Skip to content

For Research & Educational Discussion Only. Not Medical Advice

BaselineForum

Humanin

Mitochondrial-derived peptide

Also known as HN, MT-RNR2, Rattin

A peptide encoded in mitochondrial DNA, of real scientific interest as a signaling molecule, with no interventional human trial of it as a therapy.

What doses have been studied? What each trial gave, with the population it was given to.

Guide updated Oct 22, 2026Literature checked Oct 21, 20262 curated studies30 literature recordsBaseline editorial

This entry is preclinical

There is no completed human trial reporting results for this compound. Everything below describes what has been observed in animals or in cell culture, and the transfer rate from those findings to humans is poor. Read the limitations on each study, not just the findings.

Overview

In shortA short peptide coded by your mitochondria rather than the DNA in the nucleus, which was genuinely surprising when described and remains the most interesting thing about it. It was found in surviving neurons from Alzheimer's brain tissue and studied since as a cell-protecting signal. Its use as a treatment runs well ahead of anything tested.

Humanin is a short peptide encoded within the mitochondrial genome rather than the nuclear one, which was a genuinely surprising finding when it was described and remains the most interesting thing about it. It was identified in surviving neurons from Alzheimer's brain tissue and has been studied since as a cytoprotective signaling molecule.

It belongs to a small family of mitochondrial-derived peptides that also includes MOTS-c, which this compendium covers separately. The research interest is real and largely mechanistic. Its use as an intervention runs well ahead of anything tested.

Mechanism

In shortIt is proposed to work through a receptor complex and, separately, by blocking proteins that trigger cell suicide. Levels in the blood fall with age, and that observation is the origin of most of the interest. It is also where the reasoning most often goes wrong: something declining with age does not establish that topping it back up reverses anything, and that has not been tested here.

Proposed to act through a receptor complex involving CNTFR, WSX-1 and gp130, and separately through interaction with pro-apoptotic proteins including BAX, suppressing apoptosis.

Circulating levels decline with age, and that observation is the origin of most of the interest in it. It is also where the reasoning most often goes wrong: something declining with age does not establish that restoring it reverses anything, and that inference has not been tested here.

Evidence

In shortLab and animal work. Cell and animal studies report protective effects in models of Alzheimer's, restricted blood flow and metabolic stress, and human observation has linked blood levels to age and disease. The registry does hold trial entries, and they are worth reading carefully, because they measure it as a marker rather than give it to anyone. Nobody has ever been administered this.

Preclinical. Cell and animal work reports cytoprotective effects in models of Alzheimer's disease, ischemia, and metabolic stress, and observational human work has associated circulating levels with age and with disease states.

The trial registry does hold entries for it, and they are worth reading carefully, because they measure circulating humanin as a biomarker rather than give it to anyone. There is no interventional study of humanin as a therapy. "Registered trials exist" and "nobody has ever been administered this" are both true at once, and that combination is the whole content of this section.

Safety

In shortNo usable human safety data of any kind. No dose, route or duration in people has been characterized. A mechanism that blocks cell suicide deserves the same caution noted elsewhere here for growth-promoting compounds: stopping programmed cell death is not selectively good, and the cells that should die are the ones most likely to benefit.

No human safety data of any usable kind. There is no dose, route or duration in humans that has been characterized.

An anti-apoptotic mechanism deserves the same caution noted elsewhere in this compendium for pro-growth and pro-angiogenic compounds: suppressing programmed cell death is not selectively good, and cells that should die are the ones most likely to benefit.

Regulatory status

In shortNot approved anywhere, for anything. Research-use-only material with no therapeutic authorization in any country.

Not approved anywhere, for anything. Research-use-only material with no therapeutic authorization in any jurisdiction.

The literature

2 studies indexed. Findings and limitations get equal weight, on purpose.

Always check the primary source

Members area

The Humanin literature needs an account

Everything above is free to read. What an account opens is the evidence underneath it: 2 studies with their limitations, and the regimen each trial actually reported.

  • Every study, with what it found and what it cannot show
  • The limitations, given the same weight as the findings
  • The dose each named trial administered, where recorded
Create a free accountI already have one

Free to create. A membership is separate, and you can decide about that later.

Reading is free, an account is not the same as paying. 80 compound guides, every study with its limitations written underneath, and the regimens those trials actually used. A free account opens all of it. A membership is a separate decision, and it opens the forum. What membership costs.

The wider literature

27 indexed papers and 3 registered trials mentioning Humanin, straight from PubMed and ClinicalTrials.gov. None of those trials administers it; they measure it. These have not been read by us. Unlike the studies above, they carry no findings and no limitations written by anyone here, because writing either would mean claiming a reading nobody has done. They are a starting point for yours.

Registered trials (3)

  1. Comparison of the Effects of General Anesthesia and Combined Spinal-Epidural Anesthesia on Ferroptosis, Humanin and MOTS-c Levels in Renal Transplantation

    University of Gaziantep2026NCT07678073

    interventionalnarecruitingn=68

  2. Clinical Value of Plasma Humanin in Acute Kidney Injury

    Guangdong Provincial People's Hospital2022NCT06105229

    observationalunknownn=60

  3. Humanin Isoforms in Cardiac Muscle and Blood Plasma and Major Complications After Cardiac Operation

    University of Tartu2018NCT03431844

    observationalcompletedn=106

Papers (27)

  1. Aging-associated mitochondrial circular RNAs.

    Mun H, et al.Aging2026PMID 41747288

    journal article

  2. Diagnostic relevance of Humanin, GAS5 and miR-21/miR-103 in prostate disease risk stratification.

    Coradduzza D, et al.Clinical and experimental medicine2025PMID 40768089

    journal article

  3. HUMANIN produced by human efferocytic macrophages promotes the resolution of inflammation.

    Maraux M, et al.Cell death & disease2025PMID 40877234

    journal article

  4. S14G-Humanin ameliorates ovarian dysfunction in a cyclophosphamide-induced premature ovarian insufficiency mouse model.

