Humanin

Research Reagent · Laboratory Use Only

What is humanin and what does current research show about its biological functions?

Humanin is a 21-amino acid mitochondria-derived peptide first identified in 2001 from the surviving neurons of Alzheimer's disease patients. Preclinical research published in PNAS and Nature Medicine suggests it exerts cytoprotective, anti-apoptotic, and metabolic-regulatory effects, with studies indicating potential roles in neuroprotection, insulin sensitivity, and longevity pathways via STAT3 and IGF-1 signalling.

Scientific AbstractPMID 41975304 · 2026

Background

Brain aging leads to structural changes, especially atrophy, which can result in dysfunction. Mitochondrial dysfunction is thought to explain the structural changes in brain aging.

Objective

This study aimed to investigate the effects of a 12-week water-based resistance training (WBRT) program on brain structural integrity, mitochondrial-related growth factors, oxidative stress, and inflammation in older women.

Methods

A total of 24 older women (mean age:66) were randomly assigned to a WBRT group (n = 12) or a control (CON) group (n = 12). Participants in the WBRT group performed supervised resistance training in water three times per week for 12 weeks. Brain structural changes were assessed using magnetic resonance imaging (MRI), and blood samples were analyzed for Humanin (HN), Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF-15), Brain-Derived Neurotrophic Factor (BDNF), and Insulin-like Growth Factor 1 (IGF-1) as well as oxidative and inflammation biomarkers.

Results

The WBRT group showed significant increases in gray matter, subcortical gray matter, cerebellar gray matter volume, and cerebrum white matter compared to the CON group (p < 0.05). Furthermore, WBRT resulted in significant increases in BDNF, IGF-1, FGF21, and GDF-15 levels (p < 0.05). Malondialdehyde decreased, and glutathione peroxidase increased, with significant reductions in tumor necrosis factor-alpha and an increase in interleukin-10 in the WBRT group compared to the CON group (p < 0.05), suggesting anti-inflammatory and antioxidant effects of WBRT.

Conclusion

These findings support the potential beneficial effects of WBRT as a non-pharmacological intervention to counteract age-related brain atrophy and promote brain health in aging populations.

Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Humanin?

Humanin is a 24-amino acid peptide encoded by a mitochondrial open reading frame (mORF) that functions as a neuroprotective and cytoprotective agent in cellular stress models. It exhibits anti-apoptotic properties and modulates multiple signaling cascades involved in cell survival and metabolic homeostasis.

Mechanism of Action

Humanin operates through binding to a heteromeric receptor complex composed of FPRL1 (formyl peptide receptor-like 1) and IL-6Rα, initiating downstream JAK-STAT3 and PI3K/Akt pathway activation. This signaling cascade suppresses pro-apoptotic factors (including BAD and caspase-3) while upregulating anti-apoptotic proteins like Bcl-2. The peptide also exhibits direct mitochondrial effects, stabilizing cytochrome c retention and reducing reactive oxygen species (ROS) production under oxidative stress conditions.

Observed Laboratory Results

  • Demonstrates neuroprotection against Alzheimer's disease-related amyloid-beta (Aβ) toxicity in primary neuronal cultures with IC₅₀ values in the picomolar range
  • Reduces cell death by 40-60% in serum deprivation and oxidative stress models across multiple cell types
  • Activates STAT3 phosphorylation within 5-15 minutes of treatment, indicating rapid receptor-mediated signaling engagement
Clinical Research Parameters
6 trials4 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

ClinicalTrials.gov ↗
NCT06125249
UNKNOWNN/An=60

Humanin's Value for Early Diagnosis and Short-term Prognosis in Patients With AKI After Heart Transplantation

The goal of this observational study is to explore the value of Humanin for early diagnosis and short-term prognosis of AKI patients after heart transplantation. The main question it aims to answer are:whether Humanin can be a novel marker for predicting AKI after heart transplantation Researchers will compare the Humanin concentration in patients with AKI did not occur after heart transplantation

Primary Endpoints
Humanin concentration; Serum creatinine concentration
Study Period
2022-07-01 → 2024-06
NCT06105229
UNKNOWNN/An=60

Clinical Value of Plasma Humanin in Acute Kidney Injury

The goal of this observational study is to assess the clinical value of humanin in acute kidney injury. The main questions it aims to answer are:whether Humanin can be a novel marker for predicting AKI Researchers will compare humanin concentration in healthy people to see if humanin can be a novel marker for predicting AKI

Primary Endpoints
Humanin concentration; Serum creatinine concentration
Study Period
2022-08-01 → 2024-06
NCT03431844
COMPLETEDN/An=106

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

Objective of the study is to clarify humanin-like peptide concentration in myocard tissue and in blood and to study if its concentration level is related to early complication occurrence and frequency after cardiac operation. Hypothesis of the study is that previously described elements are related to each other.

Primary Endpoints
Mortality; Major complications: myocardial infarction.
Study Period
2018-01-01 → 2019-08-31
NCT05506228
RECRUITINGN/An=150

How Are the Muscles Affected in Cerebral Palsy? A Study of Muscle Biopsies Taken During Orthopaedic Surgery.

* Cerebral palsy (CP) is a motor disorder caused by an injury to the immature brain. Even though the brain damage does not change, children with CP will have progressively weaker, shorter and stiffer muscles that will lead to contractures, bony deformations, difficulty to walk and impaired manual ability. An acquired brain injury (ABI) later during childhood, such as after a stroke or an injury, w

Study Interventions
No intervention
Primary Endpoints
Muscle/tendon morphology; Muscle metabolism
Study Period
2002-01-15 → 2033-12-15
NCT04104958
UNKNOWNN/An=100

IVF Outcome in Polycystic Ovary Syndrome Patients

1. To investigate the circulating concentrations of phoenixin and their associations with BMI, the concentrations of sex hormones including (LH), (FSH), (E2), (P4), (TT) and steroid hormones enzyme in PCOS patients. 2. To detect the expression PNX and humanin in women with or without PCOS and to elucidate possible correlations with ovarian reserve and clinical outcomes after IVF-ICSI. 3. To invest

Study Interventions
qRTPCR (mRNA level).
Primary Endpoints
Detect difference in expression of phoenixin and humanin in PCOS; Assess the link between phoenixin and humanin through the PI3/AKT/mTOR
Study Period
2020-03-01 → 2021-02-15
NCT07438002
RECRUITINGN/An=50

Analysis of Effects of High-intensity Physical Exercise in Subjects With Dialyzed Chronic Kidney Disease and in Conservative Treatment

This study aims to analyze the effects of physical activity in patients with chronic kidney disease undergoing dialysis or conservative treatment. Patients will be randomized into two groups: combined exercise (high-intensity aerobic resistance + strength training) and control group

Study Interventions
Exercise, control
Primary Endpoints
Gait speed (6MWT); Physical performance (SPPB)
Study Period
2025-09-02 → 2026-09

All data presented on this page is for laboratory research purposes only. Humanin is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 41975304) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.