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

Aging (Albany NY). 2010 Dec;2(12):945-58. doi: 10.18632/aging.100245.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / physiology*
  • Animals
  • Blood Glucose / metabolism
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Cholesterol / blood
  • Chromosome Aberrations / chemically induced
  • Drinking / drug effects
  • Eating / drug effects
  • Estrus / drug effects
  • Female
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / toxicity
  • Insulin / blood
  • Longevity / drug effects*
  • Male
  • Metformin / pharmacology*
  • Metformin / toxicity
  • Mice
  • Mice, 129 Strain
  • Neoplasms / etiology
  • Neoplasms / pathology
  • Neoplasms / prevention & control*
  • Sex Factors
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Triglycerides
  • Metformin
  • Cholesterol