Premature aging in vitamin D receptor mutant mice

J Steroid Biochem Mol Biol. 2009 Jul;115(3-5):91-7. doi: 10.1016/j.jsbmb.2009.03.007. Epub 2009 Mar 31.

Abstract

Hypervitaminosis vitamin D(3) has been recently implicated in premature aging through the regulation of 1alpha hydroxylase expression by klotho and fibroblast growth factor-23 (Fgf-23). Here we examined whether the lack of hormonal function of vitamin D(3) in mice is linked to aging phenomena. For this, we used vitamin D(3) receptor (VDR) "Tokyo" knockout (KO) mice (fed with a special rescue diet) and analyzed their growth, skin and cerebellar morphology, as well as overall motor performance. We also studied the expression of aging-related genes, such as Fgf-23, nuclear factor kappaB (NF-kappaB), p53, insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), in liver, as well as klotho in liver, kidney and prostate tissues. Overall, VDR KO mice showed several aging related phenotypes, including poorer survival, early alopecia, thickened skin, enlarged sebaceous glands and development of epidermal cysts. There was no difference either in the structure of cerebellum or in the number of Purkinje cells. Unlike the wildtype controls, VDR KO mice lose their ability to swim after 6 months of age. Expression of all the genes was lower in old VDR KO mice, but only NF-kappaB, Fgf-23, p53 and IGF1R were significantly lower. Since the phenotype of aged VDR knockout mice is similar to mouse models with hypervitaminosis D(3), our study suggests that VDR genetic ablation promotes premature aging in mice, and that vitamin D(3) homeostasis regulates physiological aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging, Premature* / genetics
  • Aging, Premature* / metabolism
  • Animals
  • Body Weight
  • Cerebellum / cytology
  • Cholecalciferol / metabolism
  • Female
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Glucuronidase / genetics
  • Glucuronidase / metabolism
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Mice
  • Mice, Knockout*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phenotype
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Calcitriol* / genetics
  • Receptors, Calcitriol* / metabolism
  • Skin / anatomy & histology
  • Skin / metabolism
  • Skin / pathology
  • Survival Rate
  • Swimming
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • NF-kappa B
  • Receptors, Calcitriol
  • Tumor Suppressor Protein p53
  • Cholecalciferol
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor I
  • fibroblast growth factor 23
  • Receptor, IGF Type 1
  • Glucuronidase
  • klotho protein