Premature aging in vitamin D receptor mutant mice
Premature aging in vitamin D receptor mutant mice
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DOI：
10.1016/j.jsbmb.2009.03.007
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发表时间：
2009-07-01
影响因子：
4.1
通讯作者：
Tuohimaa, Pentti
中科院分区：
文献类型：
--
作者：
Keisala, Tiina;Minasyan, Anna;Tuohimaa, Pentti
Hypervitaminosis vitamin D(3) has been recently implicated in premature aging through the regulation of 1 alpha 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 (IGF1 R), 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 IGF1 R 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. (C) 2009 Elsevier Ltd. All rights reserved.
