Nicotinamide Adenine Nucleotide-The Fountain of Youth to Prevent Oocyte Aging?

Abstract

According to the U.S. Special Operations Command (SOCOM), new clinical trials of an anti-aging oral treatment using nicotinamide adenine nucleotide are planned for 2022. All over the globe, the discovery of the fountain of youth is still a great goal to reach, not only among aging researchers, since people desire to stay longer healthy and feel young when reaching old age. Since the 1960s, women delaying pregnancy to pursue higher educational levels and a career path has contributed to drastically diminished overall female fertility rates (e.g., number of born offspring/woman). Consequently, a growing number of advanced-aged women depend on assisted reproductive technologies (ART) to become pregnant. In 2019, the Society for Assisted Reproductive Technology reported 293,672 cycles for oocyte retrieval. This change of demographics influenced women's age of having their first child, which has increased significantly. However, their reproductive tract shows hallmarks of aging very early in life without an effective preventive treatment. Therefore, we will present whether NAD+ could help to prevent oocyte aging.

Keywords: NAD+; aging; nicotinamide adenine nucleotide; oocyte; sirtuins.

Figure 1

Impact of aging on NAD+ levels and oocyte number, and oocyte quality. (A) The blue line in the graph shows the gradual decline of the follicular pool, which is more enhanced after the age of 35 years in women. The oocytes in theses follicles are arrested in Prophase of the first meiotic division, and with advancing maternal age, oocytes’ mitochondria lose their function more and more. In consequence, NAD is less available, the oocyte has reduced quality and difficulties to defend against ROS. Sirt1 uses NAD+ as co-factor during the deacetylation of acetylated proteins. During this process nicotinamide is produced, which is then recycled back into NAD+. (B) Scheme showing the involvement of NADH/NAD+ in the electron transport chain which transports electrons along the mitochondrial membrane through the single complexes (I–IV). Abbreviations: ADP = adenosine diphosphate, ATP = adenosine triphosphate, CoQ = co-enzyme Q, Cyt c = cytochrome c, NAM = nicotinamide, NMN = nicotinamide mononucleotide, NAMPT= nicotinamide phosphoribosyl-transferase, NNMAT = nicotinamide mononucleotide adenylyl-transferase.

Figure 1

Impact of aging on NAD+ levels and oocyte number, and oocyte quality. (A) The blue line in the graph shows the gradual decline of the follicular pool, which is more enhanced after the age of 35 years in women. The oocytes in theses follicles are arrested in Prophase of the first meiotic division, and with advancing maternal age, oocytes’ mitochondria lose their function more and more. In consequence, NAD is less available, the oocyte has reduced quality and difficulties to defend against ROS. Sirt1 uses NAD+ as co-factor during the deacetylation of acetylated proteins. During this process nicotinamide is produced, which is then recycled back into NAD+. (B) Scheme showing the involvement of NADH/NAD+ in the electron transport chain which transports electrons along the mitochondrial membrane through the single complexes (I–IV). Abbreviations: ADP = adenosine diphosphate, ATP = adenosine triphosphate, CoQ = co-enzyme Q, Cyt c = cytochrome c, NAM = nicotinamide, NMN = nicotinamide mononucleotide, NAMPT= nicotinamide phosphoribosyl-transferase, NNMAT = nicotinamide mononucleotide adenylyl-transferase.