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ID 112398
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
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
Springer Nature
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Supplementary Figures : srep_7_7786_s1.pdf
© The Author(s) 2017
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Institute of Advanced Medical Sciences