Synopsis

Peak fertility occurs around age 25, begins declining after 30, and accelerates after 35. Women are born with a fixed number of oocytes forming the ovarian reserve, and both quantity and quality decline over time. The hallmarks of aging appear in ovaries even before measurable decline in ovarian reserve, suggesting these mechanisms could be targeted to preserve reproductive health.

NAD+ levels decline with age across various tissues, including the ovaries. In mice, reduced ovarian NAD+ associates with reproductive aging. As an essential molecule required in over 500 bodily reactions, NAD+ supports energy production through glycolysis and oxidative phosphorylation, along with longevity and cellular stress response pathways.

NAD+ enables critical functions including DNA repair, mitochondrial function, cell proliferation, and immune function through NAD+-dependent enzymes like sirtuins, CD38, and PARPs. These enzymes maintain cellular integrity and longevity while playing significant roles in ovarian aging.

Animal studies demonstrate that NAD+ precursors NMN and NR can improve ovarian aging. In aged mice, NMN enhanced oocyte quality by elevating SIRT2 levels, preventing spindle and chromosome defects that cause pregnancy loss. NMN also triggered positive responses in mitochondrial function, inflammation, ovarian atrophy, and hormone secretion.

For assisted reproductive technologies, NMN supplementation protected healthy embryo numbers and fertilization success in aged mice, even helping those with mitochondrial DNA mutations conceive. NR improved mature egg and early embryo quality by reducing oxidative stress and maintaining normal chromosome structure.