    Huang J, et al.Molecular human reproduction2025PMID 40811024

    journal articleresearch support, non-u.s. gov't

  5. Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases.

    Thakur R, et al.Molecular neurobiology2025PMID 40715951

    journal articlereview

  6. Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities.

    Li Y, et al.Journal of advanced research2024PMID 38008175

    journal articlereviewresearch support, non-u.s. gov't

  7. Myeloid cells coordinately induce glioma cell-intrinsic and cell-extrinsic pathways for chemoresistance via GP130 signaling.

    Cheng J, et al.Cell reports. Medicine2024PMID 39053460

    journal articleresearch support, non-u.s. gov't

  8. Humanin Treatment Protects Against Venetoclax-Induced Bone Growth Retardation in Ex Vivo Cultured Rat Bones.

    Velentza L, et al.Journal of the Endocrine Society2024PMID 38328478

    journal article

  9. Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.

    Kal S, et al.Peptides2024PMID 38160808

    journal articlereviewresearch support, n.i.h., extramural

  10. Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer's disease.

    Delgado-Peraza F, et al.Alzheimer's research & therapy2023PMID 37730689

    randomized controlled trialjournal articleresearch support, n.i.h., intramuralresearch support, non-u.s. gov't

  11. Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives.

    Karachaliou CE, et al.Biology2023PMID 38132360

    journal articlereview

  12. Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.

    Kim SK, et al.Nature communications2023PMID 37468558

    journal articleresearch support, non-u.s. gov't

  13. Mitochondrial stress and mitokines in aging.

    Burtscher J, et al.Aging cell2023PMID 36642986

    journal articlereviewresearch support, non-u.s. gov't

  14. Editorial: The effects of circulating non-sex hormones in cardiovascular disease.

    Shan SK, et al.Frontiers in endocrinology2022PMID 36605935

    editorialresearch support, non-u.s. gov't

  15. Humanin derivative, HNG, enhances neurotransmitter release.

    Ikegawa N, et al.Biochimica et biophysica acta. General subjects2022PMID 35843407

    journal articleresearch support, non-u.s. gov't

  16. An evidence of Humanin-like peptide and Humanin mediated cryosurvival of spermatozoa in buffalo bulls.

    Katiyar R, et al.Theriogenology2022PMID 36183493

    journal article

  17. Mitochondria-derived peptides in aging and healthspan.

    Miller B, et al.The Journal of clinical investigation2022PMID 35499074

    journal articlereviewresearch support, n.i.h., extramural

  18. Mitochondrial-derived peptides and exercise.

    Woodhead JST, et al.Biochimica et biophysica acta. General subjects2021PMID 34520826

    journal articlereview

  19. Detection of mitochondria-pertinent components in exosomes.

    Wang X, et al.Mitochondrion2020PMID 32980480

    journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov't

  20. Humanin: A mitochondria-derived peptide with emerging properties.

    Rochette LAnnales de cardiologie et d'angeiologie2020PMID 32800320

    editorial

  21. Neurobiological roots of psychopathy.

    Tiihonen J, et al.Molecular psychiatry2020PMID 31455857

    journal articleresearch support, non-u.s. gov't

  22. Mitochondrial-derived peptides in energy metabolism.

    Merry TL, et al.American journal of physiology. Endocrinology and metabolism2020PMID 32776825

    journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov'treview

  23. Mitochondrial peptides-appropriate options for therapeutic exploitation.

    Popov LDCell and tissue research2019PMID 31131430

    journal articlereview

  24. Effects of prolonged type 2 diabetes on mitochondrial function in cerebral blood vessels.

    Merdzo I, et al.American journal of physiology. Heart and circulatory physiology2019PMID 31490734

    journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov't

  25. Mitochondrial-Derived Peptides Exacerbate Senescence.

    Mendelsohn AR, et al.Rejuvenation research2018PMID 30058454

    journal articlereview

  26. Humanin inhibits apoptosis in pituitary tumor cells through several signaling pathways including NF-κB activation.

    Gottardo MF, et al.Journal of cell communication and signaling2017PMID 28378125

    journal article

  27. A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity.

    Caricasole A, et al.FASEB journal : official publication of the Federation of American Societies for Experimental Biology2002PMID 12154011

    journal article

Discussion

Humanin has its own forum, and sits in Longevity & Healthspan. Every post says what kind of claim it makes.

All threads
Personal anecdote0Cited research0Question0Discussion1

Membership

Peptides are free. The argument is for members.

The guide above is open to everyone, and the literature underneath it opens with a free account. That is the educational half of this site. Reading and joining the discussion around Humanin, and every other entry, is what membership pays for.

Unlock membershipSign in

From $3.33 a month, billed annually. Cancel anytime.

For Research & Educational Discussion Only. Not Medical Advice

This guide is educational reference material compiled from published literature. It is not medical advice, not a recommendation, and not a substitute for a clinician who knows your history. Nothing here should be used to make a decision about your own health without one.

Talk to a licensed healthcare professional.