Therapeutic approaches to increase cellular NAD+ levels. The three major pathways for the biosynthesis of NAD+ are shown. Approaches to increase NAD+ levels include administering the metabolites, NA, NR, or NMN to increase their levels or increasing NAMPT activity (up arrowheads). In addition, down-regulation (down arrowhead) of the NAD+ consumers, PARP and CD38/157, will result in increased cellular NAD+ levels. The increased NAD+ levels will increase the levels and activity of NAD+-dependent SIRT1 and other sirtuins with beneficial metabolic outcomes.