Metformin prevents murine ovarian aging.

Xian Qin,Dingfu Du,Tong Wu,Shixuan Wang,Qian Chen,Meng Wu,Jinjin Zhang,Jingyi Wen,Yan Jin

doi:10.18632/aging.102016

Xian Qin, Dingfu Du + Show 7 more

Open Access

https://doi.org/10.18632/aging.102016

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Abstract

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.

Highlights

The ovary, regarded as an aging pacemaker, appears to age at the earliest stage during a woman’s lifespan [1]
One study suggested that the health lifespan of C57/BL mice could be prolonged by feeding with 100mg/kg metformin [11]
Mice of 28-week old were selected in this study, 100mg/kg metformin was given for half a year to explore whether the intervention of recommended metformin dosage could delay the ovarian aging process and extend reproductive span

Summary

Introduction

The ovary, regarded as an aging pacemaker, appears to age at the earliest stage during a woman’s lifespan [1]. Ovarian aging refers to the decline of female ovarian functions with age, accompanied by the deterioration in the quantity and quality of ovarian follicles, and ends with menopause. This aging process is complicated and affected by a number of factors, including lifestyle, medical, genetic, autoimmune, environmental, and idiopathic ones. It is often highly associated with other disorders in women. With the delay of women's child-bearing age, ovarian aginginduced reproductive problems have become a big issue to the mankind. A marked progress has been made in the exploration of anti-ovarian aging agents or approaches, such as calorie restriction mimetics, antioxidants, autophagy inducers, epigenetic drugs, immunomodulator etc., over the past years, none of these have become clinically effective or useful

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