NADase CD38 is a key determinant of ovarian lifespan

The ovary ages earlier than most other tissues in women, yet the underlying biological mechanisms and strategies to delay ovarian aging remain enigmatic. In this study, a comprehensive analysis of transcriptomic landscapes across different organs in young and middle-aged mice unveiled early expression of age-associated genes in ovaries. This analysis identified heightened NADase CD38 expression and reduced NAD+ levels in middle-aged mice ovaries. Bulk and single-cell RNA sequencing demonstrated that CD38 deletion counteracted ovarian aging, preserving fertility and maintaining follicle reserve in aged mice by addressing age-related gene expression changes and intercellular communication disruptions. In our research, we conducted a comparative transcriptomic analysis of various organs, including the heart, kidney, brain, lung, liver, and muscle (n=3-5), using RNA-Seq from young and middle-aged mice at 2 and 8 months of age, respectively. Additionally, we performed single-cell RNA-Seq on ovaries from young (2 months), middle-aged (8 months), and old (12 months) WT and old CD38-/- mice. To delve deeper into the effects of CD38 on MII quality, we also collected oocyte transcriptomes from young (2 months) and old (12 months) WT and old CD38-/- mice using smart-Seq.