Metformin slows down aging and extends life span of female SHR mice
Metformin slows down aging and extends life span of female SHR mice
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DOI：
10.4161/cc.7.17.6625
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发表时间：
2008-09-01
期刊：
影响因子：
4.3
通讯作者：
Semenchenko, Anna V.
中科院分区：
文献类型：
--
作者：
Anisimov, Vladimir N.;Berstein, Lev M.;Semenchenko, Anna V.
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展的重要因素。卡路里限制的延长寿命效果可能是由于IGF-1水平的降低。寻找胰岛素/IGF-1信号通路的药理学调节剂（类似于延长寿命的突变或卡路里限制的作用）可能是长寿调节的一个前景方向。抗糖尿病的双胍类药物是其中最有前途的。本研究显示，雌性近交系SHR小鼠经二甲双胍（100 mg/kg饮用水）慢性治疗后，在20月龄后，食量略有改变，但体重下降，与年龄相关的发情功能关闭减慢，平均寿命比对照小鼠增加37.8%，最后10%幸存者的平均寿命增加20.8%，最大寿命增加2.8个月（+ 10.3%）。另一方面，二甲双胍治疗失败影响雌性SHR小鼠血雌二醇浓度和自发性肿瘤发生率。因此，抗糖尿病的双胍类二甲双胍即使在没有癌症预防的情况下也能显著延长寿命。
Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. 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 resemble effects of life span extending mutations or calorie restriction) could be a perspective direction in regulation of longevity. Antidiabetic biguanides are most promising among them. Here we show the chronic treatment of female outbred SHR mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but decreased the body weight after the age of 20 months, slowed down the age-related switch-off of estrous function, increased mean life span by 37.8%, mean life span of last 10% survivors by 20.8%, and maximum life span by 2.8 months (+ 10.3%) in comparison with control mice. On the other side, treatment with metformin failed influence blood estradiol concentration and spontaneous tumor incidence in female SHR mice. Thus, antidiabetic biguanide metformin dramatically extends life span, even without cancer prevention in this model.