Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process.

Authors: Razzaque MS; Sitara D; Taguchi T; St-Arnaud R; Lanske B

Abstract: 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.

Keywords: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics/metabolism; Aging, Premature/*metabolism; Animals; Atherosclerosis; Cell Proliferation; Fibroblast Growth Factors/*deficiency/genetics/*metabolism; Gene Deletion; Gene Expression Regulation; Glucuronidase/genetics/metabolism; Intestines/metabolism; Lung/metabolism; Lymphatic System/metabolism; Mice; Phenotype; Skin/metabolism; T-Lymphocytes/metabolism; Vitamin D/*metabolism
Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume: 20
Issue: 6
Pages: 720-2
Date: Jan. 27, 2006
PMID: 16436465
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Citation:

Razzaque MS, Sitara D, Taguchi T, St-Arnaud R, Lanske B (2006) Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20: 720-2.


Study Lifespan Factors:
  • Fgf23 Fibroblast growth factor 23


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