Cognitive & neuroEvidence B3 cited

Klotho

aka alpha-Klotho · KL protein · recombinant Klotho

Recombinant alpha-klotho longevity protein. Enhanced memory in aged primates.

Molecular wt
116181g/mol

Sequence

Read this before quoting the sequence
Klotho is a large glycoprotein, not a synthetic vial peptide, and the full sequence is not reproduced here. Human alpha-Klotho: UniProt Q9UEF7 (KLOT_HUMAN), 1012 amino acids, single-pass type I membrane protein, UniProt-computed mass 116,181 Da for the unmodified precursor; the sequence begins MPASAPPRRPRPPPPSLSLLLVLLGLGGRRLRAEPGDGAQTWARFSRPPAPEAAG. The extracellular domain is shed to give circulating 'soluble Klotho'; FDA GSRS registers KLOTHO SECRETED PEPTIDE (UNII D1YO7772E1) as a 516-residue secreted form beginning EPGDGAQTWARFSRPPAPEAAG. Beta-Klotho (KLB, the FGF21 co-receptor) is a different protein (FDA GSRS BETA-KLOTHO, 1044 aa) and should not be conflated with alpha-Klotho. There is no single defined 'Klotho peptide' product.
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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

Grade B

Nature Aging 2023: single injection enhanced working memory in aged primates 20%. PMID: 37400721.

Regulatory status

Status
Not a medicine anywhere. No Klotho protein product has a marketing authorisation, and no IND-stage recombinant Klotho drug product was identified. Klotho appears in ClinicalTrials.gov almost exclusively as a measured biomarker in observational studies (e.g. NCT05777954, NCT03173235, NCT03858413), not as an administered intervention.
Clinical stage
No interventional clinical development of Klotho protein as a therapeutic was identified; preclinical only (including Klotho-derived peptides such as KP1, which are distinct compounds).
WADA
Not named on the 2026 WADA Prohibited List. Note S2.3 covers 'other growth factors or growth factor modulators affecting muscle, tendon or ligament protein synthesis/degradation, vascularisation, energy utilization, regenerative capacity or fibre type switching', which is a broad catch-all.
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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.

PreclinicalAnimal studies — not a human dose
  • 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.

No established human dose
No approved label or completed human trial establishes a dosing regimen for this compound. Anything presented as a standard protocol for it — anywhere — is someone's convention rather than a finding.

Handling and storage

No compound-specific stability data exists
Not applicable in the usual sense. Klotho is a large glycosylated protein with no approved or investigational human drug product, so no storage specification exists anywhere in regulatory or pharmacopoeial sources. Any storage guidance circulating for 'Klotho' refers to research-grade recombinant protein preparations from individual suppliers, which are lot- and supplier-specific and are not a property of the compound. General peptide handling still applies — reconstitute gently, keep it cold, keep it dark — but any specific figure you see quoted for this compound elsewhere is someone's assumption, not a measurement.

Safety

References (3)

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

Research use only
This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.