Short-term calorie restriction protects against renal senescence of aged rats by increasing autophagic activity and reducing oxidative damage
Short-term calorie restriction protects against renal senescence of aged rats by increasing autophagic activity and reducing oxidative damage
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短期热量限制通过增加自噬活性和减少氧化损伤来防止老年大鼠的肾脏衰老
DOI：
10.1016/j.mad.2013.11.006
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发表时间：
2013-11-01
影响因子：
5.3
通讯作者：
Chen, Xiang-Mei
中科院分区：
文献类型：
--
作者：
Ning, Yi-Chun;Cai, Guang-Yan;Chen, Xiang-Mei
为探讨短期热量限制（CR）对肾脏衰老的影响，对25月龄雄性Sprague-Dawley大鼠进行为期8周的CR，其中60%的食物摄入量为随意组。短期CR的老年大鼠体重、甘油三酯水平和尿蛋白/尿肌酐比值分别较低。短期CR可使老年自由活动组肾小球体积、纤维化程度、p16蛋白表达及β-半乳糖苷酶染色阳性率降低。轻链3/Atg 8作为自噬标记物在老年肾脏中表现出显著下降，短期CR增加。p62/SQSTM 1和多聚泛素聚集体的水平在老年肾脏中增加，短期CR使其减弱。短期CR延缓了线粒体DNA氧化损伤的标志物8-羟基脱氧鸟苷的水平。此外，我们发现短期CR后老年肾脏中SIRT 1和AMPK水平升高，mTOR水平降低。这些结果表明，短期CR可以被认为是通过增加自噬和随后减少氧化损伤来延缓肾脏衰老的潜在干预措施。能量代谢的三个主要调节因子SIRT 1、AMPK和mTOR与这些效应相关。(C)2013爱思唯尔爱尔兰有限公司版权所有。
To explore the effect of short-term calorie restriction (CR) on renal aging, 8-week CR with 60% of the food intake of the ad libitum group was administered in 25-month-old male Sprague-Dawley rats. Aged rats subjected to short-term CR had lower body weight, level of triglycerides and ratio of urine protein to urine creatinine, respectively. Short-term CR blunted the increased glomerular volume, the degree of fibrosis, p16 and the positive rate of senescence-associated p-galactosidase staining of the kidneys in old ad libitum group. Light chain 3/Atg8 as an autophagy marker exhibited a marked decline in aged kidneys, which was increased by short-term CR. The levels of p62/SQSTM1 and polyubiquitin aggregates, which were increased in older kidneys, were blunted by short-term CR. Short-term CR retarded the level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage. Moreover, we found an increased level of SIRT1 and AMPK, and a decreased level of mTOR in aged kidneys after short-term CR. These results suggested that short-term CR could be considered as a potential intervention for retardation of renal senescence by increasing autophagy and subsequently reducing oxidative damage. Three master regulators of energy metabolism, SIRT1, AMPK and mTOR are associated with these effects. (C) 2013 Elsevier Ireland Ltd. All rights reserved.