Hafnia Unit of Biogerontology, Frederiksberg, Denmark.
Rejuvenation Res. 2012 Apr;15(2):210-2. doi: 10.1089/rej.2011.1286.
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.
胆汁酸是肝脏胆固醇衍生的去污剂分子，对于肠道中脂质的代谢和吸收非常重要。胆汁酸也是激活特定核受体和 G 蛋白偶联受体的甾体激素。结合胆汁酸具有细胞保护和抗癌作用。胆汁酸合成和胆汁流量在衰老过程中显著下降。管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甾体激素受体的结构和功能非常重要。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。随着年龄的增长，伴侣蛋白机器的功能逐渐受损，这些管家机制的进行性年龄相关性损伤可能导致衰老表型。本综述提供的证据表明，胆汁酸是化学伴侣，可改善一般伴侣蛋白防御，从而有助于支持可能对哺乳动物长寿进化以及健康衰老具有重要意义的表观遗传机制。
