Intermittent fasting reverses the declining quality of aged oocytes

Decreased oocyte quality and compromised embryo development are particularly prevalent in older females, but the aging-related cellular processes and effective ameliorative approaches have not been fully characterized. Intermittent fasting (IF) can help improve health and extend lifespan; nevertheless, how it regulates reproductive aging and its mechanisms remain unclear. We used naturally aged mice to investigate the role of IF in repro-duction and found that just one month of every-other-day fasting was sufficient to improve oocyte quality. IF not only increased antral follicle numbers and ovulation but also enhanced oocyte meiotic competence and em-bryonic development by improving both nuclear and cytoplasmic maturation in maternally aged oocytes. The beneficial effects of IF manifested as alleviation of spindle structure abnormalities and chromosome segregation errors and maintenance of the correct cytoplasmic organelle reorganization. Moreover, single-cell transcriptome analysis showed that the positive impact of IF on aged oocytes was mediated by restoration of the nicotinamide adenine dinucleotide (NAD+)/Sirt1-mediated antioxidant defense system, which eliminated excessive accumu-lated ROS to suppress DNA damage and apoptosis. Collectively, these findings suggest that IF is a feasible approach to protect oocytes against advanced maternal age-related oxidation damage and to improve the reproductive outcomes of aged females.