title: Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice.
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.
authors.affiliation: N.N.Petrov Research Institute of Oncology, Pesochny-2, St.Petersburg 197758, Russia. aging@mail.ru
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Anisimov
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Piskunova
authors.forename: Irina G
authors.initials: IG
authors.lastname: Popovich
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zabezhinski
authors.forename: Margarita L
authors.initials: ML
authors.lastname: Tyndyk
authors.forename: Peter A
authors.initials: PA
authors.lastname: Egormin
authors.forename: Maria V
authors.initials: MV
authors.lastname: Yurova
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Rosenfeld
authors.forename: Anna V
authors.initials: AV
authors.lastname: Semenchenko
authors.forename: Irina G
authors.initials: IG
authors.lastname: Kovalenko
authors.forename: Tatiana E
authors.initials: TE
authors.lastname: Poroshina
authors.forename: Lev M
authors.initials: LM
authors.lastname: Berstein
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002869:Chromosome Aberrations / Q000139:chemically induced; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004971:Estrus / Q000187:drug effects; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000633:toxicity; D007328:Insulin / Q000097:blood; D008136:Longevity / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D057507:Mice, 129 Strain; D009369:Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014280:Triglycerides; D008687:Metformin; D002784:Cholesterol