Longevity & Aging

CD38 in Macrophages Drives Uterine Aging by Depleting NAD+

Researchers identified NAD+ depletion as a hallmark of endometrial aging in mice, driven primarily by CD38-expressing macrophages infiltrating the uterus. Using metabolomics, single-cell RNA sequencing, and genetic mouse models, they showed that myeloid-derived CD38 consumes NAD+ in the uterine microenvironment, promoting stromal cell senescence and impairing implantation. Supplementing aged mice with NAD+ precursors alleviated senescence markers, improved endometrial architecture, and restored embryo implantation rates. These findings establish a macrophage–NAD+ axis as a central driver of reproductive aging and identify CD38 as a potential therapeutic target for improving fertility in older women.