NAD+

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme present in all living cells, serving as a critical cofactor for hundreds of enzymatic reactions including those central to energy metabolism, DNA repair, and epigenetic regulation. The age-related decline in NAD+ levels has emerged as a fundamental mechanism of biological aging.

As a coenzyme, NAD+ participates in redox reactions as an electron carrier (NAD+/NADH), but its non-redox functions have attracted intense research interest. NAD+ is consumed as a substrate by sirtuins (SIRT1-7), which deacetylate proteins to regulate metabolism, stress responses, and longevity pathways. It is also consumed by PARP enzymes during DNA repair and by CD38 in immune signaling.

NAD+ levels decline with age due to reduced synthesis and increased consumption by CD38 and other NADases. This decline impairs sirtuin and PARP function, contributing to metabolic dysfunction, genomic instability, and mitochondrial deterioration - key hallmarks of aging.

Research strategies to restore NAD+ include direct supplementation, precursor supplementation (NMN, NR), CD38 inhibition, and NNMT inhibition. Direct NAD+ supplementation faces challenges of poor oral bioavailability and cellular uptake, driving interest in precursors and alternative approaches to elevating intracellular NAD+.