ArticleThe Journal of biological chemistry2013
Biochemical and functional characterization of the klotho-VS polymorphism implicated in aging and disease risk.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Impact of Klotho genotype on lactylation in Alzheimer's disease and mechanistic insights.Immunity & ageing : I & A · 2026Article
- Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.Scientific reports · 2025Article
- Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.bioRxiv : the preprint server for biology · 2024Article
- Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden.JAMA network open · 2022Article
- Circulating Klotho Is Higher in Cerebrospinal Fluid than Serum and Elevated Among KLOTHO Heterozygotes in a Cohort with Risk for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Article
- Exploiting the neuroprotective effects of α-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction.Neuronal signaling · 2021Review
- FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- PTSD and the klotho longevity gene: Evaluation of longitudinal effects on inflammation via DNA methylation.Psychoneuroendocrinology · 2020Article
- A new potential mode of cardiorenal protection of KLOTHO gene variability in type 1 diabetic adolescents.Journal of molecular medicine (Berlin, Germany) · 2020Article
- The association between Single Nucleotide Polymorphisms of Klotho Gene and Mortality in Elderly Men: The MrOS Sweden Study.Scientific reports · 2020Article
- Klotho: An Elephant in Aging Research.The journals of gerontology. Series A, Biological sciences and medical sciences · 2019Review
- Klotho, the Key to Healthy Brain Aging?Brain plasticity (Amsterdam, Netherlands) · 2018Review
- FGF23 Actions on Target Tissues-With and Without Klotho.Frontiers in endocrinology · 2018Review
- Human alternative Klotho mRNA is a nonsense-mediated mRNA decay target inefficiently spliced in renal disease.JCI insight · 2017Article
- Modeled structural basis for the recognition of α2-3-sialyllactose by soluble Klotho.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.Brain imaging and behavior · 2017Article
- Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- New Insights into the Mechanism of Action of Soluble Klotho.Frontiers in endocrinology · 2017Review
- The Anti-Aging Protein Klotho Enhances Remyelination Following Cuprizone-Induced Demyelination.Journal of molecular neuroscience : MN · 2015Article
- Variation in longevity gene KLOTHO is associated with greater cortical volumes.Annals of clinical and translational neurology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Klotho (KL) is an age-regulating protein named after the Greek goddess who spins the thread of life. Mice deficient in KL are normal throughout development, but rapidly degenerate and display a variety of aging-associated abnormalities that eventually lead to decreased life expectancy. While multiple genetic association studies have identified KL polymorphisms linked with changes in disease risk, there is a paucity of concrete mechanistic data to explain how these amino acid substitutions alter KL protein function. The KLVS polymorphism is suggested to lead to changes in protein trafficking although the mechanism is unclear. Our studies have sought to further investigate the functional differences in the KLVS variant that result in increased risk of many age-related diseases. Our findings suggest that the F352V and C370S substitutions lead to alterations in processing as seen by differences in shedding and half-life. Their co-expression in KLVS results in a phenotype resembling wild-type, but despite this intragenic complementation there are still changes in homodimerization and interactions with FGFR1c. Taken together, these studies suggest that KLVS leads to altered homodimerization that indirectly leads to changes in processing and FGFR1c interactions. These findings help elucidate the functional differences that result from the VS polymorphism, which will help clarify how alterations in KL function can lead to human disease and affect cognition and lifespan.
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Registered trials
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