NAD ⁺ biosynthesis, aging, and disease

Nicotinamide adenine dinucleotide (NAD ⁺) biosynthesis and its regulation have recently been attracting markedly increasing interest. Aging is marked by a systemic decrease in NAD ⁺ across multiple tissues. The dysfunction of NAD ⁺ biosynthesis plays a critical role in the pathophysiologies of multiple diseases, including age-associated metabolic disorders, neurodegenerative diseases, and mental disorders. As downstream effectors, NAD ⁺-dependent enzymes, such as sirtuins, are involved in the progression of such disorders. These recent studies implicate NAD ⁺ biosynthesis as a potential target for preventing and treating age-associated diseases. Indeed, new studies have demonstrated the therapeutic potential of supplementing NAD ⁺ intermediates, such as nicotinamide mononucleotide and nicotinamide riboside, providing a proof of concept for the development of an effective anti-aging intervention.