NAD+ and sirtuins in aging and disease

Summary

This comprehensive review in Science examined the evidence linking age-related NAD+ decline to the pathophysiology of aging and age-related diseases through impaired sirtuin function. The review synthesized findings from multiple preclinical studies demonstrating that NAD+ supplementation can restore sirtuin activity and ameliorate age-related metabolic, cardiovascular, and neurodegenerative dysfunction.

Key Findings

• NAD+ levels decline progressively with age in multiple tissues, driven by decreased synthesis (NAMPT expression) and increased consumption by CD38, PARP, and other NAD+-consuming enzymes
• Reduced NAD+ availability impairs sirtuin-mediated deacetylation of key metabolic and stress-response targets, contributing to mitochondrial dysfunction and metabolic disease
• NAD+ repletion strategies (NMN, NR supplementation) restored NAD+ levels and improved metabolic function, insulin sensitivity, and mitochondrial activity in aged animal models