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. 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
-
- Scientific Reports
-
Scientific Reports 7 7786-, 2017-08-10
Springer Nature
- Tweet
Details 詳細情報について
-
- CRID
- 1050564287756266112
-
- NII Article ID
- 120006535028
-
- ISSN
- 20452322
-
- Text Lang
- en
-
- Article Type
- journal article
-
- Data Source
-
- IRDB
- CiNii Articles