Humanin
Mitochondrial-derived peptide
A 24-amino-acid mitochondrial-derived peptide studied in cytoprotection and cellular-aging research.
Also referenced as: HN, MT-RNR2 peptide
Overview
Humanin is a small mitochondrial-derived peptide encoded within the mitochondrial 16S ribosomal RNA gene (MT-RNR2). It was identified in the early 2000s from surviving neurons in Alzheimer's disease brain tissue and is one of the first characterized mitochondrial-derived peptides.
At a glance
What Humanin does
Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded within the 16S rRNA region of mitochondrial DNA, and it functions as a cytoprotective, stress-resistance signal that helps cells survive metabolic and apoptotic insults. It was originally discovered for its ability to protect neurons from amyloid-beta toxicity, and its broad theme is anti-apoptotic protection: it acts both intracellularly, by directly binding pro-apoptotic BCL-2-family proteins, and extracellularly, as a secreted factor that signals through cell-surface receptors.
Mechanistically, inside the cell humanin binds BAX and prevents its translocation to the mitochondrial outer membrane, blocking the pore formation that initiates apoptosis; it also binds tBID and BimEL (BCL2L11) and interacts with IGFBP3, where it can block IGFBP3-induced apoptosis in glial cells. As a secreted ligand it engages a trimeric receptor and a GP130/IL6ST-containing complex to activate the AKT, ERK1/2, and STAT3 signaling pathways (via PI3K, MEK, and JAK respectively), promoting cell survival and modulating stress responses in an age-dependent manner in tissues such as the hippocampus.
Biologically, humanin levels tend to decline with age, and it has been studied for cytoprotective and metabolic effects, including improved insulin sensitivity and neuroprotection, in cell and animal models. Human data are largely associative: circulating humanin correlates with aging and certain disease states. It remains a preclinical/experimental molecule for longevity purposes, with well-mapped molecular mechanisms but no established human therapeutic use, so its anti-aging promise rests on mechanistic and animal evidence rather than clinical proof.
Effects reported in research
- Binds pro-apoptotic BAX and prevents its translocation to the mitochondrial outer membrane, blocking apoptosis initiation (mechanistic/in-vitro).
- Also binds tBID and BimEL (BCL2L11), extending its anti-apoptotic reach across multiple BCL-2-family triggers.
- Interacts with IGFBP3 and can block IGFBP3-induced apoptosis in glial cell lines (in-vitro).
- As a secreted factor, signals through a GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 survival pathways (via PI3K, MEK, JAK).
- Protects neurons from amyloid-beta-induced toxicity, its original discovery context (in-vitro/preclinical).
- Improved insulin sensitivity and exerted metabolic/cytoprotective effects in cell and animal models (preclinical).
- Shows age-dependent signaling differences (e.g., in the hippocampus), and circulating levels tend to decline with aging in humans (associative).
- Remains a preclinical/experimental molecule with well-characterized mechanisms but no established human therapeutic use for longevity.
Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.
Mechanism of action
Humanin is reported to have cytoprotective and anti-apoptotic effects. Described mechanisms include interaction with pro-apoptotic Bcl-2 family proteins (such as Bax and BID) and signaling through a cell-surface receptor complex, with downstream effects on cell survival pathways. It has also been studied for roles in metabolic regulation and insulin sensitivity. Both a 24-amino-acid form (mitochondrial translation) and a 21-amino-acid form (cytoplasmic translation) have been described.
Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
What it's studied for
Research contexts in which Humanin appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.
Key characteristics
- One of the first identified mitochondrial-derived peptides (from MT-RNR2)
- Discovered from surviving neurons in Alzheimer's disease brain tissue
- Reported cytoprotective and anti-apoptotic activity
- Exists in 24-aa (mitochondrial) and 21-aa (cytoplasmic) forms
- Studied for neuroprotection, metabolism, and aging biology
- Evidence is largely preclinical; no established human therapies
Reported research dosing reference only
Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. Humanin is a research compound.
