Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice

被引:104
作者
Anisimov, Vladimir N. [1 ]
Piskunova, Tatiana S. [1 ]
Popovich, Irina G. [1 ]
Zabezhinski, Mark A. [1 ]
Tyndyk, Margarita L. [1 ]
Egormin, Peter A. [1 ]
Yurova, Maria N. [1 ]
Rosenfeld, Svetlana V. [1 ]
Semenchenko, Anna V. [1 ]
Kovalenko, Irina G. [1 ]
Poroshina, Tatiana E. [1 ]
Berstein, Lev M. [1 ]
机构
[1] NN Petrov Oncol Res Inst, St Petersburg 197758, Russia
来源
AGING-US | 2010年 / 2卷 / 12期
基金
俄罗斯基础研究基金会;
关键词
metformin; biomarkers of aging; life extension; carcinogenesis; mice; TRANSGENIC MOUSE MODEL; CALORIC RESTRICTION; CANCER; INSULIN; KINASE; GROWTH; PHENFORMIN; TUMORS; DIPHENYLHYDANTOIN; SENESCENCE;
D O I
10.18632/aging.100245
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 mimetic 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. The chronic treatment of inbred 129/Sv mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but failed to influence the dynamics of body weight, decreased by 13.4% the mean life span of male mice and slightly increased the mean life span of female mice (by 4.4%). The treatment with metformin failed influence spontaneous tumor incidence in male 129/Sv mice, decreased by 3.5 times the incidence of malignant neoplasms in female mice while somewhat stimulated formation of benign vascular tumors in the latter.
引用
收藏
页码:945 / 958
页数:14
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