This study found that declining NAD+ levels are associated with age-related decline in oocyte quality and female fertility in mice. Treatment with NMN, an NAD+ precursor, restored oocyte quality, improved embryo development, and increased live birth rates in aged mice. Similar effects were seen in aged Sirt2Tg/+ mice, though Sirt2 deletion alone did not impair oocyte quality in younger animals, suggesting a potential role for this enzyme.

Several authors (L.E.W., H.A.H., and D.A.S.) have financial interests in Jumpstart Fertility Inc., a company which has licensed a patent based on this work. Other authors hold shares or have consulted for this company. D.A.S. also has financial interests in various other companies related to aging and health. Although the authors acknowledge these conflicts, their significant involvement raises concerns about potential bias in the study design, interpretation, and reporting of results. K.S. was an employee of Jumpstart Fertility, raising concerns about bias in performing experiments and analyzing results. The funding sources included research contracts from Jumpstart Fertility. While these do not negate the findings, they necessitate a careful review of the study's methodology and interpretation of the results.

This study provides compelling evidence that NAD+ repletion can rejuvenate oocyte quality and improve fertility in aged mice. The use of multiple approaches, including pharmacological intervention, genetic manipulation, and in vitro embryo studies, strengthens the findings. The positive impact of NMN on developmental milestones in embryos is particularly noteworthy. However, the limitations regarding the generalizability to humans, the incomplete mechanistic understanding of SIRT2's role, and the significant financial conflicts of interest warrant caution in interpreting the results and necessitate further investigation.