Metformin prevents murine ovarian aging

A number of studies have shown that metformin can delay aging process and extend healthy lifespan in animals. However, its role in female reproductive lifespan is unclear. This study was aimed to explore the potential anti-aging effect of metformin on the ovary and its possible mechanisms. Female C57BL/6 mice of 27-week old were divided into two groups, the control group (CON) and metformin-treated group (MET). CON mice were fed ad libitum, while MET mice were fed on chows supplied with 100mg/kg metformin for half a year. Ovarian reserve and function were assessed by ovarian follicle counts, estrous cycle and sex hormones levels. The expressions of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), and ovarian aging associated proteins P16, SIRT1, p-rpS6 and Bcl2 were examined. The MET mice exhibited increased level of serum E2 hormone and higher percentage of regular estrous cycles after 6 months' feeding, compared to the CON mice. The amount of primordial and primary follicles and the expression of SIRT1 were significantly increased, but the levels of P16, 8-OHdG, 4-HNE and p-rpS6 were decreased in the MET mice. These results indicate that metformin can delay ovarian aging process, probably by inducing the expression of SIRT1 and reducing the oxidative damage.