Scientific Reports (Aug 2017)

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

DOI
https://doi.org/10.1038/s41598-017-07341-2
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 12

Abstract

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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 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.