Vitamin D and the Klotho Gene

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FASEB J. 2006 Jan 25; [Epub ahead of print]

Premature aging-like phenotype in fibroblast growth

factor 23 null mice is a vitamin D-mediated process.

Razzaque MS, Sitara D, Taguchi T, St-Arnaud R, Lanske

B.

Fibroblast growth factor 23 null mice (Fgf-23(-/-))

have a short lifespan and show numerous biochemical

and morphological features consistent with premature

aging-like phenotypes, including kyphosis, severe

muscle wasting, hypogonadism, osteopenia, emphysema,

uncoordinated movement, T cell dysregulation, and

atrophy of the intestinal villi, skin, thymus, and

spleen. Furthermore, increased vitamin D activities in

homozygous mutants are associated with severe

atherosclerosis and widespread soft tissue

calcifications; ablation of vitamin D activity from

Fgf-23(-/- )mice, by genetically deleting the

1alpha(OH)ase gene, eliminates atherosclerosis and

ectopic calcifications and significantly rescues

premature aging-like features of Fgf-23(-/- )mice,

resulting in prolonged survival of

Fgf-23(-/-)/1alpha(OH)ase(-/- )double mutants. Our

results indicate a novel role of Fgf-23 in developing

premature aging-like features through regulating

vitamin D homeostasis. Finally, our data support a new

model of interactions among Fgf-23, vitamin D, and

klotho, a gene described as being associated with

premature aging process.

PMID: 16436465 [PubMed - as supplied by publisher]

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