Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions

Ryuichi Watanabe, Nobuyuki Fujita, Yuiko Sato, Tami Kobayashi, Mayu Morita, Takatsugu Oike, Kana Miyamoto, Makoto Kuro-o, Toshimi Michigami, Seiji Fukumoto, Takashi Tsuji, Yoshiaki Toyama, Masaya Nakamura, Morio Matsumoto, Takeshi Miyamoto

研究成果: Article

6 引用 (Scopus)

抄録

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 Enpp1ttw/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.

元の言語English
記事番号7786
ジャーナルScientific reports
7
発行部数1
DOI
出版物ステータスPublished - 01-12-2017

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Phosphates
Phenotype
Calcitriol Receptors
Arteriosclerosis
Vitamin D
Osteoporosis
ectonucleotide pyrophosphatase phosphodiesterase 1
Mammals
Diet
Kidney
Serum

All Science Journal Classification (ASJC) codes

  • General

これを引用

Watanabe, R., Fujita, N., Sato, Y., Kobayashi, T., Morita, M., Oike, T., ... Miyamoto, T. (2017). Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions. Scientific reports, 7(1), [7786]. https://doi.org/10.1038/s41598-017-07341-2
Watanabe, Ryuichi ; Fujita, Nobuyuki ; Sato, Yuiko ; Kobayashi, Tami ; Morita, Mayu ; Oike, Takatsugu ; Miyamoto, Kana ; Kuro-o, Makoto ; Michigami, Toshimi ; Fukumoto, Seiji ; Tsuji, Takashi ; Toyama, Yoshiaki ; Nakamura, Masaya ; Matsumoto, Morio ; Miyamoto, Takeshi. / Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions. :: Scientific reports. 2017 ; 巻 7, 番号 1.
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abstract = "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 Enpp1ttw/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.",
author = "Ryuichi Watanabe and Nobuyuki Fujita and Yuiko Sato and Tami Kobayashi and Mayu Morita and Takatsugu Oike and Kana Miyamoto and Makoto Kuro-o and Toshimi Michigami and Seiji Fukumoto and Takashi Tsuji and Yoshiaki Toyama and Masaya Nakamura and Morio Matsumoto and Takeshi Miyamoto",
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Watanabe, R, Fujita, N, Sato, Y, Kobayashi, T, Morita, M, Oike, T, Miyamoto, K, Kuro-o, M, Michigami, T, Fukumoto, S, Tsuji, T, Toyama, Y, Nakamura, M, Matsumoto, M & Miyamoto, T 2017, 'Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions', Scientific reports, 巻. 7, 番号 1, 7786. https://doi.org/10.1038/s41598-017-07341-2

Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions. / Watanabe, Ryuichi; Fujita, Nobuyuki; Sato, Yuiko; Kobayashi, Tami; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Kuro-o, Makoto; Michigami, Toshimi; Fukumoto, Seiji; Tsuji, Takashi; Toyama, Yoshiaki; Nakamura, Masaya; Matsumoto, Morio; Miyamoto, Takeshi.

:: Scientific reports, 巻 7, 番号 1, 7786, 01.12.2017.

研究成果: Article

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AU - Watanabe, Ryuichi

AU - Fujita, Nobuyuki

AU - Sato, Yuiko

AU - Kobayashi, Tami

AU - Morita, Mayu

AU - Oike, Takatsugu

AU - Miyamoto, Kana

AU - Kuro-o, Makoto

AU - Michigami, Toshimi

AU - Fukumoto, Seiji

AU - Tsuji, Takashi

AU - Toyama, Yoshiaki

AU - Nakamura, Masaya

AU - Matsumoto, Morio

AU - Miyamoto, Takeshi

PY - 2017/12/1

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N2 - 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 Enpp1ttw/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.

AB - 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 Enpp1ttw/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.

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