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Published on: February 12, 2018
Metformin slows down aging and extends life span of female SHR mice
Vladimir N Anisimov1, Lev M Berstein, Peter A Egormin
1N.N.Petrov Research Institute of Oncology, St. Petersburg, Russia. aging@mail.ru
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 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.
Insights
Metformin, an antidiabetic drug, significantly extended the lifespan of female mice by 37.8%. This longevity effect was observed despite no impact on tumor incidence, suggesting a complex role in aging.
Area of Science:
- Gerontology and Longevity Research
- Pharmacology and Drug Discovery
- Metabolic Disease and Aging
Background:
- Hyperglycemia and hyperinsulinemia are implicated in mammalian aging and cancer development.
- Calorie restriction's life-prolonging effects may be mediated by reduced Insulin-like Growth Factor 1 (IGF-1) levels.
- Pharmacological targeting of the insulin/IGF-1 signaling pathway presents a promising strategy for longevity regulation.
Purpose of the Study:
- To investigate the effects of the antidiabetic biguanide metformin on the lifespan and aging process in female mice.
- To explore metformin's potential as a pharmacological modulator of the insulin/IGF-1 signaling pathway for longevity.
Main Methods:
- Chronic administration of metformin (100 mg/kg) in drinking water to female outbred SHR mice.
- Monitoring of food consumption, body weight, estrous function, and survival parameters (mean, 10% survivor, and maximum lifespan).
- Assessment of blood estradiol concentration and spontaneous tumor incidence in treated and control groups.
Main Results:
- Metformin treatment led to a significant increase in mean lifespan (+37.8%), mean lifespan of the last 10% survivors (+20.8%), and maximum lifespan (+10.3%).
- Metformin decreased body weight after 20 months of age and slowed the age-related decline of estrous function.
- No significant influence of metformin on blood estradiol concentration or spontaneous tumor incidence was observed.
Conclusions:
- The antidiabetic biguanide metformin dramatically extends lifespan in female SHR mice.
- Metformin's life-extending effects are achieved independently of changes in estradiol levels or tumor prevention.
- Metformin represents a promising pharmacological intervention for modulating longevity, warranting further investigation.
