Article

Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.

Department of Carcinogenesis and Oncogerontology, N.N.Petrov Research Institute of Oncology, Pesochny-2, St Petersburg 197758, Russian Federation.
Experimental Gerontology (impact factor: 3.74). 40(8-9):685-93. DOI:10.1016/j.exger.2005.07.007 pp.685-93
Source: PubMed

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. 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 1 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.

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Keywords

blood glucose
 
calorie restriction
 
chronic treatment
 
control mice
 
corresponding genes
 
decreasing IGF-1 levels
 
drinking water
 
female transgenic HER-2/neu mice
 
food consumption
 
insulin/IGF-1 signaling pathway
 
Insulin/insulin-like growth factor 1
 
last 10% survivors
 
life span
 
maximum life span
 
mean life span
 
mimetic effects
 
perspective direction
 
pharmacological modulators
 
respective Gompertz's parameter
 
triglycerides level