Metabolism in Male Reproductive Aging

Abstract

Similar to female reproductive health, male reproductive health declines with increasing age, albeit in a more gradual way. In the US, the average age of first-time fathers has been steadily increasing since 1980. This is concerning because increasing paternal age is positively correlated with reduced sperm chromatin quality and higher numbers of DNA strand breaks (DNA sb), which negatively affects pregnancy outcome and child development. While underlying reasons are not well understood, one of the well-known hallmarks of aging is a significant decline of body nicotinamide adenine dinucleotide (NAD) levels. We propose that low body-wide NAD levels provide a plausible explanation for metabolic alterations that are associated with declining hormonal production and testicular volume, as well as reduced sperm quality in aging men.

Keywords: DNA integrity; aging; chromatin; developmental origin of health and disease (DOHaD); nicotinamide adenine dinucleotide (NAD); redox stress; reproductive health; sperm; testis; testosterone.

Figure 1.. Link between NAD and reproductive health.

The availability of NAD determines how active cellular redox enzymes and epigenetic modifiers like PARPs and sirtuins can be, which in turn regulates cellular redox balance, DNA repair capability, chromatin organization and inflammation. In the context of reproductive health, declining NAD availability during aging thus can negatively affect hormonal control and germ cell quality, and ultimately results in diminished reproductive fitness and offspring health.