NAD⁺ Biology in Aging and Chronic Disease: Mechanisms and Evidence Across Skin, Fertility, Osteoarthritis, Hearing and Vision Loss, Gut Health, Cardiovascular-Hepatic Metabolism, Neurological Disorders, and Muscle

Nicotinamide adenine dinucleotide (NAD⁺) is crucial for energy metabolism, DNA repair, and cellular stress resilience, with declines linked to aging and chronic diseases. This review highlights the potential of NAD⁺ restoration to influence disease biology across various organ systems. NAD⁺ supports key metabolic processes and acts as a substrate for DNA repair and mitochondrial function. Impaired NAD⁺ homeostasis is associated with mitochondrial dysfunction and immune responses in conditions like neurodegeneration and cardiometabolic disease. While NAD⁺ precursor supplementation shows promise in elevating NAD⁺ levels, clinical outcomes are inconsistent, and evidence for intravenous NAD⁺ therapy is limited. Well-designed human studies are needed to confirm the clinical benefits of NAD⁺-boosting strategies across multiple health conditions.