Premature aging in vitamin D receptor mutant mice

Tiina Keisala*, Anna Minasyan, Yan Ru Lou, Jing Zou, Allan V. Kalueff, Ilmari Pyykkö, Pentti Tuohimaa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Citations (Scopus)

Abstract

Hypervitaminosis vitamin D3 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 D3 in mice is linked to aging phenomena. For this, we used vitamin D3 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 D3, our study suggests that VDR genetic ablation promotes premature aging in mice, and that vitamin D3 homeostasis regulates physiological aging.

Original languageEnglish
Pages (from-to)91-97
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume115
Issue number3-5
DOIs
Publication statusPublished - Jul 2009
Externally publishedYes

Keywords

  • Aging
  • Aging-related genes
  • Fgf-23
  • Klotho
  • Vitamin D
  • Vitamin D receptor

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