Overview
Klotho is classified as a anti-aging protein peptide. Cognitive aging reversal, kidney protection, cardiovascular protection, longevity, FGF23 regulation.
Klotho is a type-I transmembrane aging-suppressor protein expressed primarily in kidney tubular cells and brain choroid plexus. Cleaved extracellularly to generate soluble Klotho, which circulates systemically and acts as a co-receptor for FGF23, regulating phosphate and vitamin D metabolism. Also directly inhibits IGF-1 and Wnt signaling pathways that drive cellular senescence. Circulating Klotho declines dramatically with age. A single administration of soluble Klotho protein restored cognitive function in aged mice to levels of young adults within 2 weeks.
Also known as: Alpha-Klotho, KL, Soluble Klotho, Klotho protein fragment
Category
Anti-Aging Protein
Half-Life
8h
Route
IV
FDA Status
Not Approved
How Does Klotho Work?
Klotho is a type-I transmembrane aging-suppressor protein expressed primarily in kidney tubular cells and brain choroid plexus. Cleaved extracellularly to generate soluble Klotho, which circulates systemically and acts as a co-receptor for FGF23, regulating phosphate and vitamin D metabolism. Also directly inhibits IGF-1 and Wnt signaling pathways that drive cellular senescence. Circulating Klotho declines dramatically with age. A single administration of soluble Klotho protein restored cognitive function in aged mice to levels of young adults within 2 weeks.
At the molecular level, Klotho operates through pathways characteristic of the Anti-Aging Protein class, interacting with target receptors and downstream signaling cascades to produce its observed effects.
Published Research
The following studies are indexed from PubMed and peer-reviewed journals:
[1]Soluble Klotho reverses cognitive and synaptic aging
Castner et al. (Nature Aging): A single systemic injection of soluble Klotho protein significantly enhanced cognitive performance in aged nonhuman primates and mice, restoring working memory and synaptic plasticity to young-adult levels.
Evidence: preclinical[2]Low circulating Klotho is associated with cognitive decline and dementia
Semba et al.: Lower serum Klotho levels in community-dwelling adults are significantly associated with faster cognitive decline and increased dementia risk over longitudinal follow-up.
Evidence: emergingSafety Profile
⚠ EARLY-STAGE EXPERIMENTAL. Recombinant Klotho protein administration has not entered human clinical trials for anti-aging or cognitive enhancement. Klotho is a large protein (~130 kDa), not a classical peptide — reconstitution, stability, and route of administration for research use are complex. Research only.
| Side Effect | Incidence | Severity |
|---|---|---|
| Unknown in humans | Not established | rare |
Sourcing Klotho for Research
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Full Research Profile
Klotho — dosing, interactions, timelines & more
Comprehensive compound profile with sourcing information, stacking synergies, and outcome timelines.