Vitamin D and aging: old concepts and new insights

Lanske, Beate; Razzaque, Mohammed S.

doi:10.1016/j.jnutbio.2007.02.002

Cited by 93 publications

(64 citation statements)

References 60 publications

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“…Altogether, these data indicate that TIF1␣ normally functions to repress the vitamin D endocrine system and additionally suggest that ectopic calcifications in TIF1␣ Ϫ/Ϫ mice are causally related to a disturbed VDR signaling pathway. Interestingly, the fact that these metabolic disturbances correlate with a calcifying arteriopathy and other features of premature aging in TIF1␣ Ϫ/Ϫ mice provides support for the hypothesis that aging is promoted by an increased activity of the vitamin D signaling pathway (26,27).…”

Section: Tif1␣ May Prevent Soft Tissue Calcifications Through Decreasmentioning

confidence: 85%

“…Thus, the scattered fibrotic glomeruli seen in TIF1␣-deficient kidneys appears to be a consequence of blocks of renal arterioles by calcified intraluminal deposits and not a cause of renal insufficiency. The normal serum phosphate levels also exclude the involvement of the circulating phosphaturic factor, fibroblast growth factor-23 (FGF-23) (26,27), in the pathogenesis of the ectopic calcifications of TIF1␣ Ϫ/Ϫ mutants.…”

Section: The Calcifying Arteriopathy Of Tif1␣ ؊/؊ Mutant Mice Resemblmentioning

confidence: 99%

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Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1α

Ignat

Teletin

Tisserand

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Calcification of arteries is a major risk factor for cardiovascular mortality in humans. Using genetic approaches, we demonstrate here that the transcriptional intermediary factor 1␣ (TIF1␣), recently shown to function as a tumor suppressor in murine hepatocytes, also participates in a molecular cascade that prevents calcifications in arterioles and medium-sized arteries. We further provide genetic evidence that this function of TIF1␣ is not exerted in hepatocytes. The sites of ectopic calcifications in mutant mice lacking TIF1␣ resemble those seen in mice carrying an activating mutation of the calcium sensor receptor (Casr) gene and, in TIF1␣-deficient kidneys, Casr expression is increased together with that of many other vitamin D receptor (VDR) direct target genes, namely Car2, Cyp24a1, Trpv5, Trpv6, Calb1, S100g, Pthlh, and Spp1. Thus, our data indicate that TIF1␣ represses the VDR pathway in kidney and suggest that an up-regulation of Casr expression in this organ could account for ectopic calcifications generated upon TIF1␣ deficiency. Interestingly, the calcifying arteriopathy of TIF1␣-null mutant mice shares features with the human age-related Mö nckeberg's disease and, overall, the TIF1␣-null mutant pathological phenotype supports the hypothesis that aging is promoted by increased activity of the vitamin D signaling pathway.aging ͉ ectopic calcification ͉ mouse knockout ͉ transcriptional regulation ͉ vitamin D signaling I nitially identified through its ability to interact directly with nuclear receptors in a ligand-dependent manner, transcriptional intermediary factor 1 (TIF1␣), also known as tripartite motif (TRIM24) protein, was subsequently described as both a negative and positive regulator of ligand-induced transactivation acting through chromatin modification (1-6).To address the physiological functions of TIF1␣, we monitored large cohorts of TIF1␣-deficient (TIF1␣ Ϫ/Ϫ ) mice. Hepatic tumors were detected at necropsy in a vast majority of TIF1␣ Ϫ/Ϫ mutants, thus indicating that TIF1␣ deficiency predisposes to liver tumor formation. Tumor predisposition was not observed in TIF1␣ Ϫ/Ϫ mutants heterozygous for the retinoic acid receptor ␣ (Rara) gene, thereby providing genetic proof that TIF1␣ and Rara act in opposition to each other in liver carcinogenesis (6).In the present study, a systematic histological analysis of TIF1␣ Ϫ/Ϫ mutants at different ages was carried out to examine the effect of TIF1␣ gene deletion on a wide range of tissues. This analysis revealed that, aside from occasional metastases from liver tumors (6), TIF1␣ Ϫ/Ϫ mutants displayed calcifications, increasing with age, in extra-hepatic connective tissues, namely arterioles, medium-sized arteries, lungs, and vibrissae. These ectopic calcifications were correlated with an increase in expression of several vitamin D direct targets, therefore raising the possibility that TIF1␣ could repress the vitamin D receptor (VDR) signaling pathway in vivo.

