Premature aging in vitamin D receptor mutant mice |
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Authors: | Tiina Keisala Anna Minasyan Yan-Ru Lou Jing Zou Allan V Kalueff Ilmari Pyykk Pentti Tuohimaa |
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Institution: | aDepartment of Anatomy, Medical School, University of Tampere, Tampere 33014, Finland;bDepartment of Otolaryngology, Medical School, University of Tampere, Tampere, Finland;cDepartment of Physiology and Biophysics, Medical School, Georgetown University, Washington, DC, USA;dDepartment of Pharmacology, Tulane University Medical School, New Orleans, LA, USA;eDepartment of Clinical Chemistry, Tampere University Hospital, Tampere, Finland |
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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. |
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Keywords: | Vitamin D Aging Fgf-23 Klotho Vitamin D receptor Aging-related genes |
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