.)
  4. Ikonen M, Liu B, Hashimoto Y, Ma L, Lee KW, Niikura T, Nishimoto I, Cohen P. 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. 2003;100(22):13042-13047. PMID: 14561895.
  5. Hashimoto Y, Kurita M, Aiso S, Nishimoto I, Matsuoka M. Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130. Mol Biol Cell. 2009;20(12):2864-2873. PMID: 19386761. (Trimeric receptor complex characterization.)
  6. Muzumdar RH, Huffman DM, Atzmon G, Buettner C, Cobb LJ, Fishman S, Budagov T, Cui L, Einstein FH, Poduval A, Hwang D, Barzilai N, Cohen P. Humanin: a novel central regulator of peripheral insulin action. PLoS One. 2009;4(7):e6334. PMID: 19623253. (Hypothalamic-hepatic insulin-sensitization mechanism.)
  7. Muzumdar RH, Huffman DM, Calvert JW, Jha S, Weinberg Y, Cui L, Nemkal A, Atzmon G, Klein L, Gundewar S, Ji SY, Lavu M, Predmore BL, Lefer DJ. Acute humanin therapy attenuates myocardial ischemia and reperfusion injury in mice. Arterioscler Thromb Vasc Biol. 2010;30(10):1940-1948. PMID: 20651283. (Cardioprotection data.)
  8. Tajima H, Niikura T, Hashimoto Y, Ito Y, Kita Y, Terashita K, Yamazaki K, Koto A, Aiso S, Nishimoto I. Evidence for in vivo production of humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults. Neurosci Lett. 2002;324(3):227-231. PMID: 12009529. (In vivo humanin production.)
  9. Oh YK, Bachar AR, Zacharias DG, Kim SG, Wan J, Cobb LJ, Lerman LO, Cohen P, Lerman A. Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice. Atherosclerosis. 2011;219(1):65-73. PMID: 21763658.
  10. Lee C, Yen K, Cohen P. Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol Metab. 2013;24(5):222-228. PMID: 23402768. (Framing of humanin within MDP class.)
  11. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. PMID: 25738459. (MOTS-c — second MDP; expands the conceptual framework.)
  12. Kim SJ, Xiao J, Wan J, Cohen P, Yen K. Mitochondrially derived peptides as novel regulators of metabolism. J Physiol. 2017;595(21):6613-6621. PMID: 28574175.
  13. Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013;50(1):R11-R19. PMID: 23239898.
  14. Conte M, Ostan R, Fabbri C, Santoro A, Guidarelli G, Vitale G, Mari D, Sevini F, Capri M, Sandri M, Monti D, Franceschi C, Salvioli S. Human aging and longevity are characterized by high levels of mitokines. J Gerontol A Biol Sci Med Sci. 2019;74(5):600-607. PMID: 29955888. (Human observational: mitokines and longevity.)
  15. Gong Z, Tas E, Muzumdar R. Humanin and age-related diseases: a new link? Front Endocrinol (Lausanne). 2014;5:210. PMID: 25538685.
  16. Nashine S, Cohen P, Chwa M, Lu S, Nesburn AB, Kuppermann BD, Kenney MC. Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage. Cell Death Dis. 2017;8(7):e2951. PMID: 28726777.
  17. Tajima H, Kawasumi M, Chiba T, Yamada M, Yamashita K, Nawa M, Kita Y, Kouyama K, Aiso S, Matsuoka M, Niikura T, Nishimoto I. A humanin derivative, S14G-HN, prevents amyloid-beta-induced memory impairment in mice. J Neurosci Res. 2005;79(5):714-723. PMID: 15678515.
  18. Conte M, Sabbatinelli J, Chiariello A, Martucci M, Santoro A, Monti D, Arcaro M, Galimberti D, Scarpini E, Bonfigli AR, Giuliani A, Olivieri F, Franceschi C, Salvioli S. Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer's disease in comparison with healthy aging. GeroScience. 2021;43(2):985-1001. PMID: 33131010.
  19. Xu X, Chua CC, Gao J, Hamdy RC, Chua BH. Humanin is a novel neuroprotective agent against stroke. Stroke. 2006;37(10):2613-2619. doi:10.1161/01.STR.0000242772.94277.1f. PMID: 16960089.
  20. Yen K, Wan J, Mehta HH, Miller B, Christensen A, Levine ME, et al. Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans. Sci Rep. 2018;8(1):14212. doi:10.1038/s41598-018-32616-7. PMID: 30242290.
  21. Woodhead JST, D'Souza RF, Hedges CP, Wan J, Berridge MV, Cameron-Smith D, et al. High-intensity interval exercise increases humanin, a mitochondrial encoded peptide, in the plasma and muscle of men. J Appl Physiol (1985). 2020;128(5):1346-1354. doi:10.1152/japplphysiol.00032.2020. PMID: 32271093.
  22. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)
  23. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Read October 3, 2026.

Also for longevity

Tested together in people

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Checked 18 Oct 2026