Klotho
aka alpha-Klotho · KL protein · recombinant Klotho
Recombinant alpha-klotho longevity protein. Enhanced memory in aged primates.
Sequence
Mechanism of action
Anti-ageing protein hormone. Acts as an obligate co-receptor for FGF23 in phosphate/vitamin-D homeostasis and, as soluble Klotho, modulates insulin/IGF-1 and Wnt signalling and provides neuroprotective, pro-cognitive effects in models.
What the evidence actually shows
Nature Aging 2023: single injection enhanced working memory in aged primates 20%. PMID: 37400721.
Regulatory status
Dosing — what backs each figure
There is no human dosing of klotho protein. Every ClinicalTrials.gov record involving klotho is observational - measuring endogenous circulating klotho as a biomarker in kidney disease, dialysis or cardiovascular cohorts - with the sole interventional entry being an early-phase follistatin/klotho gene therapy study (NCT07285629), which is gene transfer, not protein administration. Dosing evidence is rodent only, in the 0.01-0.02 mg/kg intraperitoneal range.
Recombinant alpha-klotho protein 0.01 mg/kg or 0.02 mg/kg injected intraperitoneally one hour before LPS 10 mg/kg in a model of septic cardiorenal syndrome type 5; pretreatment significantly ameliorated acute cardiorenal injury
mouse (male 8-week-old C57BL/6) · intraperitoneal · PMID 31309036
Alpha-klotho administration reversing macrophage senescence in a diabetic retinopathy model (dose and route not stated in the abstract)
mouse · not stated in abstract · PMID 39327553
Animal doses do not convert to human doses by body weight alone. Route matters too — a compound dosed intraperitoneally in mice tells you little about subcutaneous use.
Handling and storage
Safety
References (3)
- Kuro-O M (2019) The Klotho proteins in health and disease ↗Nature Reviews NephrologyPMID 30455427DOI
Authoritative review of alpha-Klotho and beta-Klotho biology: alpha-Klotho as the obligate FGF23 co-receptor governing phosphate handling, the shed soluble ectodomain, and the accelerated-ageing phenotype of Klotho-deficient mice.
- Yuan Q, et al. (2022) A Klotho-derived peptide protects against kidney fibrosis by targeting TGF-beta signaling ↗Nature CommunicationsPMID 35064106DOI
States explicitly that because Klotho is a large transmembrane protein it is difficult to use therapeutically; screened Klotho-derived peptides and identified KP1, which binds TGF-beta receptor 2, blocks Smad2/3 activation and reduced fibrosis in mouse kidney-injury models after intravenous injection.
- Prud'homme GJ, Wang Q (2024) Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging ↗CellsPMID 39272986DOI
Review of alpha-Klotho as an anti-inflammatory and anti-senescence factor, its decline with age and chronic kidney disease, and the state of therapeutic approaches.
Data provenance
Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.
Could not verify
molecularFormula, casNumber, pubchemCid, sequence.oneLetter, sequence.threeLetter, storage.lyophilized, storage.reconstituted, storage.lightSensitive, reconstitution.solvent