--- title: "Humanin | PepTracker Pro" url: https://peptrackerpro.com/peptides/humanin description: "An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians." lang: en --- Skip to main content **Educational information only.** This site does not provide medical advice. Read full disclaimer (https://peptrackerpro.com/disclaimer) **Research-only content.** This page is for educational purposes and does not constitute medical advice. Read full disclaimer → (https://peptrackerpro.com/research-disclaimer) # Humanin Low Evidence An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians. Aliases HN +3 more Evidence Low Evidence Last Updated 2026-06-21 Reading Time 4 min ## What It Is Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA region (MT-RNR2) of mitochondrial DNA. It was first identified in 2001 by Hashimoto and colleagues from the surviving occipital-lobe tissue of a patient with Alzheimer's disease, where it was found to protect neurons from amyloid-beta and familial-Alzheimer's gene toxicity. Alongside MOTS-c, humanin is one of the most studied members of the emerging mitochondrial-derived peptide family, and it has gained renewed research traction through 2026 as interest in mitochondrial signaling and 'longevity biomarkers' has grown. Humanin is best characterized as a cytoprotective and anti-apoptotic signaling peptide: it binds and inhibits the pro-apoptotic protein BAX, preventing its translocation to the mitochondria, and it signals through a trimeric cell-surface receptor (CNTFR/WSX-1/gp130) as well as the formyl peptide receptor FPR2/FPRL1, activating pro-survival STAT3 signaling. A central theme of humanin research is its relationship with aging: circulating humanin levels decline with age in humans and several animal species, while studies have reported markedly higher humanin levels in centenarians and their offspring compared with age-matched controls, positioning it as both a candidate biomarker and a proposed driver of successful aging. Humanin also intersects with the IGF-1/insulin axis — it interacts with IGF-binding protein 3 (IGFBP-3) and is associated with lower IGF-1, a pathway repeatedly linked to extended lifespan in model organisms. Preclinical work spans neuroprotection (Alzheimer's, stroke, and optic-nerve models), metabolic effects (improved insulin sensitivity), cardioprotection, and suppression of inflammatory cytokines. A widely used synthetic analog, HNG (S14G-humanin), is roughly 1,000-fold more potent than the native peptide in neuroprotection assays and is the form used in much of the animal literature. Despite this depth of preclinical evidence, humanin remains an early-stage research compound: as of 2026 there are no completed human therapeutic trials, and like other mitochondrial-derived peptides it faces translational challenges around stability, short half-life, and delivery. It is not approved by the FDA for any indication. Also known as: HN, MT-RNR2, HNG (S14G-Humanin analog), mitochondrial-derived peptide ## Regulatory Status Not FDA-approved — investigational / research use Humanin is an endogenous mitochondrial-derived peptide with no FDA-approved therapeutic product and no completed human clinical trials as of June 2026. It is studied as a research compound only and is not on the FDA 503A Bulks List. Any human use is investigational and unapproved. Effective: June 2026 View FDA Source (https://pmc.ncbi.nlm.nih.gov/articles/PMC3705736/) ## Why Researchers Study It Humanin attracts research interest because it is an endogenous, genetically encoded signal that links mitochondrial function to whole-body aging. Its age-dependent decline, its elevation in long-lived humans, and its broad cytoprotective and anti-apoptotic activity across neuronal, metabolic, and cardiovascular models make it a compelling probe for understanding mitochondrial-to-nucleus communication and for testing whether restoring MDP signaling can influence healthspan. ## Proposed Mechanisms - Binds and inhibits the pro-apoptotic protein BAX, blocking its translocation to mitochondria and preventing programmed cell death in stressed cells - Signals through a trimeric cell-surface receptor (CNTFR/WSX-1/gp130) and the formyl peptide receptor FPR2/FPRL1 to activate pro-survival STAT3 signaling - Interacts with IGF-binding protein 3 (IGFBP-3) and is associated with reduced IGF-1, a longevity-linked pathway - Suppresses pro-inflammatory cytokines and oxidative stress, contributing to cytoprotection - Protects neurons against amyloid-beta and tau-related toxicity in preclinical Alzheimer's models ## Evidence Snapshot Low Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | In vitro / preclinical (discovery) | Neurons exposed to amyloid-beta and familial-Alzheimer's gene toxicity | Humanin (24-mer) rescued neurons from death induced by amyloid-beta and FAD mutants (APP, PS1, PS2), defining its neuroprotective activity | Source: https://www.pnas.org/doi/10.1073/pnas.98.11.6336 | | Animal (mouse) — analog HNG | S14G-humanin (HNG) neuroprotection assays | The S14G substitution increased neuroprotective potency roughly 1,000-fold versus native humanin, establishing HNG as the standard research analog | Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740898/ | | Observational (human cohort) | Centenarians and their offspring vs age-matched controls | Circulating humanin declines with age but is significantly higher