Humanin

Key Benefits#

• Neuroprotection against amyloid-beta toxicity (Alzheimer's relevance)
• Inhibits cellular apoptosis
• Improves insulin sensitivity
• Reduces cardiovascular risk markers
• Anti-inflammatory effects
• Correlates with longevity in centenarian studies
• Protects against ischemic injury
• Potential cancer cell apoptosis sensitization

Mechanism of Action#

Humanin is a 21-amino acid peptide that acts as an endogenous cytoprotective factor. It activates STAT3 and MAPK pathways to inhibit apoptosis triggered by amyloid-beta, ischemia, and oxidative stress. It also binds to the trimeric humanin receptor complex (CNTFR/WSX-1/gp130) on cell surfaces to regulate insulin sensitivity and systemic metabolism. Blood levels correlate inversely with age and with metabolic syndrome. HNG (Gly substitution at position 14) has dramatically enhanced receptor affinity.

Dosing Protocols#

Side Effects#

• Injection site irritation
• Limited human safety data available

Contraindications#

Pregnancy or breastfeeding. Insufficient human safety data for definitive contraindication list.

Storage#

Lyophilized powder: store at −20°C. Reconstituted: refrigerate at 2–8°C, use within 14 days.

Featured In Stacks#

1. 1.
   The Complete Mitogenome of Haemaphysalis parva (Arachnida: Ixodidae) and Comparative Mitogenomics of Haemaphysalis Species

   Aydemir HB, Keskin A · Acta parasitologica · 2026PubMed Verified

2. 2.
   Mitochondrial-derived peptides MOTS-c and humanin attenuate dexamethasone-induced atrophy in human skeletal muscle cells

   Elhusseiny R, Ihsan M, Bellefroid T, Farooq A, Racinais S, Deldicque L · Physiological reports · 2026PubMed Verified

3. 3.
   Mitochondrial derived peptide humanin improved semen quality, semen freezability, antioxidant status and in-vitro fertility in crossbred bull

   Gemeda AE, Singh M, Katiyar R, Kumar A, Pande M, Patra MK et al. · Scientific reports · 2026PubMed Verified

4. 4.
   Mitochondrial-derived microproteins in lung disease: insights and implications

   Behan M, Yen K, Cohen P, Kliment CR · American journal of physiology. Lung cellular and molecular physiology · 2026ReviewPubMed Verified

5. 5.
   Humanin improves bone health in a glucocorticoid-treated mouse model of Duchenne muscular dystrophy

   Cedervall T, Jude B, von Walden F, Velentza L, Lanner JT, Sejersen T et al. · Biochemistry and biophysics reports · 2026PubMed Verified

6. 6.
   Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets

   Thoudam T, Zeng G, Gao H, Jiang Y, Huda N, Yang Z et al. · Hepatology communications · 2026ReviewPubMed Verified

7. 7.
   Diagnostic potential of serum humanin in breast cancer among the Egyptian population

   Mohamed MH, Kamel WT, Ibrahim EH, Makboul A, Elemary AN, Mohammed DA · Discover oncology · 2026PubMed Verified

8. 8.
   Interlaced roles of mitochondrial DNA in colorectal cancer: Liquid-biopsy biomarkers, nuclear mtDNA-driven genomic instability, and mito-encoded micro peptide signaling

   Koo TH, Leong XB, Lee YL, Hayati F, Zakaria AD · World journal of gastrointestinal oncology · 2025ReviewPubMed Verified

9. 9.
   Mitochondrial-derived microproteins in cancer and neurodegeneration: A new era of cross-disease mechanistic insights

   Hu S, Hu C, Tong M · Pathology, research and practice · 2026ReviewPubMed Verified

10. 10.
    Enduring Effects of Humanin on Mitochondrial Systems in TBI Pathology

    Thapak P, Ying Z, Gomez-Pinilla F · Biomolecules · 2025PubMed Verified

11. 11.
    SHLP2 restores pre-osteoblastic cells against oxidative stress-induced inflammaging

    Ryu JH, Mangal U, Kim JH, Yang DJ, Lee KJ, Choi YH et al. · Scientific reports · 2025PubMed Verified

12. 12.
    Insights into the Biomarker Potential of Humanin and Mots-c Expression and Telomere Length in Alzheimer's Disease

    Rodríguez-Esparragón F, Cazorla-Rivero SE, Torrealba E, Cánovas-Molina Á, González-Hernández AN, Martín-Alfaro R et al. · International journal of molecular sciences · 2025PubMed Verified

13. 13.
    Research Progress on Signalling Pathways Related to Sepsis-Associated Acute Kidney Injury in Children

    Zhang Z, Sheng M, Bao Y, Tang C · Current issues in molecular biology · 2025ReviewPubMed Verified

14. 14.
    Serum mtDNA DAMP abundance, fragmentation and heteroplasmic variants associate with Acute Respiratory Failure outcome: A secondary analysis of study NCT00976833

