Abstract
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.
Highlights
To test strain and gender factors in present study we evaluated effects of metformin on some parameters of aging, life span and spontaneous tumorigenesis in inbred male and female 129/Sv mice
Male 129/Sv mice were heavier than females over the life span both in the control and treated with metformin groups (Fig. 1)
The body weight of mice in both control and metformin-treated groups increased with age, exceeding at 18 months the body weight of 3month-old animals by 27.7% in the control female group, and by 30.5 % in the female group treated with metformin
Summary
Microvascular damage [5]. It is important to stress that hyperinsulinemia is an significant factor in aging and in the development of cancer [5,13,14,15,16,17,18]. To test strain and gender factors in present study we evaluated effects of metformin on some parameters of aging, life span and spontaneous tumorigenesis in inbred male and female 129/Sv mice. The amount of food daily consumed by male mice was higher than in females throughout the whole period of observation (Fig. 2) It was approximately similar in the controls and in metformin-treated male and female groups until the age of 1 year. At the age of 15 to 21 months the food consumption was slightly but significantly (p
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