NAD+ and sirtuins in aging and disease
Author(s)Imai, Shin-ichiro; Guarente, Leonard Pershing
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology
Trends in Cell Biology
Imai, Shin-ichiro, and Leonard Guarente. “NAD+ and Sirtuins in Aging and Disease.” Trends in Cell Biology 24.8 (2014): 464–471.
Author's final manuscript