--- title: "Klotho (Alpha-Klotho) | PepTracker Pro" url: https://peptrackerpro.com/peptides/klotho description: "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." 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) # 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. Aliases alpha-klotho +7 more Evidence Low Evidence Last Updated 2026-06-21 Reading Time 4 min ## What It Is Klotho is a longevity protein the body makes naturally, named after the Greek Fate who spins the thread of life. The form most studied for brain aging is alpha-klotho (α-klotho), a hormone that is cleaved from a membrane-bound protein in the kidney and brain and released into the blood and cerebrospinal fluid, where it influences insulin, fibroblast growth factor (FGF), Wnt, and NMDA-receptor signaling. People who naturally carry the KL-VS genetic variant tend to have higher klotho levels and, on average, perform better on tests of memory and thinking, which is what first drew researchers to klotho as a target for healthy brain aging. In animals, raising klotho — genetically or by injecting the protein — improves synaptic plasticity, learning, and memory and adds resilience in models of Alzheimer's and Parkinson's disease. The landmark finding came in 2023, when a single low-dose (but, notably, not high-dose) injection of klotho enhanced memory in aged rhesus monkeys for up to about two weeks — even though klotho does not appear to cross the blood-brain barrier, implying it works through an indirect, downstream cascade rather than entering the brain directly. A 2025 meta-analysis of roughly 6,600 people reported a positive association between circulating klotho levels and cognitive performance. On the strength of this work, a UCSF team led by Dr. Dena Dubal has been moving a Phase 1 clinical trial forward to test whether a single low-dose injection of klotho can improve cognition in healthy older adults. Important context: klotho is a large protein, not a small synthetic peptide, and delivering it as a drug is technically difficult; it is investigational, is not approved by the FDA or any regulator, and is not a marketed, prescribed, or compounded product. Despite intense online interest, the klotho studied in these trials is not the same thing as the 'klotho' supplements or research chemicals sometimes sold to consumers. Also known as: alpha-klotho, α-klotho, secreted klotho, soluble klotho, KL protein, klotho protein, longevity hormone klotho, s-klotho ## Why Researchers Study It Klotho is one of the most compelling targets in the science of brain aging because it links a natural longevity hormone to measurable differences in human cognition. People with higher klotho (including KL-VS variant carriers) tend to think and remember better, and in animals a single klotho injection can restore learning and memory even in old or disease-model brains — apparently without the protein entering the brain at all. Researchers want to know whether giving klotho to humans can replicate that benefit, how a peripherally injected protein produces central effects, and whether klotho could one day protect against age-related cognitive decline, Alzheimer's, or Parkinson's. It represents a fundamentally different approach from the metabolic (GLP-1/amylin) and tissue-repair peptides that dominate the field: a longevity-and-cognition mechanism rather than a weight or recovery one. ## Proposed Mechanisms - Circulates as a secreted hormone (alpha-klotho) after cleavage from a membrane-bound protein, acting on distant tissues including the brain - Enhances synaptic plasticity and cognition through GluN2B-dependent NMDA-receptor signaling - Modulates FGF23/FGF, insulin/IGF-1, and Wnt signaling pathways involved in aging - Appears to act without crossing the blood-brain barrier, implying an indirect, downstream cascade rather than direct brain entry - May modify APOE-associated Alzheimer's risk and add resilience to neurodegenerative stress in animal models ## Evidence Snapshot Low Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | Human (Phase 1, in progress) | First-in-human trial (UCSF, Dr. Dena Dubal) testing a single low-dose klotho injection for cognition in healthy older adults; cognitive testing over ~90 days | Designed to test whether exogenous klotho improves cognition; no efficacy results published yet | Source: https://www.med.upenn.edu/aging/klotho.html | | Animal (non-human primate) | Aged rhesus macaques given a single injection of klotho (low vs high dose) | A single LOW dose (not high dose) enhanced memory for up to ~2 weeks despite klotho not crossing the blood-brain barrier | Source: https://www.nature.com/articles/s43587-023-00441-x | | Human (observational meta-analysis) | ~6,600 subjects pooled across studies (2025) | Positive association between circulating klotho levels and cognitive performance (correlational, not causal) | Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574126/ | | Animal (rodent) | Mice injected with klotho, including aged and neurodegeneration models | Improved synaptic plasticity, spatial memory, and resilience; benefits from a single injection lasting weeks | Source: https://www.med.upenn.edu/aging/klotho.html | ## Commonly Discussed Benefits 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 Researching Klotho (Alpha-Klotho)? