Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice
Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice
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DOI：
10.1016/j.exger.2005.07.007
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发表时间：
2005-08-01
影响因子：
3.9
通讯作者：
Franceschi, C
中科院分区：
文献类型：
--
作者：
Anisimov, VN;Berstein, LM;Franceschi, C
对哺乳动物的研究表明，高血糖和高胰岛素血症是衰老和癌症发生的重要因素。与长寿相关的胰岛素/胰岛素样生长因子1（IGF - 1）信号分子包括秀丽隐杆线虫中的DAF - 2和果蝇及哺乳动物中的InR及其同源物，相应基因失活后，线虫、果蝇和小鼠的寿命会延长。热量限制的延寿作用可能是由于IGF - 1水平降低。寻找胰岛素/IGF - 1信号通路的药理调节剂（模拟延寿突变或热量限制的效应）可能是调控长寿的一个有前景的方向。用二甲双胍（饮用水中100mg/kg）对雌性转基因HER - 2/neu小鼠进行长期治疗，略微降低了食物摄入量，但未能降低体重或体温，减缓了与年龄相关的血糖和甘油三酯水平的升高以及与年龄相关的发情功能关闭，与对照小鼠相比，平均寿命延长了8%（p < 0.05），最后10%存活者的平均寿命延长了13.1%，最大寿命延长了1个月。以相应的冈珀茨参数估计值表示的人口老龄化率降低了2.26倍。二甲双胍治疗显著降低了小鼠乳腺腺癌的发病率和肿瘤大小，并增加了肿瘤的平均潜伏期。（c）2005爱思唯尔公司。保留所有权利。
Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include DAF-2 and InR and their homologues in mammals, and inactivation of the corresponding genes is followed by increased life span in nematodes, fruit flies and mice. It is possible that the life-prolonging effects of calorie restriction are due to decreasing IGF-1 levels. A search of pharmacological modulators of insulin/IGF-1 signaling pathway (which mimetic effects of life span extending mutations or calorie restriction) could be a perspective direction in regulation of longevity. The chronic treatment of female transgenic HER-2/neu mice with metformin (100 mg/kg in drinking water) slightly decreased the food consumption but failed in reducing the body weight or temperature, slowed down the age-related rise in blood glucose and triglycerides level, as well as the age-related switch-off of estrous function, prolonged the mean life span by 8% (p < 0.05), the mean life span of last 10% survivors by 13.1%, and the maximum life span by I month in comparison with control mice. The demographic aging rate represented by the estimate of respective Gompertz's parameter was decreased 2.26 times. The metformin-treatment significantly decreased the incidence and size of mammary adenocarcinomas in mice and increased the mean latency of the tumors. (c) 2005 Elsevier Inc. All rights reserved.