HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/F1177    most recent 00038.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by van Abel, M. Articles by Bindels, R. J. M. Search for Related Content PubMed PubMed Citation Articles by van Abel, M. Articles by Bindels, R. J. M.

Age-dependent alterations in Ca²⁺ homeostasis: role of TRPV5 and TRPV6

¹Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen; and ²Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands

Submitted 1 February 2006 ; accepted in final form 8 May 2006

Aging is associated with alterations in Ca²⁺ homeostasis, which predisposes elder people to hyperparathyroidism and osteoporosis. Intestinal Ca²⁺ absorption decreases with aging and, in particular, active transport of Ca²⁺ by the duodenum. In addition, there are age-related changes in renal Ca²⁺ handling. To examine age-related changes in expression of the renal and intestinal epithelial Ca²⁺ channels, control (TRPV5^+/+) and TRPV5 knockout (TRPV5^–/–) mice aged 10, 30, and 52 wk were studied. Aging of TRPV5^+/+ mice resulted in a tendency toward increased renal Ca²⁺ excretion and significantly decreased intestinal Ca²⁺ absorption, which was accompanied by reduced expression of TRPV5 and TRPV6, respectively, despite increased serum 1,25(OH)₂D₃ levels. Similarly, in TRPV5^–/– mice the existing renal Ca²⁺ loss was more pronounced in elder animals, whereas the compensatory intestinal Ca²⁺ absorption and TRPV6 expression declined with aging. In both mice strains, aging resulted in a resistance to 1,25(OH)₂D₃ and diminished renal vitamin D receptor mRNA levels, whereas serum Ca²⁺ levels remained constant. Furthermore, 52-wk-old TRPV5^–/– mice showed severe hyperparathyroidism, whereas PTH levels in elder TRPV5^+/+ mice remained normal. In 52-wk-old TRPV5^–/– mice, serum osteocalcin levels were increased in accordance with the elevated PTH levels, suggesting an increased bone turnover in these mice. In conclusion, downregulation of TRPV5 and TRPV6 is likely involved in the impaired Ca²⁺ (re)absorption during aging. Moreover, TRPV5^–/– mice likely develop age-related hyperparathyroidism and osteoporotic characteristics before TRPV5^+/+ mice, demonstrating the importance of the epithelial Ca²⁺ channels in Ca²⁺ homeostasis.

ECaC; CaT1; VDR; PTH; 1,25(OH)₂D₃; aging; osteoporosis

This article has been cited by other articles:

				M. G. Tordoff Taste Solution Preferences of C57BL/6J and 129X1/SvJ Mice: Influence of Age, Sex, and Diet Chem Senses, September 1, 2007; 32(7): 655 - 671. [Abstract] [Full Text] [PDF]

				B. Nilius, G. Owsianik, T. Voets, and J. A. Peters Transient Receptor Potential Cation Channels in Disease Physiol Rev, January 1, 2007; 87(1): 165 - 217. [Abstract] [Full Text] [PDF]