Metformin slows down aging and extends life span of female SHR mice.
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 resemble 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. Here we show the chronic treatment of female outbred SHR mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but decreased the body weight after the age of 20 months, slowed down the age-related switch-off of estrous function, increased mean life span by 37.8%, mean life span of last 10% survivors by 20.8%, and maximum life span by 2.8 months (+10.3%) in comparison with control mice. On the other side, treatment with metformin failed influence blood estradiol concentration and spontaneous tumor incidence in female SHR mice. Thus, antidiabetic biguanide metformin dramatically extends life span, even without cancer prevention in this model.
Anisimov
Vladimir N
VN
N.N.Petrov Research Institute of Oncology, St. Petersburg, Russia. aging@mail.ru
Berstein
Lev M
LM
Egormin
Peter A
PA
Piskunova
Tatiana S
TS
Popovich
Irina G
IG
Zabezhinski
Mark A
MA
Tyndyk
Margarita L
ML
Yurova
Maria V
MV
Kovalenko
Irina G
IG
Poroshina
Tatiana E
TE
Semenchenko
Anna V
AV
D000375:Aging / Q000187:drug effects*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D030762:Estrous Cycle / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D006728:Hormones / Q000097:blood; D008136:Longevity / Q000187:drug effects*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000473:pathology; D016019:Survival Analysis
D006728:Hormones; D008687:Metformin