Internal medicine

Enzyme

Cofactor

Nicotinamide adenine dinucleotide

Population

Biology

Endocrinology

Andrology

Oocyte

Embryo

Nicotinamide mononucleotide

Fertility preservation

Fertility

Fecundity

NAD+ kinase

Cell biology

Genetics

Biochemistry

Reproduction

Medicine

Environmental health

Cell Reports

Reproductive aging in female mammals is an irreversible process associated with declining oocyte quality, which is the rate-limiting factor to fertility. Here, we show that this loss of oocyte quality with age accompanies declining levels of the prominent metabolic cofactor nicotinamide adenine dinucleotide (NAD+). Treatment with the NAD+ metabolic precursor nicotinamide mononucleotide (NMN) rejuvenates oocyte quality in aged animals, leading to restoration in fertility, and this can be recapitulated by transgenic overexpression of the NAD+-dependent deacylase SIRT2, though deletion of this enzyme does not impair oocyte quality. These benefits of NMN extend to the developing embryo, where supplementation reverses the adverse effect of maternal age on developmental milestones. These findings suggest that late-life restoration of NAD+ levels represents an opportunity to rescue female reproductive function in mammals.

NAD+ Repletion Rescues Female Fertility during Reproductive Aging