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=klotho) ## Safety & Cautions - Investigational only — klotho is NOT approved by the FDA or any regulator for any use, and is not a marketed, prescribed, or compounded product - Most evidence is from animals (mice and monkeys); the human Phase 1 trial is early and has no published efficacy results - Klotho is a large protein, not a small synthetic peptide — it is hard to deliver as a drug and does not readily cross the blood-brain barrier - In the monkey study, only the LOW dose helped and the HIGH dose did not — 'more' is not better, and human dosing is unknown - Cognitive improvement is notoriously hard to measure in short trials, and animal results often fail to translate to humans - Klotho affects the kidneys, mineral metabolism, and cardiovascular system; safety beyond cognition requires careful monitoring - 'Klotho' products, peptides, or supplements sold online are not the clinical-grade protein being studied and are not a validated way to raise klotho or improve cognition ## Comparisons See how Klotho (Alpha-Klotho) compares to related peptides: Klotho (Alpha-Klotho) vs Cerebrolysin: https://peptrackerpro.com/compare/klotho-vs-cerebrolysin Klotho (Alpha-Klotho) vs Dihexa: https://peptrackerpro.com/compare/klotho-vs-dihexa Klotho (Alpha-Klotho) vs Epithalon: https://peptrackerpro.com/compare/klotho-vs-epithalon Klotho (Alpha-Klotho) vs FOXO4-DRI: https://peptrackerpro.com/compare/klotho-vs-foxo4-dri Klotho (Alpha-Klotho) vs Humanin: https://peptrackerpro.com/compare/klotho-vs-humanin Klotho (Alpha-Klotho) vs MOTS-c: https://peptrackerpro.com/compare/klotho-vs-mots-c Klotho (Alpha-Klotho) vs NAD+: https://peptrackerpro.com/compare/klotho-vs-nad Klotho (Alpha-Klotho) vs Trontinemab: https://peptrackerpro.com/compare/klotho-vs-trontinemab ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] Castner et al. — Longevity factor klotho enhances cognition in aged nonhuman primates (Nature Aging, 2023) PubMed (https://www.nature.com/articles/s43587-023-00441-x) 2. [2] Is Klotho the key to brain resilience in aging? — Institute on Aging, University of Pennsylvania PubMed (https://www.med.upenn.edu/aging/klotho.html) 3. [3] KLOTHO-VS heterozygosity, α-klotho protein levels and cognitive performance (PMC, 2025) PubMed (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574126/) ### Keep researching in the app - Log Klotho (Alpha-Klotho) 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=klotho Browse more peptides: https://peptrackerpro.com/peptides ## Related Peptides ### Cerebrolysin Medium Evidence A porcine brain-derived peptide mixture approved in some countries for stroke recovery and neurodegenerative conditions. Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection Cognition: https://peptrackerpro.com/benefits/cognition Recovery: https://peptrackerpro.com/benefits/recovery View Details: https://peptrackerpro.com/peptides/cerebrolysin \+ Compare: https://peptrackerpro.com/compare?select=cerebrolysin Track in App: https://app.peptrackerpro.com/?add=cerebrolysin ### Dihexa Low Evidence A hexapeptide analog studied for cognitive enhancement via hepatocyte growth factor pathway activation. Cognition: https://peptrackerpro.com/benefits/cognition Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection Anti-Aging: https://peptrackerpro.com/benefits/anti-aging View Details: https://peptrackerpro.com/peptides/dihexa \+ Compare: https://peptrackerpro.com/compare?select=dihexa Track in App: https://app.peptrackerpro.com/?add=dihexa ### 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 ### FOXO4-DRI Low Evidence A senolytic peptide designed to selectively clear senescent cells by disrupting FOXO4-p53 interaction. Longevity: https://peptrackerpro.com/benefits/longevity Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Skin: https://peptrackerpro.com/benefits/skin View Details: https://peptrackerpro.com/peptides/foxo4-dri \+ Compare: https://peptrackerpro.com/compare?select=foxo4-dri Track in App: https://app.peptrackerpro.com/?add=foxo4-dri ### 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. 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)+1 more View Details: https://peptrackerpro.com/peptides/humanin \+ Compare: https://peptrackerpro.com/compare?select=humanin Track in App: https://app.peptrackerpro.com/?add=humanin ### 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 ### 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": "Klotho (Alpha-Klotho)", "description": "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.", "url": "https://peptrackerpro.com/peptides/klotho", "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": "Klotho (Alpha-Klotho)", "item": "https://peptrackerpro.com/peptides/klotho" } ] }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "People following longevity and brain-aging research who have heard klotho can 'reverse brain aging'?", "acceptedAnswer": { "@type": "Answer", "text": "Klotho (Alpha-Klotho) is a research peptide studied in preclinical models. 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