Adult-onset calorie restriction delays the accumulation of mitochondrial enzyme abnormalities in aging rat kidney tubular epithelial cells
Adult-onset calorie restriction delays the accumulation of mitochondrial enzyme abnormalities in aging rat kidney tubular epithelial cells
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DOI：
10.1152/ajprenal.00307.2006
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Aiken, Judd M.
中科院分区：
文献类型：
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作者：
McKiernan, Susan H.;Tuen, Victoria C.;Aiken, Judd M.
成人起始卡路里限制（A-CR）是一种延长寿命和健康衰老的实验模型，与早期开始的卡路里限制相比，探索较少，但对人类应用更现实。我们研究了A-CR对衰老大鼠肾脏的影响，包括常见的结构性年龄依赖性变化和肾小管上皮细胞线粒体酶异常的积累。在Fischer x Brown Norway大鼠肾脏发生显著的年龄相关变化之前，在中年大鼠中开始40%的热量限制。与年龄匹配的自由进食大鼠相比，这种饮食干预在6个月内有效地减少了肾小球硬化和肾小管萎缩，在1年内改变了间质纤维化形成的速率，在18个月内改变了血管壁增厚和表达细胞色素c氧化酶（考克斯）缺陷的肾小管上皮细胞。我们的组织学方法（组织化学染色的线粒体酶活性和激光捕获显微切割）加上线粒体DNA（mtDNA）PCR分析表明，COX-缺陷型肾小管上皮细胞积累mtDNA缺失突变，这些细胞含有独特的，克隆扩增的mtDNA缺失突变。线粒体异常的肾小管上皮细胞呈现出生理功能障碍的细胞特征。
Adult-onset calorie restriction (A-CR) is an experimental model of life extension and healthy aging less explored, compared with calorie restriction begun at early ages, but one more realistic for human application. We examined the effect of A-CR on the aging rat kidney with respect to common structural age-dependent changes and the accumulation of mitochondrial enzyme abnormalities in tubular epithelial cells. A 40% calorie restriction was initiated in middle-aged rats, before the onset of significant age-related changes in the Fischer x Brown Norway rat kidney. This dietary intervention effectively reduced glomerulosclerosis and tubular atrophy within 6 mo and changed the rate of interstitial fibrosis formation within 1 yr and vascular wall thickening and the expression cytochrome c oxidase (COX)-deficient tubular epithelial cells in 18 mo compared with age-matched ad libitum-fed rats. Our histological approach (histochemical staining for mitochondrial enzyme activity and laser capture microdissection) coupled with mitochondrial DNA (mtDNA) PCR analyses demonstrated that COX-deficient renal tubular epithelial cells accumulated mtDNA deletion mutations and that these cells contained unique, clonally expanded mtDNA deletion mutations. Renal tubular epithelial cells with mitochondrial abnormalities presented cellular characteristics indicative of physiological dysfunction.