NAD+ and sirtuins in aging and disease.
Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) 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(+) by supplementing NAD(+) 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(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: imaishin@wustl.edu.
Shin-ichiro
S
Imai
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Glenn Laboratory for the Science of Aging, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: leng@mit.edu.
Leonard
L
Guarente
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm; D004194:Disease; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*
D009243:NAD; D037761:Sirtuins
NAD(+); nicotinamide mononucleotide; nicotinamide phosphoribosyltransferase; nicotinamide riboside; poly-ADP-ribose polymerases; sirtuins