Restoring NAD⁺-Sirtuins Signaling: A Novel Approach to Combat Male Reproductive Aging - PubMed
a day ago
- #Therapeutic strategies
- #Male reproductive aging
- #NAD-Sirtuins axis
- Male reproductive aging involves declines in testosterone synthesis, spermatogenic efficiency, and fertility due to multi-system dysfunction.
- The NAD��-Sirtuins axis is a central regulator of testicular homeostasis, with its dysregulation contributing to aging-related issues.
- NAD�� depletion affects energy metabolism, antioxidant defenses, and steroidogenesis, while reduced Sirtuins activity disrupts spermatogonial stem cell maintenance and blood-testis barrier integrity.
- Key pathological features include structural compromise, metabolic-oxidative stress, chronic inflammation, epigenetic dysregulation, and hormonal synthesis disorder.
- Interventions like NAD�� precursors (NMN/NR), Sirtuin activators (resveratrol/quercetin), and lifestyle strategies (intermittent fasting/exercise) show efficacy in preclinical models.
- NMN supplementation has been shown to restore sperm quality and testosterone synthesis, while resveratrol reduces sperm DNA fragmentation.
- Critical knowledge gaps remain regarding tissue-specific Sirtuin functions, long-term safety of NAD�� boosters, and individualized intervention protocols.
- Future research should focus on testicular-targeted delivery systems, NAD��-based biomarkers, and randomized trials.