Long-term treatment of Nicotinamide mononucleotide improved age-related diminished ovary reserve through enhancing the mitophagy level of granulosa cells in mice

J Nutr Biochem. 2022 Mar:101:108911. doi: 10.1016/j.jnutbio.2021.108911. Epub 2021 Nov 19.


Ovarian aging affects the reproductive health of elderly women due to decline in oocyte quality, which is closely related to mitochondrial dysfunction. Nicotinamide mononucleotide (NMN), as a precursor of NAD+, effectively regulate mitochondria metabolism in mice. However, roles of NMN in improving age-related diminished ovary reserve remain to be determined. In present study, 4, 8, 12, 24, 40-week old female ICR mice were collected and a 20-week-long administration of NMN was conducted to 40-week-old mice (60WN), meanwhile the control group is given water (60WC). First, we found that 20-week-long administration of NMN to 40-week-old mice exhibited anti-aging and anti-inflammatory effects on organ structures, along with the improvement of estrus cycle condition and endocrine function. The number of primordial, primary, secondary, antral follicles and corpora luteum of ovaries in 60WN group was significantly increased compared with those in 60WC group. Additionally, the protein and gene expressions of P16 of ovaries were significantly reduced in 60WN group than in 60WC group. the mitochondria biogenesis, autophagy level, and proteases activity enhanced in granulosa cells after 20-week-administration of NMN. Present results indicate that NMN has the potential to save diminished ovary reserve by long-term treatment, providing a basis for exploring the role of NMN in anti-ovarian aging by enhancing the mitophagy level of granulosa cells.

Keywords: Aging; CLPP; LC3B; NMN; Ovary; PGC-1ɑ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Autophagy / drug effects
  • Cathepsin D / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Endopeptidase Clp / metabolism
  • Estrous Cycle / drug effects
  • Female
  • Granulosa Cells / drug effects
  • Granulosa Cells / physiology*
  • Mice
  • Mice, Inbred ICR
  • Mitophagy / drug effects*
  • Nicotinamide Mononucleotide / administration & dosage*
  • Organelle Biogenesis
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / physiology
  • Ovarian Reserve / drug effects*
  • Ovary / drug effects
  • Ovary / metabolism


  • Cyclin-Dependent Kinase Inhibitor p16
  • Nicotinamide Mononucleotide
  • CLPP protein, mouse
  • Endopeptidase Clp
  • Cathepsin D
  • Ctsd protein, mouse