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/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.

• Authors: 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
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 7786 (08 10 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28798354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphates
• Phosphoric Diester Hydrolases
• ectonucleotide pyrophosphatase phosphodiesterase 1
• Glucuronidase
• Klotho Proteins
• Pyrophosphatases
• Calcitriol

Topics

• Aging (metabolism, pathology)
• Animals
• Bone Density
• Calcitriol (blood)
• Glucuronidase (genetics, metabolism)
• Klotho Proteins
• Loss of Function Mutation
• Mice
• Phosphates (metabolism)
• Phosphoric Diester Hydrolases (genetics, metabolism)
• Pyrophosphatases (genetics, metabolism)