Preclinical and clinical evidence of NAD⁺ precursors in health, disease, and ageing

NAD⁺ is a fundamental molecule in human life and health as it participates in energy metabolism, cell signalling, mitochondrial homeostasis, and in dictating cell survival or death. Emerging evidence from preclinical and human studies indicates an age-dependent reduction of cellular NAD⁺, possibly due to reduced synthesis and increased consumption. In preclinical models, NAD⁺ repletion extends healthspan and / or lifespan and mitigates several conditions, such as premature ageing diseases and neurodegenerative diseases. These findings suggest that NAD⁺ replenishment through NAD⁺ precursors has great potential as a therapeutic target for ageing and age-predisposed diseases, such as Alzheimer's disease. Here, we provide an updated review on the biological activity, safety, and possible side effects of NAD⁺ precursors in preclinical and clinical studies. Major NAD⁺ precursors focused on by this review are nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and the new discovered dihydronicotinamide riboside (NRH). In summary, NAD⁺ precursors have an exciting therapeutic potential for ageing, metabolic and neurodegenerative diseases.