Figure 1. Impact of advanced age on hormonal control, testes morphology and function, and sperm production.

In aging men, the hypothalamic-pituitary-testicular (HPT) axis and associated negative-feedback loop is impaired, resulting in an overall hormonal imbalance and diminished testosterone production compared to younger men (1). Altered testicular structure, morphology, and a disruption in spermatogenesis, accompanied by elevated oxidative stress and inflammation, are characteristic of aging testis (2). Aging sperm can also display severe DNA abnormalities and inadequate epigenetic reprogramming (3).