Dietary phosphate modifies lifespan in Drosophila

被引:14
作者
Bergwitz, Clemens [1 ]
机构
[1] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA
关键词
CKD; drosophila; hyperphosphatemia; lifespan; phosphate metabolism; CHRONIC KIDNEY-DISEASE; SACCHAROMYCES-CEREVISIAE; INORGANIC POLYPHOSPHATE; VASCULAR CALCIFICATION; HYPERTROPHIC CHONDROCYTES; ARTERY CALCIFICATION; PARATHYROID-HORMONE; MINERAL METABOLISM; INDUCED APOPTOSIS; PTH SECRETION;
D O I
10.1093/ndt/gfs362
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Phosphate is required for many important cellular processes and having too little phosphate (hypophosphatemia) or too much (hyperphosphatemia) can cause disease and reduce lifespan in humans. Drosophila melanogaster has been a powerful tool to discover evolutionarily well-conserved nutrient-sensing pathways that are important for the lifespan extension. We have established Drosophila as a model system for studying the effects of dietary phosphate during development and adult life. When absorption of phosphate is blocked by sevelamer or cellular uptake is inhibited by phosphonoformic acid (PFA), larval development is delayed in a phosphate-dependent fashion. Conversely, restriction of phosphate absorption with sevelamer or reduced cellular uptake after treatment with PFA is able to extend the adult lifespan of otherwise normal flies. Gaining an understanding of the specific pathways and mediators that regulate cellular and organismic phosphate levels might ultimately lead to the development of improved dietary and therapeutic approaches to the treatment of human disorders of hypo- and hyperphosphatemia.
引用
收藏
页码:3399 / 3406
页数:8
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