Bile Acids, Chaperones, and Mammalian Longevity
Bile Acids, Chaperones, and Mammalian Longevity
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DOI：
10.1089/rej.2011.1286
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发表时间：
2012-04-01
影响因子：
2.6
通讯作者：
Kroll, Jens
中科院分区：
文献类型：
--
作者：
Kroll, Jens
胆汁酸是源自肝脏中胆固醇的洗涤剂分子，对于肠道中脂质的代谢和吸收很重要。胆汁酸也是激活特定核受体和 G 蛋白偶联受体的类固醇激素。结合胆汁酸具有细胞保护作用和抗癌作用。胆汁酸合成和胆汁流量在衰老过程中显着减少。看家分子伴侣是应激反应蛋白，对于蛋白质、RNA 和 DNA 的折叠、维持和修复过程以及类固醇激素受体的结构和功能很重要。分子伴侣的表达水平与哺乳动物的寿命以及分化细胞的寿命相关。伴侣机制的功能在衰老过程中逐渐受损，这些管家机制的与年龄相关的渐进性损伤可能导致衰老的表型。本综述提供的证据表明，胆汁酸是化学伴侣，可改善一般伴侣防御，从而支持对哺乳动物寿命进化以及实现健康衰老可能具有重要意义的表观遗传机制。
Bile acids are detergent molecules derived from cholesterol in the liver that are important for the metabolism and absorption of lipids in the intestine. Bile acids are also steroid hormones activating specific nuclear receptors and G protein-coupled receptors. Conjugated bile acids are cytoprotective and anticarcinogenic. Bile acid synthesis and bile flow decreases markedly during aging. The housekeeping molecular chaperones are stress response proteins, important for the processes of folding, maintenance, and repair of proteins, RNA, and DNA, as well as for the structure and function of the steroid hormone receptors. The level of expression of the molecular chaperones correlates with mammalian longevity as well as with the life span of differentiated cells. The functions of the chaperone machinery are progressively impaired during aging, and the progressive age-related impairment of these housekeeping mechanisms probably contributes to the phenotype of aging. This review presents evidence that the bile acids are chemical chaperones, improving the general chaperone defense, and thus serve to support an epigenetic mechanism of possible significance for the evolution of mammalian longevity, as well as for the attainment of healthy aging.