Are sirtuins markers of ovarian aging?

Abstract

Sirtuins, a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases that play diverse roles in regulating metabolism, cell proliferation, and genome stability, have been implicated in mammalian aging and age-related diseases, including cancers, metabolic disorders, and neurodegenerative diseases. Ovarian aging is thought to be characterized by a gradual decrease in both the number of follicles and the quality of oocytes. Ovarian reserve is indicated by the number of primordial follicles. In this study, ovarian reserve was assessed in mice of different ages and mice subjected to caloric restriction (CR) and chemotherapy (2 commonly used models for ovarian aging research) by counting primordial follicles and determining the expression levels of SIRT1, SIRT3, and SIRT6 to explore the relationship between ovarian function and sirtuin expression. A gradual decline in the number of follicles (especially primordial follicles) was observed in aging mice and mice subjected to chemotherapy. Histological analysis showed that CR mice displayed a significantly greater number of primordial follicles and less atretic follicles. Western blot analysis indicated that expression levels of SIRT1, SIRT3, and SIRT6 were significantly decreased in the ovaries of aged mice and mice treated with chemotherapy, but increased in CR mice. SIRT1, SIRT3, and SIRT6 all showed a significantly positive correlation with the numbers of primordial follicles (r2=0.6399, P<0.0001; r2=0.5445, P<0.001; and r2=0.4956, P<0.0001, respectively). These results indicate that SIRT1, SIRT3 and SIRT6 are closely related to ovarian reserve, and suggest that these sirtuins may be markers of ovarian aging.