in long-lived individuals, supporting its role as a longevity-associated biomarker | Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC3705736/ | | Mechanistic (PNAS) | Humanin – IGFBP-3 interaction in cell-survival assays | Humanin binds IGFBP-3 to regulate apoptosis and cell survival, linking the peptide to the IGF-1/insulin longevity axis | Source: https://www.pnas.org/doi/10.1073/pnas.2135111100 | | Review (2026) | Mitochondrial-derived peptides in healthy aging | Humanin reviewed as a regulator of lifespan and healthspan via stress resistance, metabolic, and neuroprotective signaling; translation limited by stability and delivery | Source: https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2026.1790247/full | ## Commonly Discussed Benefits Longevity: https://peptrackerpro.com/benefits/longevity Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection Metabolism: https://peptrackerpro.com/benefits/metabolism Cognition: https://peptrackerpro.com/benefits/cognition Researching Humanin? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=humanin) ## Safety & Cautions - Despite an extensive preclinical literature, there are no completed human therapeutic trials as of 2026 - Not FDA-approved for any indication; human use is investigational and unapproved - Most efficacy data come from cell and animal models, often using the synthetic HNG analog rather than native humanin - Like other mitochondrial-derived peptides, native humanin has poor stability and a short half-life, limiting clinical translation - Long-term safety in humans is unknown - Association between high humanin levels and longevity is correlational and does not establish that supplementation extends human lifespan ## Comparisons See how Humanin compares to related peptides: Humanin vs Epithalon: https://peptrackerpro.com/compare/humanin-vs-epithalon Humanin vs Klotho (Alpha-Klotho): https://peptrackerpro.com/compare/humanin-vs-klotho Humanin vs MOTS-c: https://peptrackerpro.com/compare/humanin-vs-mots-c Humanin vs NAD+: https://peptrackerpro.com/compare/humanin-vs-nad Humanin vs SS-31: https://peptrackerpro.com/compare/humanin-vs-ss-31 Humanin vs Trontinemab: https://peptrackerpro.com/compare/humanin-vs-trontinemab ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] Hashimoto Y et al. — A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. PNAS 2001 PubMed (https://www.pnas.org/doi/10.1073/pnas.98.11.6336) 2. [2] Ikonen M et al. — Interaction between humanin and IGFBP-3 regulates cell survival and apoptosis. PNAS 2003 PubMed (https://www.pnas.org/doi/10.1073/pnas.2135111100) 3. [3] Gong Z, Tas E, Muzumdar R — The emerging role of the mitochondrial-derived peptide humanin in stress resistance. PMC 2014 PubMed (https://pmc.ncbi.nlm.nih.gov/articles/PMC3705736/) 4. [4] Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives — PMC 2023 PubMed (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740898/) 5. [5] Therapeutic peptides in gerontology: mechanisms and applications for healthy aging — Frontiers in Aging 2026 PubMed (https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2026.1790247/full) 6. [6] The mitochondrial-derived peptide humanin is a regulator of lifespan and healthspan — World Mitochondria Society PubMed (https://wms-site.com/press-media/863-the-mitochondrial-derived-peptide-humanin-is-a-regulator-of-lifespan-and-healthspan) ### Keep researching in the app - Log Humanin to your private tracker - Set a dosing reminder - Compare it side-by-side with your stack Open PepTracker Pro Free: https://app.peptrackerpro.com/?add=humanin Browse more peptides: https://peptrackerpro.com/peptides ## Related Peptides ### Epithalon Low Evidence A tetrapeptide studied for its potential to activate telomerase and influence biological aging markers. Longevity: https://peptrackerpro.com/benefits/longevity Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Sleep: https://peptrackerpro.com/benefits/sleep Immune Support: https://peptrackerpro.com/benefits/immune-support View Details: https://peptrackerpro.com/peptides/epithalon \+ Compare: https://peptrackerpro.com/compare?select=epithalon Track in App: https://app.peptrackerpro.com/?add=epithalon ### Klotho (Alpha-Klotho) Low Evidence A naturally occurring longevity hormone (secreted alpha-klotho) being studied for cognition and brain aging; a single low-dose injection improved memory in aged monkeys, and a first-in-human Phase 1 trial in older adults is underway. Cognition: https://peptrackerpro.com/benefits/cognition Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Longevity: https://peptrackerpro.com/benefits/longevity View Details: https://peptrackerpro.com/peptides/klotho \+ Compare: https://peptrackerpro.com/compare?select=klotho Track in App: https://app.peptrackerpro.com/?add=klotho ### MOTS-c Low Evidence A mitochondrial-derived peptide studied for metabolic regulation, exercise mimetic effects, and longevity. Metabolism (https://peptrackerpro.com/benefits/metabolism)Fat Loss (https://peptrackerpro.com/benefits/fat-loss)Longevity (https://peptrackerpro.com/benefits/longevity)Muscle Growth (https://peptrackerpro.com/benefits/muscle-growth)+2 more View Details: https://peptrackerpro.com/peptides/mots-c \+ Compare: https://peptrackerpro.com/compare?select=mots-c Track in App: https://app.peptrackerpro.com/?add=mots-c ### NAD+ Medium Evidence A coenzyme essential for cellular energy