NMN Can Restore Ovarian Reserve in Aged Mice by Upregulating NAD+/SIRT1/PGC-1α Signaling Pathway and TOMM20 Expression, and Improve in Vitro Development of Aging Oocytes.

Female reproductive aging is linked to declining nicotinamide adenine dinucleotide (NAD+) levels and mitochondrial dysfunction. While nicotinamide mononucleotide (NMN) supplementation can counteract this, its mechanisms remain unclear. This study investigated NMN’s effects in aged female mice administered 200, 500, or 1000 mg/kg/day NMN for 10 days, compared to aged and young controls. An optimal dose of 500 mg/kg/day was identified for restoring ovarian follicle reserve. This treatment significantly increased ovarian NAD+ and ATP, reduced oocyte oxidative stress (ROS) and apoptosis, and rejuvenated mitochondrial function. Mechanistically, NMN activated the NAD+/SIRT1/PGC-1α signaling pathway and upregulated the mitochondrial biogenesis protein TOMM20. In vitro, supplementing culture medium with 1 µM NMN optimally enhanced the developmental potential of aged oocytes. Both in vivo and in vitro interventions showed dose-dependent efficacy. We conclude that NMN mitigates ovarian aging by enhancing mitochondrial function via the NAD+/SIRT1/PGC-1α-TOMM20 axis.