News | Study Links Declining NAD+ Levels to Ovarian Aging and Fertility
As women age, fertility generally begins to decline in their late 30s and ends at menopause. A small molecule called nicotinamide adenine dinucleotide (NAD+) is known to play a key role in this process. Scientists at the Buck Institute recently identified how declining NAD+ levels affect ovarian function and found a potential way to extend reproductive lifespan.
Dr. Eric Verdin, president and CEO of the Buck Institute and senior author of the study, said, "Studying ovarian biology and reproductive aging is not only about improving fertility, but also about women's overall health. By understanding the processes associated with menopause and declining fertility, we hope to explore how these changes relate to women's overall lifespan and healthspan."
The Link Between NAD+ and Ovarian Function
NAD+ is an essential molecule found in every cell of the body, and its levels gradually decline with age. The study found that this also occurs in the ovaries, where reduced NAD+ leads to fewer eggs and poorer egg quality, affecting female fertility.
Co-first author Dr. Rosalba Perrone explained, "We already knew that NAD+ is important for supporting ovarian function, but we did not understand why it declines with age or what drives that decline."
The Role of the Key Enzyme CD38
To investigate the molecular mechanism behind falling NAD+ levels, the team focused on an enzyme called CD38, one of the primary enzymes that breaks down NAD+. CD38 expression rises with age, accelerating NAD+ degradation and aging. Its specific role in female reproductive function, however, had not previously been clear.
The researchers found for the first time that CD38 is mainly present in ovarian immune cells within specific structures outside the follicles. As ovarian CD38 expression increased with age, NAD+ levels fell correspondingly, demonstrating CD38's key role in this decline.
Potential for Future Treatment
The study further showed that mice lacking CD38 had more primordial follicles, which eventually mature and release eggs. Women are born with a limited number of primordial follicles, which determines ovarian lifespan and fertility. The findings suggest that CD38 regulates ovarian function and fertility and that targeting CD38 may help extend reproductive lifespan.
Dr. Perrone said, "CD38 is clearly a potential drug target. Small-molecule drugs and antibodies already exist that can recognize CD38 and prevent it from degrading NAD+. Regulating CD38 activity to improve fertility, particularly when pregnancy is desired, has considerable potential."
Although the study focused mainly on the effects of CD38 on NAD+ metabolism and fertility, Dr. Perrone emphasized that its significance extends beyond reproduction. "Menopause is associated not only with the loss of reproductive capacity but also with women's overall lifespan and healthspan. Understanding how to keep reproductive organs functioning well is therefore essential to studying aging in women."
News | Study Links Declining NAD+ Levels to Ovarian Aging and Fertility
News | Study Links Declining NAD+ Levels to Ovarian Aging and Fertility
As women age, fertility generally begins to decline in their late 30s and ends at menopause. A small molecule called nicotinamide adenine dinucleotide (NAD+) is known to play a key role in this process. Scientists at the Buck Institute recently identified how declining NAD+ levels affect ovarian function and found a potential way to extend reproductive lifespan.
Dr. Eric Verdin, president and CEO of the Buck Institute and senior author of the study, said, "Studying ovarian biology and reproductive aging is not only about improving fertility, but also about women's overall health. By understanding the processes associated with menopause and declining fertility, we hope to explore how these changes relate to women's overall lifespan and healthspan."
The Link Between NAD+ and Ovarian Function
NAD+ is an essential molecule found in every cell of the body, and its levels gradually decline with age. The study found that this also occurs in the ovaries, where reduced NAD+ leads to fewer eggs and poorer egg quality, affecting female fertility.
Co-first author Dr. Rosalba Perrone explained, "We already knew that NAD+ is important for supporting ovarian function, but we did not understand why it declines with age or what drives that decline."
The Role of the Key Enzyme CD38
To investigate the molecular mechanism behind falling NAD+ levels, the team focused on an enzyme called CD38, one of the primary enzymes that breaks down NAD+. CD38 expression rises with age, accelerating NAD+ degradation and aging. Its specific role in female reproductive function, however, had not previously been clear.
The researchers found for the first time that CD38 is mainly present in ovarian immune cells within specific structures outside the follicles. As ovarian CD38 expression increased with age, NAD+ levels fell correspondingly, demonstrating CD38's key role in this decline.
Potential for Future Treatment
The study further showed that mice lacking CD38 had more primordial follicles, which eventually mature and release eggs. Women are born with a limited number of primordial follicles, which determines ovarian lifespan and fertility. The findings suggest that CD38 regulates ovarian function and fertility and that targeting CD38 may help extend reproductive lifespan.
Dr. Perrone said, "CD38 is clearly a potential drug target. Small-molecule drugs and antibodies already exist that can recognize CD38 and prevent it from degrading NAD+. Regulating CD38 activity to improve fertility, particularly when pregnancy is desired, has considerable potential."
Although the study focused mainly on the effects of CD38 on NAD+ metabolism and fertility, Dr. Perrone emphasized that its significance extends beyond reproduction. "Menopause is associated not only with the loss of reproductive capacity but also with women's overall lifespan and healthspan. Understanding how to keep reproductive organs functioning well is therefore essential to studying aging in women."
Source:
Collected online