Hawcroft D M, Jones T W, Martin P A
Arch Gerontol Geriatr. 1982 May;1(1):55-74. doi: 10.1016/0167-4943(82)90006-1.
Liver microsomes were isolated from male mice of various defined ages, and their ability to metabolise ethylmorphine, p-nitroanisole, p-aminobenzoic acid and aniline was assessed as was their content of cytochrome P-450, cytochrome b-5 and protein, and their lipid composition. The rising capacity of the microsomes to metabolise these substrates in the first half of the lifespan was associated with a rise in the cytochrome P-450 and cytochrome b-5 content as well as an increase in the ratio of phosphatidylcholine to both phosphatidylethanolamine and sphingomyelin and, in early adult life, decreasing saturation of phospholipid fatty acids. The lipid changes would be expected to increase microsomal membrane fluidity. Declining mixed function oxidase activity in later life paralleled a decline in the ratio of phosphatidylcholine to phosphatidylethanolamine and sphingomyelin, and progressively reduced saturation of phospholipid fatty acids. Cytochrome content showed only a slight irregular decline with advancing age until the oldest animals were investigated, in which cytochrome b-5 was considerably reduced. Unfortunately, cytochrome P-450 was not measured in the oldest available group. Inducing the mixed function oxidase system with daily phenobarbitone injections for 4 days substantially increased enzyme activity in animals up to the middle of the age range tested. Older animals showed progressively reduced induction and none at all was seen in the oldest group. In contrast with the situation in non-induced mice, these changes were more closely associated with changes in cytochrome P-450 content than with alterations of lipid composition.
从不同特定年龄的雄性小鼠中分离出肝微粒体，评估其代谢乙基吗啡、对硝基苯甲醚、对氨基苯甲酸和苯胺的能力，以及其细胞色素P-450、细胞色素b-5和蛋白质的含量及其脂质组成。在寿命的前半段，微粒体代谢这些底物的能力不断增强，这与细胞色素P-450和细胞色素b-5含量的增加以及磷脂酰胆碱与磷脂酰乙醇胺和鞘磷脂的比例增加有关，并且在成年早期，磷脂脂肪酸的饱和度降低。脂质变化预计会增加微粒体膜的流动性。在生命后期，混合功能氧化酶活性下降与磷脂酰胆碱与磷脂酰乙醇胺和鞘磷脂的比例下降以及磷脂脂肪酸饱和度逐渐降低平行。直到研究最老的动物时，细胞色素含量才随着年龄的增长呈现出轻微的不规则下降，其中细胞色素b-5大幅降低。不幸的是，在最老的可用组中未测量细胞色素P-450。每天注射苯巴比妥4天诱导混合功能氧化酶系统，在测试年龄范围的中年之前的动物中，酶活性大幅增加。年龄较大的动物诱导作用逐渐降低，在最老的组中根本没有诱导作用。与未诱导小鼠的情况相反，这些变化与细胞色素P-450含量的变化比与脂质组成的改变更密切相关。
