This 2016 review elucidates the synergistic relationship between NAD⁺ and sirtuins in regulating aging and longevity. It details how NAD⁺-dependent sirtuins, particularly SIRT1 and SIRT3, influence metabolic pathways, mitochondrial function, and stress responses. The paper discusses how declining NAD⁺ levels with age impair sirtuin activity, leading to disrupted nuclear-mitochondrial communication