production, studied for anti-aging and metabolic support. Energy (https://peptrackerpro.com/benefits/energy)Longevity (https://peptrackerpro.com/benefits/longevity)Anti-Aging (https://peptrackerpro.com/benefits/anti-aging)Metabolism (https://peptrackerpro.com/benefits/metabolism)+1 more View Details: https://peptrackerpro.com/peptides/nad \+ Compare: https://peptrackerpro.com/compare?select=nad Track in App: https://app.peptrackerpro.com/?add=nad ### SS-31 High Evidence A mitochondria-targeted peptide FDA-approved as FORZINITY (elamipretide) for Barth syndrome in September 2025 — the first FDA-approved mitochondrial-targeted therapeutic. Longevity: https://peptrackerpro.com/benefits/longevity Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Recovery: https://peptrackerpro.com/benefits/recovery Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection View Details: https://peptrackerpro.com/peptides/ss-31 \+ Compare: https://peptrackerpro.com/compare?select=ss-31 Track in App: https://app.peptrackerpro.com/?add=ss-31 ### Trontinemab Medium Evidence An investigational, brain-penetrant anti-amyloid antibody from Roche/Genentech that uses the proprietary 'Brainshuttle' transferrin-receptor delivery system to reach the brain far more efficiently than conventional antibodies. Trontinemab (development codes RG6102 / RO7126209) is a 2+1 bispecific molecule: it fuses the amyloid-beta-clearing antibody gantenerumab to a fragment that grabs transferrin receptor 1 (TfR1) on blood-brain-barrier cells, hitching a ride into the brain via the same receptor-mediated transport that carries iron. That shuttle lets a low intravenous dose clear amyloid plaques rapidly and deeply while triggering strikingly little of the brain swelling and micro-bleeding (ARIA) that limits approved anti-amyloid drugs. In the Phase Ib/IIa Brainshuttle AD study (NCT04639050), the 3.6 mg/kg dose removed roughly 107 centiloids of amyloid after 28 weeks, driving about 91-92% of participants below the amyloid-positivity threshold (24 centiloids) - with ARIA-E seen in fewer than 5% of participants, well below the ~13% reported for lecanemab and ~24% for donanemab. On the strength of those data, Roche launched two identical pivotal Phase 3 trials - TRONTIER 1 and TRONTIER 2 - in early symptomatic Alzheimer's disease (about 1,600 patients across 18 countries, begun in 2025), and at the 2026 Alzheimer's Association International Conference (AAIC) in London it unveiled PrevenTRON, a Phase 3 prevention trial in 1,600 cognitively unimpaired people at high risk (elevated plasma p-tau217). Trontinemab is a prescription-stage investigational biologic - it is not approved anywhere and is not a supplement or research chemical. Cognition: https://peptrackerpro.com/benefits/cognition Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection View Details: https://peptrackerpro.com/peptides/trontinemab \+ Compare: https://peptrackerpro.com/compare?select=trontinemab Track in App: https://app.peptrackerpro.com/?add=trontinemab ## Structured data ```json [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "Humanin", "description": "An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians.", "url": "https://peptrackerpro.com/peptides/humanin", "lastReviewed": "2026-06-21", "reviewedBy": { "@type": "Organization", "name": "PepTracker Pro Research Team", "url": "https://peptrackerpro.com" }, "isPartOf": { "@type": "WebSite", "name": "PepTracker Pro", "url": "https://peptrackerpro.com" } }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://peptrackerpro.com" }, { "@type": "ListItem", "position": 2, "name": "Peptides", "item": "https://peptrackerpro.com/peptides" }, { "@type": "ListItem", "position": 3, "name": "Humanin", "item": "https://peptrackerpro.com/peptides/humanin" } ] }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "People researching mitochondrial-derived peptides?", "acceptedAnswer": { "@type": "Answer", "text": "Humanin is a research peptide studied in preclinical models. An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians." } }, { "@type": "Question", "name": "Those interested in longevity biomarkers and healthy aging?", "acceptedAnswer": { "@type": "Answer", "text": "Humanin is a research peptide studied in preclinical models. An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians." } }, { "@type": "Question", "name": "Researchers studying neuroprotection in Alzheimer's and stroke models?", "acceptedAnswer": { "@type": "Answer", "text": "Humanin is a research peptide studied in preclinical models. An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians." } }, { "@type": "Question", "name": "People comparing humanin with MOTS-c and other MDPs?", "acceptedAnswer": { "@type": "Answer", "text": "Humanin is a research peptide studied in preclinical models. An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians." } }, { "@type": "Question", "name": "Those studying the IGF-1/insulin longevity pathway?", "acceptedAnswer": { "@type": "Answer", "text": "Humanin is a research peptide studied in preclinical models. An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians." } }, { "@type": "Question", "name": "Researchers exploring cellular stress resistance and apoptosis?", "acceptedAnswer": { "@type": "Answer", "text": "Humanin is a research peptide studied in preclinical models. An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians." } } ] } ] ```