Women’s fertility tends to decline starting in their mid-30s, which can make it harder to have kids in middle age. Now scientists have identified a mechanism that seems to accelerate aging of the ovaries – and found a way, in mice at least, to slow it down to boost fertility later in life.
Our organs don’t all age at the same rate, and the ovaries are unfortunately one of the fastest to do so, but scientists aren’t exactly sure why. Beginning from about the age of 35, the ovaries age faster, leading to reduced egg quality and success in conceiving. Many patients turn to IVF, but that process can be expensive and brings new risks.
For the new study, scientists at Zhengzhou University in China investigated the biological mechanisms that might be behind this decline. They analyzed patterns of gene expression in young mice about two months of age, and middle-aged mice around eight months old, in the ovaries and other organs.
They found that in the older mice, expression of a gene called CD38 increased, and especially so in the ovaries. This wasn’t entirely surprising – CD38 is a known biomarker of aging, since it produces an enzyme that degrades a protein called NAD+, which was subsequently found at much lower levels in the aged mice.
NAD, and its oxidized form NAD+, regulate cell metabolism and DNA repair, and naturally decline with age. Higher levels have been correlated with longer lifespans and better health with age, so it’s become the focus of recent anti-aging research, with some promising results. Now it seems this common cause is also behind age-related declines in fertility.
“This depletion [of NAD+] sets forth a cascade of detrimental effects, particularly impacting the quality of both somatic cells and oocytes, thereby exerting a profound influence on female fertility,” said Qingling Yang, an author of the study.
In follow-up experiments, the team deleted the CD38 gene in older mice – and sure enough, they had more eggs of higher quality, and produced more pups per litter. Next, the researchers investigated if a similar effect could be achieved without genetic engineering, to make it a more feasible fertility treatment.
The team turned to a molecule called 78c, which inhibits CD38, and gave it to naturally aged eight-month-old mice. Sure enough, levels of NAD+ increased in their ovaries, and the mice were able to have more pups.
As promising as the research is, there’s always the caveat that it was conducted in mice, so the results might not necessarily translate to humans. On the plus side, though, clinical trials are already underway to investigate whether boosting NAD+ levels in women undergoing assisted reproductive treatments can improve the success rates and reduce the risk of birth defects.
The research was published in the journal Nature Aging.
Source: PNAS