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Section: Tif1␣ May Prevent Soft Tissue Calcifications Through Decreasmentioning

confidence: 85%

Section: The Calcifying Arteriopathy Of Tif1␣ ؊/؊ Mutant Mice Resemblmentioning

confidence: 99%

Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1α

Ignat

Teletin

Tisserand

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…(44,45) While uncommon, these instances were attributed to the Vitamin D deficiency is prevalent among elderly persons, (35,38,46) and is a contributing risk factor for diseases such as osteoporosis and osteomalacia, which are common among the elderly. (47) Vitamin D deficiency in geriatric populations is largely due to poor nutrition and limited exposure to sunlight. (48) Many elderly patients in elderly-care facilities also have limited mobility due to illness.…”

Section: R E Su Lt Smentioning

confidence: 99%

Vitamin D deficiency remains prevalent despite increased laboratory testing in New South Wales, Australia

Quaggiotto¹,

Tran²,

Bhanugopan³

2014

smedj

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INTRODUCTIONCONCLUSION We found that vitamin D deficiency was prevalent in both men and women, with a higher prevalence in the latter, despite the substantial increased demand for 25(OH)D testing in our population over the decade. Vitamin D deficiency was associated with elevated PTH levels. Vitamin D toxicity was rare and only observed once during our study period. 25(OH)D levels decreased with age and varied with season, with the highest levels observed in late summer and the lowest in early spring.

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“…Even though the vitamin-D induced calcification in the disease state might not be comparable to the natural aging, there might be, however, similarities in the underlying mechanisms [67], as molecules involved in the mineral ion metabolism in normal and disease state are similar and a selective group of genes.…”

Section: Clinical Relevance Of In Vivo Experimental Mouse Studiesmentioning

confidence: 99%

Mineral metabolism and aging: the fibroblast growth factor 23 enigma

Lanske

Razzaque

2007

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review-Our understanding of the regulation of mineral ion homeostasis is rather stagnant, and until recently the regulation of phosphate homeostasis was thought to be a passive process mediated largely by the well known calciotrophic hormones PTH and 1,25(OH) 2 D 3 . This article summarizes the emerging trends that i) show an active regulation of phosphate homeostasis by FGF-23, a process that appears to be fairly independent of calcium homeostasis, and ii) how altered mineral ion metabolism might affect the aging process.Recent findings-A major breakthrough in FGF-23 biology has been achieved by the demonstration of strikingly similar physical and biochemical phenotypes of Fgf-23 knockout and klotho hypomorph mice, which eventually led to the identification of klotho as a cofactor in FGF-23 and its receptor interactions. A new regulatory pathway has been defined, where FGF23, in presence of klotho has shown to activate downstream signaling events, by phosphorylation of FGF receptor substrate-2α, ERK, and Egr-1. Furthermore, FGF-23 has emerged as a counter regulatory hormone that influences 1α(OH)ase and NaPi2a activities in the kidney to regulate phosphate homeostasis. Finally, studies also point towards a role of DMP1 in influencing the regulation of phosphate homeostasis, in coordination with FGF-23.Summary-Recent in vivo mouse genetic studies have expanded our understanding of the biochemical and molecular pathways involved in phosphate homeostasis, and linked FGF-23 to the genesis of such regulation. A clear understanding of the molecular interactions of essential calcium and phosphate regulating factors will enhance our understanding of the coordinated regulation of mineral ion metabolism, and will help us to redefine the molecular pathology of age-associated lesions accompanied by abnormal mineral ion metabolism, that include but are not limited to vascular calcifications, and osteoporosis.

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Vitamin D and aging: old concepts and new insights

Cited by 93 publications

References 60 publications

Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1α

Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1α

Vitamin D deficiency remains prevalent despite increased laboratory testing in New South Wales, Australia

Mineral metabolism and aging: the fibroblast growth factor 23 enigma

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