Nicotinamide Riboside Counteracts Testicular Aging: Preclinical Findings

Synopsis

Deleting Qprt, a key enzyme in the NAD+ de novo synthesis pathway and highly expressed in spermatocytes, did not disrupt NAD+ levels or spermatogenesis in young (3-month-old) mice. However, beginning at 6 months, Qprt-deficient males showed a steep age-related decline in testicular NAD+, accompanied by germ cell loss, increased apoptosis, mitochondrial dysfunction, impaired meiotic prophase I progression, defective double-strand break repair, and abnormal meiotic sex chromosome inactivation. Supplementation with nicotinamide riboside (NR) restored NAD+ levels and rescued these spermatogenic defects. These findings demonstrate that NAD+ de novo synthesis becomes essential with age to maintain meiotic integrity, mitochondrial health, and germ cell survival, and that NR is an effective therapeutic strategy to counteract age-related reproductive decline caused by NAD+ deficiency.

Journal

Aging Cell