    Daly GT, Hartsell EM, Pastukh VM, Roberts JT, Haastrup AI, Purcell LD et al. · medRxiv : the preprint server for health sciences · 2025PubMed Verified

15. 15.
    Redox-sensitive miRNAs and Humanin could mediate effects of exercise and astaxanthin on oxidative stress and inflammation in type 2 diabetes

    Basereh A, Khoramipour K, Hosseini N, HajHosseini M, Khodabakhshi A, Amirkhosravi L et al. · Scientific reports · 2025RCTPubMed Verified

16. 16.
    Herkinorin Promotes μ-Opioid Receptor Internalization and Protects iPSC-Derived Neurons from Hypoxic/Ischemic Injury

    Ju Z, Wang G, Yan Y, Liang X, Cui X · Journal of integrative neuroscience · 2025PubMed Verified

17. 17.
    Assessment of mitochondrial peptide humanin in women with polycystic ovary syndrome: serum and skeletal muscle profile

    Kutuk IS, Akin S, Demirel H, Mumusoglu S, Ciftci T, Yildiz BO · Journal of endocrinological investigation · 2025PubMed Verified

18. 18.
    Nitrosative Stress, Mitochondrial Peptides, and Ferroptosis Markers in Corneal Epithelial Cells from Keratoconus Patients

    Demirkiran C, Mete A, Demiryürek AT, Saracaloglu A, Demiryürek Ş · Current eye research · 2026PubMed Verified

19. 19.
    Hierarchical random forest model, inflammation and oxidative stress as predictors of the atherogenic index of plasma and diabetes progression

    Jelinek HF, Muteir I, Al-Aubaidy H · Scientific reports · 2025PubMed Verified

20. 20.
    Exercise Improves Cardiac Dysfunction in D-Galactose-Treated Rats by Regulation of IGF-1-Humanin Pathway

    Askarimoghadam H, Rostamzadeh F, Mirtajaddini Goki M, Jafari E, Yeganeh-Hajahmadi M · Journal of aging research · 2025PubMed Verified

21. 21.
    In-silico modeling of SHLP6: A novel mitochondrial peptide controlling neurodegeneration and cellular aging

    Kannan HT, Umapathy S, Pan I · Computers in biology and medicine · 2025PubMed Verified

22. 22.
    HUMANIN produced by human efferocytic macrophages promotes the resolution of inflammation

    Maraux M, Vetter M, Zuffo LD, Bonnefoy F, Wetzel A, Varin A et al. · Cell death & disease · 2025PubMed Verified

23. 23.
    Detection of Mitochondrial-Derived Peptide Humanin in Semen and Reproductive Tract of Caprine Along With Its Relation to Seasonality

    Chouksey S, Shukla SN, Dubey A, Soni Y, Mandal S, Chourasia A · Reproduction in domestic animals = Zuchthygiene · 2025PubMed Verified

24. 24.
    S14G-Humanin ameliorates ovarian dysfunction in a cyclophosphamide-induced premature ovarian insufficiency mouse model

    Huang J, Zhang D, Zou L, Liu H, Xia W, Zhu C et al. · Molecular human reproduction · 2025PubMed Verified

25. 25.
    Diagnostic relevance of Humanin, GAS5 and miR-21/miR-103 in prostate disease risk stratification

    Coradduzza D, Cruciani S, Sibono L, Tedde A, Zinellu A, Maioli M et al. · Clinical and experimental medicine · 2025PubMed Verified

26. 26.
    Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases

    Thakur R, Chauhan A, Moudgil H, Singh S, Devi R · Molecular neurobiology · 2025ReviewPubMed Verified

27. 27.
    The unexplored Nexus: Mitochondria derived microproteins and Parkinson's disease

    Patel K, Soni R, Shah J · Pathology, research and practice · 2025ReviewPubMed Verified

28. 28.
    Ameliorative effects of Gly[14]-humanin on cyclophosphamide-induced premature ovarian insufficiency and underlying mechanisms

    Huang J, Liu Y, Zou L, Zhu C, Xia W · Reproductive biomedicine online · 2025PubMed Verified

29. 29.
    Mitochondrial-Derived Peptides as Therapeutics and Biomarkers for Combating Vascular Aging and Associated Cardiovascular Diseases

    Sivakumar R, Senghor KAA, Vinodhini VM, Kumar J · Current cardiology reviews · 2025PubMed Verified

30. 30.
    Humanin variants aggregate to produce different fibril morphologies

    Morris DL, Nyenhuis SB, Gruschus JM, Nyenhuis DA, Puja R, Hinshaw JE et al. · The Journal of biological chemistry · 2025PubMed Verified

31. 31.
    SHLP6: a novel NLRP3 and Cav1 modulating agent in Cu-induced oxidative stress and neurodegeneration

    Thamarai Kannan H, Umapathy S, Pan I · Frontiers in molecular neuroscience · 2025PubMed Verified

32. 32.
    The neuroprotective role of Humanin in Alzheimer's disease: The molecular effects

