Therapeutic Potential of NAD+ Precursors and Aging-related Diseases

Nicotinamide adenine dinucleotide (NAD+) plays fundamental roles in human life and health as an essential cofactor and substrate for a great number of vital biological processes. A growing body of evidence has demonstrated that the development of many age-related degenerative diseases, including dementia, heart failure, and diabetes, are linked with an age-dependent depletion in cellular NAD+ levels. Preclinical studies have shown that the restoration of NAD+ levels through NAD+ precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) supplementation, reduces the risk of heart failure, ameliorates the manifestations of Alzheimer's and Parkinson's, and improves insulin-sensitivity in type 2 diabetes. In recent years, multiple clinical studies have indicated that NR and NMN supplements are well tolerated and effectively stimulate NAD+ metabolism in healthy subjects. Further efficacy studies of NR and NMN supplements in patients with degenerative diseases are under clinical trial. This article reviews the recent preclinical and clinical progress of NR and NMN supplements as potential therapies to treat aging-related diseases with a focus on cardiovascular disease, neurodegenerative disorders, and diabetes studies.