NAD+ in Aging: Molecular Mechanisms and Translational Implications

The coenzyme NAD(+) is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD(+) levels is important for cells with high energy demands and for proficient neuronal function. NAD(+) depletion is detected in major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, cardiovascular disease and muscle atrophy. Emerging evidence suggests that NAD(+) decrements occur in various tissues during aging, and that physiological and pharmacological interventions bolstering cellular NAD(+) levels might retard aspects of aging and forestall some age-related diseases. Here, we discuss aspects of NAD(+) biosynthesis, together with putative mechanisms of NAD(+) action against aging, including recent preclinical and clinical trials.