    Alqahtani SM, Al-Kuraishy HM, Al-Gareeb AI, Alexiou A, Fawzy MN, Papadakis M et al. · European journal of pharmacology · 2025ReviewPubMed Verified

33. 33.
    Mitochondria‑derived peptides: Promising microproteins in cardiovascular diseases (Review)

    Ran Y, Guo Z, Zhang L, Li H, Zhang X, Guan X et al. · Molecular medicine reports · 2025ReviewPubMed Verified

34. 34.
    Exploring the therapeutic potential of MOTS-c in age-related macular degeneration: from cellular responses to patient-derived cybrids

    Mohtashami Z, Schneider K, Azimi R, Atilano S, Chwa M, Kenney MC et al. · Human cell · 2025PubMed Verified

35. 35.
    A Review on the Potential Role of Humanin Peptide and its Analogs in the Regulation of Autophagy Pathways for Therapeutic Application in Metabolic Disorders

    Moin H, Ashraf R, Butt B, Mustafa I, Shafiq M, Shah SAR · Protein and peptide letters · 2025ReviewPubMed Verified

36. 36.
    Potential Role of High-Intensity Interval Training-Induced Increase in Humanin Levels for the Management of Type 2 Diabetes

    Soltany A, Daryanoosh F, Gholampour F, Sadat Hosseini N, Khoramipour K · Journal of cellular and molecular medicine · 2025PubMed Verified

37. 37.
    Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study

    Zhu D, Wang Z, Li Y, Chen S, Kang X · Journal of orthopaedic translation · 2025PubMed Verified

38. 38.
    Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study

    Coradduzza D, Cruciani S, Di Lorenzo B, De Miglio MR, Zinellu A, Maioli M et al. · Non-coding RNA · 2025PubMed Verified

39. 39.
    Hepatic and Pancreatic Cellular Response to Early Life Nutritional Mismatch

    Ghosh S, Ganguly A, Habib M, Shin BC, Thamotharan S, Andersson S et al. · Endocrinology · 2025PubMed Verified

40. 40.
    Humanin alone and in combination with GnRHa therapy attenuates ovarian dysfunction induced by prepubertal cyclophosphamide chemotherapy in female mice

    Liu L, Wang H, Wen W, Wang S, Zuo L, Cheng Y et al. · Reproductive toxicology (Elmsford, N.Y.) · 2025PubMed Verified

41. 41.
    [Gly14]-Humanin ameliorates high glucose-induced endothelial senescence via SIRT6

    Li M, Liu Z, Cao X, Xiao W, Wang S, Zhao C et al. · Scientific reports · 2024PubMed Verified

42. 42.
    Evaluation of vascular peroxidase 1, humanin, MOTS-c and miR-200c expression levels in untreated preeclampsia patients

    Coskun E, Ekmekci OB, Gungor Z, Tuten A, Oncul M, Hamzaoğlu K et al. · Molecular biology reports · 2024PubMed Verified

43. 43.
    Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening

    Lim YW, Quinn R, Bharti K, Ferrer M, Zarkoob H, Song MJ · Biofabrication · 2024PubMed Verified

44. 44.
    Comparison of the Mitophagy and Apoptosis Related Gene Expressions in Waste Embryo Culture Medium of Female Infertility Types

    Kütük D, Öner Ç, Başar M, Akcay B, Olcay İO, Çolak E et al. · Life (Basel, Switzerland) · 2024PubMed Verified

45. 45.
    Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms

    Amman AM, Wolfe V, Piraino G, Ziady A, Zingarelli B · Biomedicines · 2024PubMed Verified

46. 46.
    The impact of prebiotics and probiotics on the oral microbiome of individuals with periodontal disease: a scoping review

    Doucette H, Ward R, Wheeldon C, Whelan A · Canadian journal of dental hygiene : CJDH = Journal canadien de l'hygiene dentaire : JCHD · 2024PubMed Verified

47. 47.
    Humanin attenuates metabolic, toxic, and traumatic neuropathic pain in mice by protecting against oxidative stress and increasing inflammatory cytokine

    Bilgin B, Hekim MG, Bulut F, Kelestemur MM, Adam M, Ozcan S et al. · Neuropharmacology · 2025PubMed Verified

48. 48.
    Oligoasthenozoospermia is alleviated in a mouse model by [Gly14]-humanin-mediated attenuation of oxidative stress and ferroptosis

    Liu Y, Feng Q, Zou L, Zhu C, Xia W · Andrology · 2025PubMed Verified

49. 49.
    Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin

    Lu Y, Bartoszek EM, Cortada M, Bodmer D, Levano Huaman S · Cell death discovery · 2024PubMed Verified

50. 50.
    Quantitative proteomics analysis reveals the protective role of S14G-humanin in septic acute kidney injury using 4D-label-free and PRM Approaches

    Shi Q, Xiao Z, Cai W, Chen Y, Liang H, Ye Z et al. · Biochemical and biophysical research communications · 2024PubMed Verified