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

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/phosphodieste...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c77c7732b79d4a609173952fd4dd9dc8
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spelling	oai:doaj.org-article:c77c7732b79d4a609173952fd4dd9dc82021-12-02T12:32:46ZEnpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions10.1038/s41598-017-07341-22045-2322https://doaj.org/article/c77c7732b79d4a609173952fd4dd9dc82017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07341-2https://doaj.org/toc/2045-2322Abstract 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. Enpp1 ttw/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.Ryuichi WatanabeNobuyuki FujitaYuiko SatoTami KobayashiMayu MoritaTakatsugu OikeKana MiyamotoMakoto Kuro-oToshimi MichigamiSeiji FukumotoTakashi TsujiYoshiaki ToyamaMasaya NakamuraMorio MatsumotoTakeshi MiyamotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions
description	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 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. Enpp1 ttw/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.
format	article
author	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
author_facet	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
author_sort	Ryuichi Watanabe
title	Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions
title_short	Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions
title_full	Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions
title_fullStr	Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions
title_full_unstemmed	Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions
title_sort	enpp1 is an anti-aging factor that regulates klotho under phosphate overload conditions
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c77c7732b79d4a609173952fd4dd9dc8
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Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions

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