Decreased Longevity and Enhancement of Age-Dependent Lesions in Mice Lacking the Nuclear Receptor Peroxisome Proliferator-Activated Receptor α (PPARα)

来自 EBSCO

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作者：

P Howroyd，C Swanson，C Dunn，R Cattley，J Corton

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摘要：

The nuclear receptor () is activated by proliferators (PP), a large class of structurally diverse chemicals, hypolipidemic drugs, and endogenous . alters the transcriptional programs of genes whose functions include , inflammation, cell fate, and stress responses in liver, heart, kidney, and skin. Many of these genes are also under control of in the absence of exogenous proliferator exposure. that lack (-null ) exhibit a number of defects in and accumulate in the liver. Here, we compared the age-dependent lesions in the liver, kidney, and heart in -null with those observed in wild-type SV129 , in the absence of exogenous chemical exposure. Groups of were sacrificed, at 6, 12, 18, 21, or 24 months of age, or allowed to age until moribund or found dead. -null had decreased longevity, due to a variety of causes. Statistically significant differences in the occurrence of a number of lesions between strains was observed. and multiple occurred in PPARa-null but not wild type . Various nonneoplastic spontaneous lesions occurred at higher incidence, shorter latency, or increased severity in -null compared with wild-type . In the liver, these included vacuolated hepatocytes and sinusoidal cells and mixed cell inflammation. The kidneys of -null exhibited higher incidences and severities of cortical mineralization. Minimal myocardial mineralization occurred at a higher incidence in -null . Our results imply that delays the of some spontaneous lesions associated with in the liver, kidney, and heart of SV129 .

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关键词：

peroxisome proliferator-activated receptor alpha peroxisome proliferator heart kidney liver aging

DOI：

10.1080/01926230490515283

被引量：

116

年份：

2004