Table 1.

Hallmarks of Aging Are Key Cellular Changes That Underpin the Cascade of Events that Lead to Systemic Age-Related Decline^*

Hallmark of Aging	Role of NAD+	References
Genomic instability	Adequate NAD+ availability is critical to drive DNA repair enzymes and pathways such as PARP1, SIRT1, and SIRT6	31–33
Cellular senescence	Low NAD+ promotes senescence in skin whilst restoration of NAD+ reduces the burden of senescent cells	40,41
Epigenetic alterations	NAD+-dependent sirtuins are critical for youthful epigenetic regulation. Reduced NAD+ means sirtuins cannot perform this critical role	43
Mitochondrial dysfunction	Adequate NAD+ is critical to healthy mitochondrial function and for the removal of damaged mitochondria	79
Telomere attrition	NAD+ restoration is found to alleviate telomere dysfunction	80
Altered intracellular communication	Low NAD+ promotes age-related inflammation	81
Loss of proteostasis	NAD+ is required for SIRT1-mediated activation of autophagy to clear damaged cellular proteins	60,61
Deregulated nutrient sensing	NAD+ levels are critical to sense the energetic status of the cell for adaptation to energy stress	4
Stem cell exhaustion	NAD+ restoration leads to stem cell rejuvenation	22

^*NAD+ has been identified as a key metabolic intermediate linked to many of the hallmarks of aging.