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

FASEB J. 2006 Apr;20(6):720-2. doi: 10.1096/fj.05-5432fje. Epub 2006 Jan 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Aging, Premature / metabolism*
  • Animals
  • Atherosclerosis
  • Cell Proliferation
  • Fibroblast Growth Factors / deficiency*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Gene Deletion
  • Gene Expression Regulation
  • Glucuronidase / genetics
  • Glucuronidase / metabolism
  • Intestinal Mucosa / metabolism
  • Lung / metabolism
  • Lymphatic System / metabolism
  • Mice
  • Phenotype
  • Skin / metabolism
  • T-Lymphocytes / metabolism
  • Vitamin D / metabolism*

Substances

  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Glucuronidase
  • klotho protein