NMN and NR Alleviate Ovarian Aging in Rats

A recent study investigated the effects of NMN and NR on ovary health and function in middle-aged rats.

“This study reveals that NMN alone or NR alone can rebalance mitochondrial dynamics by decreasing excessive fission in middle-aged rat ovaries, thus alleviating mitochondrial stress and correcting aging-induced folliculogenesis abnormalities.”

Key Points:

  • NMN and NR improved ovarian function and follicle quality in middle-aged rats
  • NMN and NR increased SIRT1 expression
  • Effects were mediated through the rebalancing of mitochondrial dynamics
  • NMN and NR were equally effective

NMN And NR Rescued Mitochondrial Dynamics And Follicle Quality In Rats:

Young and middle-aged female rats were divided into four groups to assess the effects of NMN or NR administration on metrics of ovarian aging:

  • Young (5 months old)
  • Middle-aged (control, 12 months old)
  • Middle-aged + NMN (500 mg/kg, injection)
  • Middle-aged + NR (200 mg/kg, oral)

NMN and NR were administered for 17 days.

Hormone levels, ovarian weight, follicle counts, and the expression of mitochondrial dynamics-related genes and proteins were assessed.

Improved Ovarian Function and Follicle Quality

Ovarian index, a measure of ovarian health, was higher in rats treated with NMN and NR (0.143 and 0.142) compared to the middle-aged control group (0.134).

The number of corpus luteum, temporary structures in the ovary that form after an egg is released, were also higher in the NMN (9) and NR (7) groups compared to the control (5).

Older rats had higher FSH levels, a sign of lower ovary function. However, rats treated with NMN and NR had lower FSH levels, closer to the levels observed in young rats.

The LH/FSH ratio, an indicator of healthy ovulation, improved in the NMN (0.95) and NR (0.91) groups compared to the control (0.66).

NMN and NR Protected Follicle Integrity

NMN and NR prevented the degradation of follicles (atresia) that was observed in the untreated rats.

“NMN alone or NR alone improved follicle quality by reducing atresia.”

The number of healthy follicles was 31.25% and 25% higher in the NMN and NR groups compared to the control.

Additionally, NMN and NR reduced the number of dying follicles by 50% and 40% respectively.

This graph shows the number of healthy (antral) and damaged (atretic) follicles in rat ovaries across different treatment groups.

  • The Young group (left) had the highest number of healthy follicles (35, black bars) and the fewest damaged follicles (8, gray bars).
  • The middle-aged Control group had fewer healthy follicles (16, black bars) and more damaged follicles (10, gray bars) compared to the young rats.
  • Treatment with NMN or NR in middle-aged rats increased healthy follicles to 21 and 20, respectively, while reducing damaged follicles to 5 and 6, respectively

Rebalanced of Mitochondrial Dynamics

Mitochondrial dynamics, a balance between fusion (indicating health) and fission (indicating decreased function), were disrupted in the ovaries of middle-aged rats.

NMN and NR treatment restored this balance by increasing the expression of fusion-related genes and proteins while decreasing those related to fission.

NMN and NR also increased the levels of SIRT1, a protein important for longevity, which was suppressed in the middle-aged control group.

Conclusion

NMN and NR slowed ovarian aging in rats by rebalancing mitochondrial dynamics mediated through SIRT1 activation.

The NMN and NR treatments improved hormonal balance, increased healthy follicles, protected them against deterioration, and increased follicle protective structures.

“The administration of a NAD+ precursor (NMN or NR) restores LH/FSH balance and mitochondrial dynamics, increases SIRT1 activity and alleviates folliculogenesis problems in middle-aged rats.”