Humanin
Research Guide

Research Overview

Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 16S rRNA (MT-RNR2) region. It was originally identified as a factor that rescued neuronal cells from death in Alzheimer's-disease cell models, and it has since been studied broadly as a cytoprotective, anti-apoptotic bioregulator in a range of in-vitro and preclinical systems (PMID 35372353, 38132360).

In the research literature, humanin is characterized as a stress-responsive peptide that helps preserve mitochondrial function under cellular stress and senescence. It has been described acting through both an intracellular arm (binding pro-apoptotic Bcl-2-family proteins) and a secreted, extracellular arm (signaling through cell-surface receptor complexes). Reported downstream associations include reduced oxidative stress and lower pro-inflammatory cytokine expression in model systems (PMID 33130077, 42193373).

This page is a laboratory reference for researchers sourcing the wild-type 24-mer peptide. Note that the widely sold analog HNG / S14G-Humanin is a different molecule with a different sequence and CAS number. Confirm which molecule a given lot actually is against the batch COA and label. All statements here describe reported in-vitro and preclinical research context only; no human efficacy is established or implied.

Mechanism Summary

Mechanisms reported in the in-vitro and preclinical research literature include:

• Humanin has been characterized in vitro and in preclinical models as a cytoprotective, anti-apoptotic peptide that helps preserve mitochondrial function under cellular stress and senescence (reviewed PMID 35372353, 37106758, 33130077). Reported mechanisms are commonly described in two arms, intracellular and extracellular.
• Intracellular arm: humanin has been reported to bind the pro-apoptotic Bcl-2-family proteins Bax, Bim and tBid, and to bind IGFBP3, associations that in cell models are linked to inhibition of caspase activation and of mitochondrial-pathway apoptosis (PMID 35372353, 33130077).
• Extracellular / secreted arm: as a secreted peptide, humanin has been reported to signal through the G-protein-coupled formyl peptide receptor-like 1/2 (FPRL1/FPR2) to modulate ASK1 and JNK signaling, and through a trimeric CNTFR-alpha / gp130 / WSX-1 receptor complex associated with activation of JAK2/STAT3 cascades. It also interacts with the soluble partners VSTM2L and IGFBP3 (PMID 35372353).
• Downstream, preclinical studies associate humanin and its analogs with reduced oxidative stress, suppression of mitochondrial fission proteins (Drp1, Fis1), improved mitochondrial ultrastructure, and lower pro-inflammatory cytokine expression such as IL-1beta and IL-6 (PMID 42193373).
• Structure-activity work indicates the peptide is largely disordered in aqueous buffer and converts to an anti-parallel beta-sheet on negatively charged membranes. Ser7 and Cys8 are reported to be important for activity (S7A and C8A analogs are described as inactive), while the S14G substitution (the HNG analog) is reported to be roughly 1000-fold more potent than wild-type in neuroprotection assays (PMID 21215775, 24247787).
• All mechanism statements above are reported in-vitro and preclinical associations only. No human efficacy is established or implied.

Reference Data

Identity values are compiled from public chemistry databases and vendor documentation. Confirm the exact salt form, molecular weight, and purity for a given batch against its Certificate of Analysis (COA).

Research Applications

In laboratory research, Humanin is studied in contexts such as:

• Neuroprotection / Alzheimer's-disease models: originally identified as a factor that rescued neuronal cells from AD-associated insults; studied in vitro and in vivo for neuroprotective activity (PMID 38132360, 35372353)
• Cellular aging and senescence: investigated as a preserver of mitochondrial function and cell viability under senescence and stress conditions (systematic review PMID 37106758)
• Cardiovascular / atrial fibrillation: humanin and the HNG analog studied in an AngII-induced mouse model where they were associated with reduced atrial fibrosis, improved mitochondrial ultrastructure, and lower AF inducibility (PMID 42193373); circulating humanin isoforms studied as observational biomarkers around cardiac surgery (NCT03431844)
• Age-related macular degeneration (AMD) / retinal (RPE) protection: reviewed as a cytoprotective MDP for mitochondrial and cellular health in AMD models (PMID 32365540)
• Diabetes / insulin sensitivity: investigated in vitro and in vivo for reported effects on insulin sensitivity, pancreatic beta-cell survival, and glucose-stimulated insulin secretion (review PMID 35432758; preclinical PMID 39823439)
• Apoptosis-related model systems broadly: studied as an anti-apoptotic peptide across leukocytes, germ cells, neurons and other tissues via JAK/STAT and Bcl-2-family interactions (PMID 33130077)
• Cancer biology (context-dependent): reviewed as a research target with a debated, dual role in tumor progression and chemoresistance; also reported to enhance the pro-apoptotic activity of TNF-alpha in some cancer contexts (PMID 30582721, 33130077)
• Skeletal / tissue regeneration: emerging preclinical interest in reported regulation of osteoclasts, osteoblasts and chondrocytes (PMID 35372353)
• Renal research (acute kidney injury / transplantation): plasma humanin studied observationally as a candidate marker (NCT06105229; NCT07678073, alongside MOTS-c and ferroptosis markers)

Storage Information

• Lyophilized powder: keep the freeze-dried peptide sealed, protected from light and moisture, and stored frozen (research vendors commonly cite -20 C or colder). The lyophilized form is generally the most stable for long-term storage. See the Lyophilized Storage Guide for general practice.
• Reconstitution: dissolve in bacteriostatic water (0.9% benzyl alcohol) or sterile water, adding solvent slowly down the vial wall and swirling gently. Do not shake or vortex, since foaming and mechanical shear can degrade the peptide. Use the Reconstitution Calculator to work out concentration (for example, a 5 mg vial plus 1 mL diluent gives 5 mg/mL, which is arithmetic only and not a use directive).
• Reconstituted solution: refrigerate at 2 to 8 C; vendor guidance commonly cites use within roughly 28 to 60 days for potency, though the exact validated shelf life for a specific product should be confirmed against supplier data. Avoid repeated freeze-thaw of the solution, since ice-crystal formation can damage peptide structure.
• Structure and stability notes: humanin is largely disordered in aqueous buffer and forms an anti-parallel beta-sheet on negatively charged membranes; the single cysteine (Cys8) means free-thiol oxidation and disulfide-mediated aggregation are plausible degradation routes to control for (PMID 21215775, 24247787). Confirm handling of the thiol, aggregation limits, and HPLC purity against the batch COA.