Age-related changes in the autophagic proteolysis of rat isolated liver cells: Effects of antiaging dietary restrictions
Age-related changes in the autophagic proteolysis of rat isolated liver cells: Effects of antiaging dietary restrictions
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DOI：
10.1093/gerona/56.9.b375
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发表时间：
2001-09-01
影响因子：
5.1
通讯作者：
Bergamini, E
中科院分区：
文献类型：
--
作者：
Donati, A;Cavallini, G;Bergamini, E
自噬是一种隔离和降解细胞质的细胞器和大分子成分的过程，用于细胞重组和修复，并作为早期饥饿时代谢使用的营养来源。通过监测2、6、12、18、24和27个月龄雄性SD大鼠肝细胞孵育液中Val的释放率，研究了两种对代谢有不同影响而对寿命有相似影响的抗衰老饮食方案(开始于2月龄大鼠)，即40%饮食限制(DR)和隔日随意喂养对自噬蛋白分解调节的年龄相关性变化的影响。(肝细胞在体外与添加的氨基酸和10(-7)M胰岛素或胰升糖素孵育。)随机饲喂年龄匹配的雄性SD大鼠作为对照。结果表明，在随意喂养的大鼠中，在6个月龄后，自噬蛋白的降解和氨基酸的调节呈现出与年龄相关的显著下降，而饮食抗衰老干预可以阻止这种与年龄相关的变化。比较表明，DR和隔日随意喂养对24月龄大鼠的保护作用部分不同(但两种饮食对自噬蛋白分解的有益调节作用总是相似的)。在内分泌调节方面，结果证实肝细胞对胰高血糖素的反应(但不是对胰岛素的反应)随着年龄的增长而下降，并表明抗衰老药物DRS显著提高了胰高血糖素的作用(对胰岛素的反应没有影响)。饮食、胰高血糖素(以及老年大鼠的胰岛素)和氨基酸对年龄的影响是显著的。结论：DR可显著提高肝细胞对溶酶体降解的敏感性，并可防止随着年龄的增长而衰退。提示改善肝脏自噬和溶酶体降解可能是DR抗衰老机制的一部分。
Autophagy is a process that sequesters and degrades organelles and macromolecular constituents of cytoplasm for cellular restructuring and repair and as a source of nutrients for metabolic use in early starvation. The effects of two antiaging dietary regimens (initiated in rats at the age of 2 months), namely, 40% dietary restriction (DR) and every-other-day ad-libitum feeding, that exhibited different effects on metabolism and similar effects on longevity on the age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release in the incubation medium from isolated liver cells of male albino Sprague-Dawley rats aged 2, 6, 12, 18, 24, and 27 months. (The liver cells were incubated in vitro with added amino acids and 10(-7) M insulin or glucagon.) Age-matched male albino Sprague-Dawley rats fed ad libitum served as a control. Results show that in ad-libitum-fed rats, after a transient increase by age 6 months, autophagic proteolysis and regulation by amino acid exhibit a dramatic age-related decline, and that the age-related changes are prevented by dietary antiaging intervention. A comparison shows that the protective effects of DR and every-other-day ad-libitum feeding are partially different in 24-month-old rats (but the beneficial effects of the two diets on regulation of autophagic proteolysis are always similar). With regard to endocrine regulation, results confirm that the liver cell response to glucagon (but not to insulin) declines with increasing age, and they show that antiaging DRs significantly improve the effects of glucagon (and have no effect on the response to insulin). The interactions of age by diet, glucagon (and in older rats, insulin), and amino acids are significant. It is concluded that DR significantly improves the susceptibility of liver cells to lysosomal degradation, and it prevents decline with increasing age. It is suggested that improved liver autophagy and lysosomal degradation might be part of the antiaging mechanisms of DR.