Roles of NAD⁺ in Health and Aging

NAD⁺, the essential metabolite involved in multiple reactions such as the regulation of cellular metabolism, energy production, DNA repair, mitophagy and autophagy, inflammation, and neuronal function, has been the subject of intense research in the field of aging and disease over the last decade. NAD⁺ levels decline with aging and in some age-related diseases, and reduction in NAD⁺ affects all the hallmarks of aging. Here, we present an overview of the discovery of NAD⁺, the cellular pathways of producing and consuming NAD⁺, and discuss how imbalances in the production rate and cellular request of NAD⁺ likely contribute to aging and age-related diseases including neurodegeneration. Preclinical studies have revealed great potential for NAD⁺ precursors in promotion of healthy aging and improvement of neurodegeneration. This has led to the initiation of several clinical trials with NAD⁺ precursors to treat accelerated aging, age-associated dysfunctions, and diseases including Alzheimer's and Parkinson's. NAD supplementation has great future potential clinically, and these studies will also provide insight into the mechanisms of aging.