NAD+ and sirtuins in aging and disease

Abstract

Nicotinamide adenine dinucleotide (NAD[superscript +]) is a classical coenzyme mediating many redox reactions. NAD[superscript +] also plays an important role in the regulation of NAD[superscript +]-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD[superscript +] biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD[superscript +] levels decline during the aging process and may be an Achilles’ heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD[superscript +] by supplementing NAD[superscript +] intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD[superscript +] intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.