The aging process of the ovaries, similar to the thymus, is of particular interest due to its rapid degeneration with age. This raises the question of whether studying organs that age more quickly can provide insight into the general aging process. Researchers explore NAD+ metabolism in the ovaries compared to other tissues, noting that the enzyme CD38, which depletes NAD+, is more active earlier in life. Maintaining NAD+ levels has been shown to slow ovarian aging, including through the knockout of CD38.
The decline in ovarian function occurs earlier than in most other female organs, posing implications for delayed childbearing, which is a common trend globally. Oocyte quality and ovarian reserve decrease significantly in middle age. To better understand the molecular mechanisms behind ovarian senescence, researchers studied the transcriptome changes in the ovaries of middle-aged mice. They discovered that aging-related pathways were misregulated in the ovaries but not in other organs, with increased expression of aging markers and inflammation-related factors. Ovarian aging appears to occur earlier than in most other organs, with noticeable changes in gene expression as early as 6-12 months.
Notably, this study found that inflammation-related genes and the NAD+ metabolizing enzyme CD38 were rapidly activated in the middle-aged ovary, while key enzymes for NAD+ generation and metabolism remained unchanged. This activation of CD38 and inflammation-related transcripts was not observed in other organs. Previous studies have shown an increase in CD38 expression in aged mice, highlighting its role in ovarian senescence. Maintaining NAD+ levels through supplementation with NAD+ precursors or deletion of CD38 has been linked to delayed ovarian aging and improved ovarian function. Specifically, mice without CD38 showed increased ovarian follicle reserve, higher levels of serum anti-Mullerian hormone, and decreased cell DNA damage and apoptosis.
