Why NAD+ Declines during Aging: It’s Destroyed


NAD+ is required not only for life but for a long life. In this issue, Camacho-Pereira et al. implicate CD38 in the decline of NAD+ during aging, with implications for combating age-related diseases.

CD38 is a membrane-bound NADase that hydrolyzes NAD+ to nicotinamide and (cyclic-)ADP-ribose. Its protein levels increase during aging, with a corresponding increase in NADase activity and declining NAD+ levels. Mice deficient for CD38 are protected from mitochondrial dysfuntion and diabetes during aging. Many of these effects are mediated through the mitochondrial sirtuin SIRT3. As CD38 also degrades NMN, the CD38 knockout mice also are more sensitive to treatment with NAD+ precursors.