A new study has shown that NMN significantly improves mitochondrial function and energy metabolism in the ovaries of aging mice, reduces ovarian inflammation, and reverses ovarian aging.



Background

Ovarian function gradually declines with age, leading to decreased fertility and various health issues. Nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for numerous cellular processes including energy metabolism, oxidative stress response, and inflammation, plays a pivotal role in maintaining ovarian health. Age-related decline in NAD+ levels is linked to a multitude of age-associated diseases. Nicotinamide mononucleotide (NMN), a precursor of NAD+, has shown promise in elevating intracellular NAD+ levels. This study aimed to investigate the potential of NMN in mitigating ovarian aging and provide novel therapeutic strategies for age-related infertility in women.


Research Methods and Procedures

Experimental Design:The research team selected aged mice as the study subjects and observed the inhibitory effects of NMN on ovarian aging through both short-term and long-term administration.

Administration Methods:Short-term administration: Used to assess the effects of NMN on ovarian NAD+ levels, ovary-to-body weight ratio, and ovarian atrophy.

Long-term administration: Further explored the sustained impact of NMN on ovarian aging.

Detection Indicators:These include ovarian NAD+ levels, ovary-to-body weight ratio, ovarian atrophy, serum hormone secretion, antioxidant factor levels, and pro-inflammatory factor expression.

Technical Approaches:A scanning electron microscope was used to observe changes in lipid droplets and mitochondria within ovarian granulosa cells. Transcriptome sequencing and validation experiments were conducted to reveal the mechanisms of NMN action.


Research Results

Short-term administration results:

Significantly increased ovarian NAD+ levels and ovarian-to-body weight ratio in aged mice.

Inhibited ovarian atrophy.

Promoted the quality of ovulated oocytes.

NMN treatment significantly increased the quantity and quality of ovulated oocytes in aged mice.


Long-term administration results:

Improved serum hormone secretion and antioxidant levels in aged mice.

Decreased expression of pro-inflammatory factors.

Significantly increased the number of ovarian follicles in aged mice.


Results:

NMN significantly altered the density, morphology, and distribution of lipid droplets and mitochondria in granulosa cells, revealing potential targets and mechanisms.

The beneficial effects of NMN on aging ovaries were achieved by enhancing mitochondrial function, improving energy metabolism, and reducing inflammation levels.

NMN markedly regulated gene expression in aging ovaries, particularly genes associated with energy metabolism and inflammatory responses.


Research Significance

This study provides valuable insights into reproductive medicine, contributing to the development of more effective therapeutic strategies to address fertility issues associated with ovarian aging.

As a promising intervention, the study of NMN’s anti-aging mechanisms offers new perspectives for treating age-related fertility decline in women, particularly those of advanced maternal age.

Additionally, the findings highlight the positive impact of NMN supplementation on aging ovaries, demonstrating its ability to regulate a wide range of ovarian genes associated with aging. These results not only deepen our understanding of ovarian aging but also pave the way for future research into innovative approaches for improving reproductive health.