Humanin dosing is essentially preclinical, drawn from cell and animal studies using native humanin or the more potent HNG analog; no established human research dose exists. These are reference figures for research context only, not dosing guidance for humans.
- Rodent studies: microgram-to-milligram/kg intraperitoneal or intracerebroventricular doses of humanin or HNG analog
- No standardized human research dose is established
Native humanin has limited stability and short half-life, which is why many studies use the more stable, higher-potency HNG (S14G) analog. Human pharmacokinetics are not well defined.
How it compares
Humanin is a naturally encoded mitochondrial-derived signaling peptide focused on cytoprotection and metabolism, distinct from the synthetic mitochondria-targeting SS-31 and from immune or pineal peptides.
Commonly studied alongside
Compounds frequently researched together with Humanin in the literature. Cross-referenced for research context — not a usage or combination recommendation.
Compare and calculate
Side-by-side pages for the pairings the literature already documents for Humanin, plus the unit-conversion reference for a reconstituted vial. Factual comparisons of documented characteristics — not a recommendation to combine or use any compound.
Handling & Stability
Lyophilized peptides are stored cold, protected from light, and reconstituted only at the time of intended in-vitro work.
- Avoid repeated freeze-thaw cycles
- Verify supplier lot and Certificate of Analysis
- Follow institutional lab-safety protocols
Analytical & COA Concepts
Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:
Category Context
Humanin sits in the Longevity & Cellular area of the PeptiDex library.
- Entry type: Research compound reference
- Longevity & Cellular category hub →
- Browse the full library →
- Glossary of terms →
Where researchers source Humanin
For researchers studying Humanin, third-party suppliers such as Practically Natty Peptides offer research-grade material, third-party tests every batch and provides Certificates of Analysis on request, and ship from the US.
PeptiDex does not maintain a direct supplier listing for this compound. The link above goes to a third-party research-supplier directory.
Frequently asked questions
What is humanin?
Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded within the 16S rRNA region of mitochondrial DNA, discovered in 2001. It is the founding member of the mitochondrial-derived peptide family and is studied for cytoprotective, neuroprotective, and metabolic effects.
What is the sequence and molecular weight of humanin?
Humanin's sequence is MAPRGFSCLLLLTSEIDLPVKRRA, a 24-residue peptide with an approximate molecular weight of about 2687 Da. Some research analogs (e.g. HNG, with a Ser14Gly substitution) are more potent variants used in studies.
What is humanin studied for?
Preclinical research has examined humanin for neuroprotection against amyloid-beta toxicity, cardioprotection in ischemia-reperfusion injury, insulin sensitization via central STAT3 signaling, and anti-apoptotic effects through BAX antagonism. These are cell and animal findings, not established human therapies.
How does humanin protect cells?
Humanin acts through several mechanisms: binding a trimeric receptor complex (CNTFR/WSX-1/gp130) to activate JAK2/STAT3 signaling, directly antagonizing the pro-apoptotic protein BAX, and modulating IGF-1 signaling via IGFBP-3. Together these are thought to underlie its reported cytoprotective and stress-resistance effects.
How does humanin relate to aging?
Circulating humanin levels decline with age in humans and other species, and higher levels have been associated with longevity in some cohorts. This makes it a candidate biomarker and target in aging and mitochondrial-stress research, though causal effects in humans remain under investigation.
Answers are educational summaries of research-literature context and do not constitute medical advice. See the Research Library, COA guide, and Storage & Handling guide for more.
References
Primary literature indexed in PubMed for Humanin. Listing a study records that it exists and is indexed — it is not a claim of efficacy, a therapeutic indication, or an endorsement of its conclusions. Much of this literature is preclinical (in-vitro or animal-model).
- The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan
- Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives
Each reference was checked against its PubMed record on 2026-07-28: the PMID resolves and the title, journal and year match. Where no indexed literature exists for a compound, PeptiDex says so rather than substituting a citation about a different molecule. See the editorial policy.