A woman's fertility tends to decline starting in her mid-thirties, making it more challenging to conceive during middle age. Recently, a team of scientists discovered a mechanism that appears to accelerate ovarian aging, and they found a way—at least in mice so far—to slow it down to enhance fertility later in life, according to New Atlas, citing the journal Nature Aging.
Not all organs age at the same rate, and unfortunately, the ovaries are among the fastest to experience this phenomenon, but scientists have not been entirely sure why. Starting around the age of 35, ovaries age more rapidly, leading to decreased egg quality and success in pregnancy. Many patients resort to in vitro fertilization, a method that can be costly and may introduce new risks.
In the new study, scientists at Zhengzhou University in China investigated the biological mechanisms that may underlie this decline. They analyzed gene expression patterns in young mice, approximately two months old, and middle-aged mice, around eight months old, in the ovaries and other organs.
Researchers found that in older mice, the expression of a gene called CD38 increased, especially in the ovaries. This was not entirely surprising, as the CD38 protein is a well-known biomarker of aging—it produces an enzyme that breaks down a protein called NAD+, which was later found to be at significantly lower levels in aged mice.
The NAD protein, along with its oxidized form NAD+, regulates cellular metabolism and DNA repair, and naturally decreases with age. Higher levels have been associated with longer lifespan and better health in aging, thus becoming a focus of recent anti-aging research with some promising results. It now seems that this common factor is also behind the age-related decline in fertility.
Cheng Ling Yang, a researcher in the new study, stated, "This depletion of [NAD+] represents a series of harmful effects, particularly impacting the quality of both somatic cells and oocytes, thereby exerting a profound effect on female fertility."
In follow-up experiments, the team deleted the CD38 gene in older mice, and indeed, the results showed an increase in the number of higher-quality oocytes. The researchers then began experiments to find out if a similar effect could be achieved without genetic engineering, making it a more viable fertility treatment.
To this end, the researchers turned to a molecule called 78c, which inhibits CD38, and administered it to eight-month-old lab mice. NAD+ levels in the ovaries increased, and the mice were able to conceive more successfully.
Clinical trials are currently underway to determine if enhancing NAD+ levels in women undergoing assisted reproductive treatments can improve success rates and reduce the risk of birth defects.
