ID 112398
Author
Watanabe, Ryuichi Keio University
Fujita, Nobuyuki Keio University
Sato, Yuiko Keio University
Kobayashi, Tami Keio University
Morita, Mayu Keio University
Oike, Takatsugu Keio University
Miyamoto, Kana Keio University
Kuro-o, Makoto Jichi Medical University
Michigami, Toshimi Osaka Medical Center and Research Institute for Maternal and Child Health
Tsuji, Takashi Keio University
Toyama, Yoshiaki Keio University
Nakamura, Masaya Keio University
Matsumoto, Morio Keio University
Miyamoto, Takeshi Keio University
Content Type
Journal Article
Description
Control of phosphate metabolism is crucial to regulate aging in mammals. Klotho is a well-known anti-aging factor that regulates phosphate metabolism: mice mutant or deficient in Klotho exhibit phenotypes resembling human aging. Here we show that ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) is required for Klotho expression under phosphate overload conditions. Loss-of-function Enpp1 ttw/ttw mice under phosphate overload conditions exhibited phenotypes resembling human aging and Klotho mutants, such as short life span, arteriosclerosis and osteoporosis, with elevated serum 1,25(OH)2D3 levels. Enpp1ttw/ttw mice also exhibited significantly reduced renal Klotho expression under phosphate overload conditions, and aging phenotypes in these mice were rescued by Klotho overexpression, a low vitamin D diet or vitamin D receptor knockout. These findings indicate that Enpp1 plays a crucial role in regulating aging via Klotho expression under phosphate overload conditions.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
7
Start Page
7786
Published Date
2017-08-10
Remark
Supplementary Figures : srep_7_7786_s1.pdf
Rights
© The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences