Reviewing the Aging of the Ovaries
The ovaries, like the thymus, undergo a form of degenerative aging that occurs somewhat in advance of the aging of other parts of the body. It leads to the phenomenon of menopause and subsequent consequences to health and function, which, interestingly, is a feature of aging that is shared with only a few other mammalian species. That makes the ovaries and their surrounding tissues an interesting target for the development of ways to slow or reverse loss of function. Maintained ovarian function may prove to modestly slow aging in older women; it is a reasonable hypothesis and goal to pursue given what is known of the interaction of ovarian aging with other aspects of aging in humans.
Ovarian reserve is essential for fertility and influences healthy aging in women. Advanced maternal age correlates with the progressive loss of both the quantity and quality of oocytes. The molecular mechanisms and various contributing factors underlying ovarian aging have been uncovered.
In this review, we highlight some of critical factors that impact oocyte quantity and quality during aging. Germ cell and follicle reserve at birth determines reproductive lifespan and timing the menopause in female mammals. Accelerated diminishing ovarian reserve leads to premature ovarian aging or insufficiency. Poor oocyte quality with increasing age could result from chromosomal cohesion deterioration and misaligned chromosomes, telomere shortening, DNA damage and associated genetic mutations, oxidative stress, mitochondrial dysfunction, and epigenetic alteration.
We also discuss the intervention strategies to delay ovarian aging. Both the efficacy of senotherapies by antioxidants against reproductive aging and mitochondrial therapy are discussed. Functional oocytes and ovarioids could be rejuvenated from pluripotent stem cells or somatic cells. We propose directions for future interventions. As couples increasingly begin delaying parenthood in life worldwide, understanding the molecular mechanisms during female reproductive aging and potential intervention strategies could benefit women in making earlier choices about their reproductive health.